Tandem Enyne Allene-Radical Cyclization: Low-Temperature Approaches to Benz[e]indene and Indene Compounds

Article abstract of DOI:10.1021/jo961049j

In an effort to lower the temperatures required to prepare multicyclic compounds using the tandem enediyne-radical cyclization, we have developed the tandem enyne allene-radical cyclization which proceeds at temperatures as low as 37°C. The reactions were

Full text of DOI:10.1021/jo961049j

J . Org. Chem. 1997, 62, 603-626
603
Ta n d em En yn e Allen e-Ra d ica l Cycliza tion : Low -Tem p er a tu r e
Ap p r oa ch es to Ben z[e]in d en e a n d In d en e Com p ou n d s
J anet Wisniewski Grissom,* Detlef Klingberg, Dahai Huang, and Brian J . Slattery
Department of Chemistry, University of Utah, Salt Lake City, Utah 84112
Received J une 4, 1996 (Revised Manuscript Received November 22, 1996X)
In an effort to lower the temperatures required to prepare multicyclic compounds using the tandem
enediyne-radical cyclization, we have developed the tandem enyne allene-radical cyclization which
proceeds at temperatures as low as 37 °C. The reactions were carried out using three different
methods for the preparation of the enyne allenes. The first method involved the [3,3] sigmatropic
rearrangement of an enediyne followed by a tandem enyne allene-radical cyclization. This reaction
could be effected either by thermolysis (150 °C) or by AgBF4 rearrangement followed by heating at
75 °C. A second technique utilized a [2,3] sigmatropic shift of an enediyne at -78 °C followed by
tandem cyclization at 37 or 75 °C depending on the substrate. The final method involved the base-
catalyzed isomerization of propargyl sulfones which yielded enyne allenes that underwent cyclization
at 37 °C. These three sequences provide a method for the synthesis of ring systems using conditions
that may be compatible with the sensitive functionality needed during the synthesis of complex
natural products.
In tr od u ction
less attention has been focused on utilizing these highly
reactive intermediates in subsequent radical cycli-
In recent years, the enediyne antitumor antibiotics1
have been widely investigated due to their unique mech-
anism of DNA-cleavage and their unusual structures.
Moreover, the emergence of these naturally occurring,
biologically active compounds has sparked extensive
investigations in the chemistry of conjugated enediynes,1-3
enyne allenes1,4,5 and enyne ketenes.1,6 While consider-
able effort has been devoted to the DNA-cleaving ability
of the biradical intermediates that arise from these
compound families by a cycloaromatization reaction,1-6
zations.1ab,7,8
Previously, we have reported that benz[e]indene de-
rivatives can be synthesized in excellent yields via a
tandem enediyne-radical cyclization of aromatic ene-
diynes (Figure 1).7 With this strategy, aromatic enediyne
1 can be converted into benz[e]indene derivative 2 in very
high yield. The corresponding nonaromatic enediynes
also undergo a similar cyclization to provide indene
derivatives;7c however, the yields are only moderate. The
allylic enediyne alcohol 3, for instance, provides indan
system 4 in 54% yield when heated in 1,2-dichloroben-
zene at 230 °C in the presence of 1,4-cyclohexadiene.
Moreover, we have demonstrated that both radicals
formed in the Bergman cyclization of enediyne substrates
can be utilized in subsequent radical cyclizations. The
thermolysis of enediyne compound 5 carrying two radical-
X Abstract published in Advance ACS Abstracts, J anuary 1, 1997.
(1) For reviews of the enediyne antitumor antibiotics and general
enediyne chemistry, see: (a) Grissom, J . W.; Gunawardena, G. U.;
Klingberg, D.; Huang, D. Tetrahedron. 1996, 52, 6453. (b) Wang, K.
K. Chem. Rev. 1996, 96, 207. (c) Danishefsky, S. J .; Shair, M. D. J .
Org. Chem. 1996, 61, 16. (d) Pratviel, G.; Bernadou, J .; Meunier, B.
Angew. Chem., Int. Ed. Engl. 1995, 34, 746. (e) Maier, M. E. Synlett
1995, 13. (f) Hirama, M. J . Synth. Org. Chem. J pn. 1994, 52, 980. (g)
Maier, M. E. Kontakte 1994, 3. (h) Thebtaranonth, C.; Thebtaranonth,
Y. Cyclization Reactions, CRC Press: Boca Raton, FL, 1994. (i)
Nicolaou, K. C. Chem. Brit. 1994, 30, 33. (j) Nicolaou, K. C. Angew.
Chem., Int. Ed. Engl. 1993, 32, 1377. (k) Nicolaou, K. C.; Smith, A. L.;
Yue, E. W. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 5881. (l) Nicolaou,
K. C.; Smith, A. L. Pure Appl. Chem. 1993, 65, 1271. (m) Hoffman, R.
American Scientist 1993, 81, 324. (n) Hirama, M. Recent Progress in
the Chemical Synthesis of Antibiotics and Related Microbial Products;
Lukacs, G., Ed.; Springer-Verlag: Berlin, 1993; Vol. 2. (o) Skrydstrup,
T.; Ulibarri, G.; Audrain, H.; Grierson, D., ref 1n. (p) Gleiter, R.; Kratz,
D. Angew. Chem., Int. Ed. Engl. 1993, 32, 842. (q) Nicolaou, K. C.;
Dai, W.-M.; Tsay, S.-C.; Estevez, V. A.; Wrasidlo, W. Science 1992, 256,
1172. (r) Nicolaou, K. C.; Smith, A. L. Acc. Chem. Res. 1992, 25, 497.
(s) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed. Engl. 1991, 30,
1387. (t) Lee, M. D.; Ellestad, G. A.; Borders, D. B. Acc. Chem. Res.
1991, 24, 235. (u) Goldberg, I. H. Acc. Chem. Res. 1991, 24, 191. (v)
Waldmann, H. Nachr. Chem. Tech. Lab. 1991, 39, 211.
(2) (a) J ones, R. R.; Bergman, R. G. J . Am. Chem. Soc. 1972, 94,
660. (b) Bergman, R. G. Acc. Chem. Res. 1973, 6, 25. (c) Lockhart, T.
P.; Mallon, C. B.; Bergman, R. G. J . Am. Chem. Soc. 1980, 102, 5976.
(d) Lockhart, T. P.; Comita, P. B.; Bergman, R. G. J . Am. Chem. Soc.
1981, 103, 4082. (e) Lockhart, T. P.; Bergman, R. G. J . Am. Chem.
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Bergman, R. G. J . Am. Chem. Soc. 1992, 114, 3120.
(3) For the most recent references on enediyne chemistry, see: (a)
de Arau´jo, M. A.; Comasseto, J . V. Synlett 1995, 1145. (b) Ko¨nig, B.;
Hollnagel, H.; Ahrens, B.; J ones, P. G. Angew. Chem., Int. Ed. Engl.
1995, 34, 2538. (c) Banfi, L.; Guanti, G. Angew. Chem., Int. Ed. Engl.
1995, 34, 2393.
(5) For recent references on enyne allene chemistry, see: (a)
Shibuya, M.; Wakayama, M.; Naoe, Y.; Kawakami, T.; Ishigaki, K.;
Nemoto, H.; Shimizu, H.; Nagao, Y. Tetrahedron Lett. 1996, 37, 865.
(b) Krause, N.; Hohmann, M. Synlett 1996, 89. (c) Gillmann, T.; Hu¨lsen,
T.; Massa, W.; Wocadlo, S. Synlett 1995, 1257. (d) Schmittel, M.;
Strittmatter, M.; Kiau, S. Tetrahedron Lett. 1995, 36, 4975.
(6) For examples of enyne ketene cyclizations, see: (a) Xiong, Y.;
Xia, H.; Moore, H. W. J . Org. Chem. 1995, 60, 6460. (b) Sullivan, R.
W.; Coghlan, V. M.; Munk, S. A.; Reed, M. W.; Moore, H. W. J . Org.
Chem. 1994, 59, 2276. (c) Nakatani, K.; Isoe, S.; Maekawa, S.; Saito,
I. Tetrahedron Lett. 1994, 35, 605. (d) Padwa, A.; Chiacchio, U.; Fairfax,
D. J .; Kassir, J . M.; Litrico, A.; Semones, M. A.; Xu, S. L. J . Org. Chem.
1993, 58, 6429. (e) Padwa, A.; Austin, D. J .; Chiacchio, U.; Kassir, J .
M.; Rescifina, A.; Xu, S. L. Tetrahedron Lett. 1991, 32, 5923.
(7) (a) Grissom, J . W.; Calkins, T. L. Tetrahedron Lett. 1992, 33,
2315. (b) Grissom, J . W.; Calkins, T. L.; Egan, M. L. J . Am. Chem.
Soc. 1993, 115, 11744. (c) Grissom, J . W.; Calkins, T. L.; McMillen, H.
A. J . Org. Chem. 1993, 58, 6556. (d) Grissom, J . W.; Klingberg, D. J .
Org. Chem. 1993, 58, 6559. (e) Grissom, J . W.; Calkins, T. L. J . Org.
Chem. 1993, 58, 5422. (f) Grissom, J . W.; Calkins, T. L.; Huang, D.;
McMillen, H. A. Tetrahedron 1994, 50, 4635. (g) Grissom, J . W.;
Calkins, T. L.; McMillen, H. A.; J iang, Y. J . Org. Chem. 1994, 59, 5833.
(h) Grissom, J . W.; Klingberg, D.; Meyenburg, S.; Stallman, B. L. J .
Org. Chem. 1994, 59, 7876.
(8) (a) Wang, K. K.; Andemichael, Y. W.; Gu, Y. G. J . Org. Chem.
1992, 57, 794. (b) Wang, K. K.; Andemichael, Y. W.; Huang, Y. J . Org.
Chem. 1993, 58, 1651. (c) Moore, H. W.; Ezcurra, J . E.; Pham, C. J .
Org. Chem. 1992, 57, 4787. (d) Xu, S. L.; Taing, M.; Moore, H. W. J .
Org. Chem. 1991, 56, 6104. (e) Moore, H. W.; Xia, H. J . Org. Chem.
1992, 57, 3765. (f) Moore, H. W.; Xu, S. L. J . Org. Chem. 1992, 57,
326. (g) Reference 6c.
(4) (a) Myers, A. G.; Dragovich, P. S. J . Am. Chem. Soc. 1989, 111,
9130. (b) Myers, A. G.; Kuo, E. Y.; Finney, N. S. J . Am. Chem. Soc.
1989, 111, 8057. (c) Myers, A. G.; Dragovich, P. S.; Kuo, E. Y. J . Am.
Chem. Soc. 1992, 114, 9369.
S0022-3263(96)01049-3 CCC: $14.00 © 1997 American Chemical Society

604 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
Sch em e 1
for the preparation of enyne allene substrates to be used
in tandem enyne allene-radical cyclizations was based
on the well-precedented conversion of propargyl vinyl
ethers into allenes by using a [3,3] sigmatropic rear-
rangement.11 In order to utilize this strategy toward the
synthesis of enyne allene substrates, various different
enediyne vinyl ethers were synthesized.
F igu r e 1.
accepting tethers leads to the simultaneous formation of
three rings providing the tetracyclic naphthalene system
6 in 99% yield (Figure 1). Both the tandem enediyne-
radical cyclization and the tandem enediyne-bis-radical
cyclization methodologies require very high temperatures
(ca. 170-230 °C); thus applications toward the synthesis
of more complex systems have proven difficult. In fact,
efforts in our laboratory to utilize the tandem enediyne-
radical cyclization strategy for the synthesis of steroidal
systems have resulted in decomposition of the precursor
enediynes.9
In contrast to the high-temperature tandem enediyne-
radical cyclization that uses the Bergman cyclization as
the initial ring-closing step, the combination of an enyne
allene cyclization4 (Myers cyclization) with a subsequent
radical cyclization would allow the construction of the
same benz[e]indene framework under much milder con-
ditions, since the Myers cyclization typically proceeds at
temperatures significantly lower than those required for
the related Bergman cyclization.
Scheme 1 outlines the synthetic approaches for the
preparation of the enediyne vinyl ethers 9 and 12, which
were both synthesized from 1,2-diiodobenzene (7).
A
palladium(0)-catalyzed coupling reaction under modified
Castro-Stephens conditions12 with propargyl alcohol in
the presence of bis(triphenylphosphine)palladium(II) chlo-
ride and copper(I) iodide as well as triethylamine as a
base gave rise to iodoarene 8. Compound 8 was con-
verted into a vinyl ether using mercury(II) acetate and
ethyl vinyl ether at 40 °C, followed by a second pal-
ladium(0)-catalyzed coupling reaction with (trimethylsi-
lyl)acetylene under the same conditions as outlined
above, and a desilylation with potassium carbonate in
methanol,13 to provide enediyne vinyl ether 9 in a total
yield of 35% over four steps.
The synthetic sequence for the preparation of enediyne
vinyl ether 12 started with a palladium(0)-catalyzed
coupling reaction of 1,2-diiodobenzene with 4-pentynol
(Scheme 1). Alcohol 10 arising from the coupling reaction
was oxidized using pyridinium chlorochromate (PCC)14
and the resulting aldehyde converted into the unsatur-
ated ester 11 by a Horner-Emmons reaction under
In line with our efforts to lower the temperature to
effect the formation of the benz[e]indene system, we have
successfully developed the tandem enyne allene-radical
cyclization strategy, using three independent synthetic
methods for the preparation of the cyclization precursors.
This methodology, which utilizes the enyne allene cy-
clization as the initial ring closure step, provides benz-
[e]indene products at temperatures as low as 37 °C.
(11) (a) Lutz, R. P. Chem. Rev. 1984, 84, 205. (b) Viola, A.; Collins,
J . J .; Filipp, N. Tetrahedron 1981, 37, 3765. (c) Bennett, G. B. Synthesis
1977, 589. (d) For a recent example of a [3,3] sigmatropic rearrange-
ment for the formation of an allene at ambient temperature, see:
Harusawa, S.; Moriyama, H.; Kase, N.; Ohishi, H.; Yoneda, R.;
Kurihara, T. Tetrahedron 1995, 51, 6475.
Ta n d em En yn e Allen e-Ra d ica l Cycliza tion via
[3,3] Sigm a tr op ic Rea r r a n gem en ts10
(12) (a) Singh, R.; J ust, G. Tetrahedron Lett. 1990, 31, 185. (b)
Guillerm, D.; Linstrumelle, G. Tetrahedron Lett. 1985, 26, 3811. (c)
Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467.
(d) For the original Castro-Stephens conditions, see: Castro, C. E.;
Stephens, R. D. J . Org. Chem. 1963, 28, 2163.
Syn th esis of th e P r ecu r sor s for th e Ta n d em
En yn e Allen e-Ra d ica l Cycliza tion via [3,3] Sigm a -
tr op ic Rea r r a n gem en ts. The first method we chose
(13) (a) Hurst, D. T.; McInnes, A. G. Can. J . Chem. 1965, 43, 2004.
(b) McInnes, A. G. Can. J . Chem. 1965, 43, 1998.
(14) Corey, E. J .; Suggs, J . W. Tetrahedron Lett. 1975, 2647.
(9) Grissom, J . W.; Calkins, T. L. Unpublished results.
(10) Grissom, J . W.; Huang, D. J . Org. Chem. 1994, 59, 5114.

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 605
Sch em e 2
Sch em e 3
Roush-Masamune conditions15 using trimethyl phospho-
noacetate in the presence of lithium chloride and 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) in acetonitrile. A
subsequent palladium(0)-catalyzed coupling reaction with
propargyl alcohol and conversion of the resulting alkynol
into a vinyl ether completed the preparation of enediyne
compound 12 in a total yield of 25% over five steps.
Alcohol 14 served as a key intermediate for the
preparation of the precursor diynes 15 and 17 (Scheme
2). Alcohol 14 was prepared from 2-iodobenzyl alcohol
(13) via oxidation with PCC and treatment of the
resulting aldehyde with lithiated tert-butyldimethylsilyl
propargyl ether in tetrahydrofuran (THF) at -20 °C
(78%). Diyne 15 was obtained in a total yield of 35% from
substrate 14 using a palladium(0)-catalyzed reaction with
(trimethylsilyl)acetylene, followed by conversion of the
alcohol into a vinyl ether and base-catalyzed desilylation
of the (trimethylsilyl)acetylene subunit. Diyne vinyl
ether 17 was obtained from intermediate 14 in a se-
quence of six steps (Scheme 2). The hydroxyl group of
14 was acetylated with acetic anhydride in the presence
of triethylamine, followed by a palladium(0)-catalyzed
coupling reaction with 4-pentynol to give alcohol 16.
Subsequent conversion of the primary alcohol into an R,â-
unsaturated ester using oxidation with PCC and a
Horner-Emmons reaction of the resulting aldehyde gave
vinyl ether 17 (overall yield 10% from 14).
Resu lts of th e [3,3] Sigm a tr op ic Rea r r a n gem en t-
Med ia ted Ta n d em En yn e Allen e-Ra d ica l Cycliza -
tion Exp er im en ts. Mild thermolysis of enediyne vinyl
ether 9 at 150 °C in chlorobenzene in the presence of 1,4-
cyclohexadiene (1,4-CHD) as a hydrogen atom donor
produced aldehyde 20 and the tricyclic ether 23 as a 3:1
mixture in a combined yield of 56% (Scheme 3). The
formation of the two products can be rationalized by two
competing mechanistic pathways. The major pathway
presumably involves the initial formation of enyne allene
18 via a [3,3] sigmatropic rearrangement followed by an
enyne allene cyclization to form biradical 19 and hydro-
gen abstraction from 1,4-CHD to produce aldehyde 20.
The minor pathway does not involve a [3,3] sigmatropic
shift, but instead proceeds through a tandem enediyne-
radical cyclization to form the biradical 21, which un-
dergoes a 5-exo ring closure and hydrogen abstraction to
give the tricyclic ether 23. It is interesting that the
tandem enediyne-radical cyclization proceeded at 150
°C since most of our earlier studies failed to reveal
significant reactivity at this temperature.
The thermal cyclization of enediyne 12 containing a
pendent olefin as a radical-accepting tether was then
investigated in order to test the feasibility of the tandem
enyne allene-radical cyclization strategy. When precur-
sor 12 was heated to 150 °C in the presence of 1,4-CHD,
benz[e]indenyl aldehyde 25 was isolated as the only
characterizable product in about 20% yield (Scheme 4).
Mechanistically, this aldehyde presumably arises from
a [3,3] sigmatropic rearrangement of aromatic enediyne
12 to give intermediate 24 immediately followed by an
enyne allene cyclization, a 5-exo radical cyclization of the
resulting aryl radical, and hydrogen abstraction from 1,4-
CHD. There was no evidence for the formation of the
tetracyclic ether 27 arising from a tandem enediyne-
radical cyclization. This observation is consistent with
the fact that the thermal activation energy for the
cyclization of o-arene enediynes containing two acetylenic
tethers (Ea ) 34.0 ( 0.3 kcal/mol) is substantially higher
than that for the corresponding o-arene enediyne with
only one acetylenic tether (Ea ) 28.1 ( 0.8 kcal/mol), as
determined in our laboratory.7c
In an attempt to improve the yield of this reaction and
to reduce the severity of the reaction conditions, we tried
to effect the sigmatropic rearrangement at a lower
temperature by reacting enediyne 12 with a catalytic
amount of silver(I) tetrafluoroborate (AgBF4)11 in benzene
at room temperature to produce enyne allene 24. How-
ever, 24 could not be isolated due to its slow decomposi-
tion and its propensity to undergo isomerization to the
(15) Blanchette, M. A.; Choy, W.; Davis, J . T.; Essenfeld, A. P.;
Masamune, S.; Roush, W. R.; Sakai, T. Tetrahedron Lett. 1984, 25,
2183.

606 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
Sch em e 4
Sch em e 5
Sch em e 6
unstable R,â-unsaturated aldehyde 26. Attempts were
made to prevent the isomerization of 24 to 26 by reducing
the aldehyde of 24 to the primary alcohol using sodium
borohydride (NaBH4). Unfortunately, the subsequent
enyne allene cyclizations did not work well and produced
a complex mixture of products along with a trace of the
desired cyclization product. Thermolysis of the crude
product 24 at 75 °C in the presence of 1,4-CHD provided
only a small amount of the desired tandem enyne allene-
radical cyclization product 25 in 10% yield along with
aldehyde 26 and unidentified decomposition products
(Scheme 4). Although the cyclization of precursor 12
provides evidence for the tandem enyne allene-radical
cyclization, the modest yield of the desired benzindene
25 fails to demonstrate this method as a viable alterna-
tive to the high-temperature tandem enediyne-radical
cyclization strategy.
Previous work by Myers has shown that a simple alkyl
substitution at the C-3 position of an allene (cf. Scheme
4) accelerates the enyne allene cyclization reaction.4 The
results of the enyne allene cyclization of substrate 24 and
some other results in our laboratory, which will be
discussed shortly, suggest that there might be an unfa-
vorable interaction between the C-1 substituent at the
allene and the ortho hydrogen of the aryl ring of the
enyne allene; this interaction might be the origin of the
low yields of the transformations described above. To test
this theory, aromatic diyne 15 was prepared so that the
[3,3] sigmatropic rearrangement would place the sub-
stituent in the sterically less demanding C-3 position of
resulting allene 28 (Scheme 5).
When diyne 15 was heated to 150 °C in chlorobenzene
in the presence of 1,4-CHD, naphthalene derivative 30
was obtained in 45% isolated yield (Scheme 5). Product
30 most likely arises from a [3,3] sigmatropic rearrange-
ment of propargyl vinyl ether 15 followed by an enyne
allene cyclization of intermediate 28 to form biradical 29,
which abstracts hydrogen from 1,4-CHD. Unfortunately,
the silver(I)-catalyzed [3,3] sigmatropic shift of 15 was
unsuccessful presumably due to the presence of the
terminal acetylene hydrogen.
Due to the success of the tandem [3,3] sigmatropic
rearrangement-enyne allene cyclization of 15, attention
was then focused on diyne 17 in order to test whether a
pendent olefin would trap the aromatic radical generated
from the enyne allene cyclization (Scheme 6). When 17
was thermolyzed at 150 °C, 2,3-dihydrobenz[e]indene
derivatives 33a and 33b were isolated as a 1:1 diaster-
eomeric ratio in a combined yield of 54% (Scheme 6). The
reaction proceeds through a [3,3] sigmatropic rearrange-
ment of 17 to give enyne allene intermediate 31, which
immediately undergoes an enyne allene cyclization to
afford biradical 32. The aryl radical within 32 then
undergoes a 5-exo radical cyclization followed by hydro-
gen abstraction from 1,4-CHD to yield tricyclic com-
pounds 33a and 33b.
In an effort to carry out the enyne allene-radical
cyclization at lower temperature, diyne 17 was treated
with a catalytic amount of AgBF4 at room temperature
to afford enyne allene intermediate 31 in 98% yield by a
Lewis acid-catalyzed [3,3] sigmatropic rearrangement.
The thermolysis of compound 31 at 75 °C in chloroben-
zene in the presence of 1,4-CHD led to the formation of
2,3-dihydrobenz[e]indene derivatives 33a and 33b (1:1

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 607
Sch em e 7
ratio) in an excellent combined yield of 80% (Scheme 6).
In addition to the reaction temperature being kept
relatively low, the yield is improved over the one-step
thermal conversion of 17 to 33, which had to be per-
formed at 150 °C. It is significant that dihydrobenz[e]-
indene derivatives 33a and 33b were formed at 75 °C
while similar compounds constructed from a tandem
enediyne-radical cyclization required 190 °C or above.7
Although the enediyne cyclizations occur in high yield,
certain functional groups do not survive such high
temperatures. The lower temperature employed for the
enyne allene cyclization is likely to be compatible with
sensitive functionality that would be required in the
synthesis of a complex natural product.
These results identify the tandem enyne allene-radical
cyclization as a suitable alternative to the tandem
enediyne-radical cyclization methodology for the con-
struction of molecules with a benz[e]indene framework.
This new method is comparatively efficient, and the
reaction temperatures are much more desirable for the
synthetic chemist.
Ta n d em En yn e Allen e-Ra d ica l Cycliza tion via
[2,3] Sigm a tr op ic Rea r r a n gem en ts.16
Syn th esis of P r ecu r sor s for th e Ta n d em En yn e
Allen e-Ra d ica l Cycliza tion of Ar om a tic En yn e Al-
len es via [2,3] Sigm a tr op ic Rea r r a n gem en t. Enyne
allenes that undergo Myers cyclization have been previ-
ously synthesized via a [2,3] sigmatropic rearrangement
of phosphinites and sulfinates.17 To establish if this
method of allene formation would be applicable to the
synthesis of suitable precursors for the tandem enyne
allene-radical cyclization, a set of diyne alcohols was
synthesized as outlined in Scheme 7. Due to the lability
of the sulfoxides as described by Nicolaou, we chose the
phosphine oxides for initial investigation.
Diyne substrate 34 was obtained in 89% yield from the
iodophenyl compound 14 by a palladium(0)-catalyzed
coupling reaction with (trimethylsilyl)acetylene and sub-
sequent desilylation with potassium carbonate in metha-
nol. Pentynol derivative 16 was oxidized using PCC and
the resulting aldehyde subjected to a Horner-Emmons
reaction under Roush-Masamune conditions with tri-
methyl phosphonoacetate in acetonitrile in the presence
of lithium chloride and DBU. A subsequent base-
catalyzed cleavage of the acetate provided precursor 35
in a combined yield of 59% over three steps. 3-(2-
Iodophenyl)-2-propyn-1-ol (8) was converted to enediyne
alcohol 36 in 96% yield by a palladium(0)-catalyzed
coupling/desilylation sequence as described above for
substrate 34. A palladium(0)-catalyzed coupling reaction
with propargyl alcohol was used to afford enediyne 37
in 88% yield from iodophenyl compound 11.
Sch em e 8
Resu lts of th e [2,3] Sigm a tr op ic Rea r r a n gem en t-
Med ia ted Ta n d em En yn e Allen e-Ra d ica l Cycliza -
tion Exp er im en ts In volvin g Ar om a tic En yn e Allen e
Su bstr a tes. In analogy to the successful cyclizations of
substrates 28 and 31 in the experiments involving [3,3]
sigmatropic rearrangements (cf. Schemes 5 and 6), the
cyclization behavior of compounds 38 and 41 was inves-
tigated. Diyne alcohol 34 was treated with chlorodiphen-
ylphosphine in THF at -78 °C in the presence of
triethylamine to yield enyne allene 38 in excellent yield
(Scheme 8). Heating this compound at 37 °C in the
presence of 1,4-CHD as a hydrogen atom donor yielded
enyne allene-cyclized product 40 in 70% yield. This
(16) (a) Grissom, J . W.; Huang, D. Angew. Chem., Int. Ed. Engl.
1995, 34, 2037. (b) Grissom, J . W.; Slattery, B. J . Tetrahedron Lett.
1994, 35, 5137.
(17) For examples of [2,3] sigmatropic rearrangements of propargyl
diphenylphosphinites, see: (a) Nicolaou, K. C.; Skokotas, G.; Maligres,
P.; Zuccarello, G.; Schweiger, E. J .; Toshima, K.; Wendeborn, S. Angew.
Chem., Int. Ed. Engl. 1989, 28, 1272. (b) Nicolaou, K. C.; Maligres, P.;
Shin, J .; de Leon, E.; Rideout, D. J . Am. Chem. Soc. 1990, 112, 7825.
(c) Nagata, R.; Yamanaka, H.; Murahashi, E.; Saito, I. Tetrahedron
Lett. 1990, 31, 2907. (d) Nagata, R.; Yamanaka, H.; Okazaki, E.; Saito,
I. Tetrahedron Lett. 1989, 30, 4995.

608 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
Sch em e 9
Sch em e 10
observation corresponds to the behavior of a similar
substrate described by Nicolaou that has been reported
to cyclize at 37 °C in a very similar yield.17b
Having established the feasibility of carrying an enyne
allene cyclization on a substrate with a phosphine oxide
substituent prepared by a [2,3] sigmatropic rearrange-
ment of a phosphinite, the next goal was to couple this
cyclization with a subsequent radical cyclization. Treat-
ment of compound 35 with chlorodiphenylphosphine in
THF at low temperature yielded enyne allene compound
41 in 99% yield (Scheme 9). Thermolysis of enyne allene
41 at 37 °C in the presence of 1,4-CHD resulted in no
reaction. However, increasing the thermolysis temper-
ature to 75 °C yielded tandem enyne allene-radical
cyclization product 42. Due to the difficulty in purifying
the polar phosphine oxide 42, this compound was sub-
jected to a Horner-Wittig elimination to yield benz[e]-
indene compound 43 in an overall yield of 70% from 41.
Although cyclization of 41 did occur at 50 °C, the yield
obtained at this temperature was low and the product
mixture more complex.
These results combined with the poor reactions ob-
tained with C-1-substituted allene 24 substantiate the
assumption that an unfavorable interaction between a
C-1 allene substituent and the aryl ring of the enyne
allene hinders the cyclization reaction. In substrates 44
and 45 there are unfavorable steric interactions between
the (diphenylphosphinyl) group and the aryl ring of the
enyne allene, causing the phosphinyl group to rotate the
allene out of the plane defined by the aryl group. The
enyne allene would therefore no longer be coplanar and
thus be unable to participate in the Myers cyclization. It
is possible that a similar interaction between the C-1
allene CH2CHO group and the aryl ring resulted in poor
yields during the cyclization of [3,3]-generated enyne
allene 24 to form 25 (Scheme 4). When the substituent
was shifted to the C-3 allene position as in 28 and 31,
the reactions proceeded more favorably (Schemes 5 and
6). Therefore, to avoid this unfavorable steric interaction,
we investigated the cyclization behavior of substrates 38
and 41 as previously described.
If an unfavorable steric interaction occurred between
the C-1 allene phosphine oxide and the ortho hydrogen
of the aromatic enyne allene, it was possible that remov-
ing that hydrogen would improve the reaction. There-
fore, we then addressed the question of whether nonar-
omatic enyne allene precursors that carry a phosphine
oxide substituent at the C-1 position of the allene would
participate in a tandem enyne allene-radical cyclization.
To test the feasibility of this hypothesis, a variety of
enediyne alcohols were synthesized (Scheme 11). We
were encouraged that this approach might be fruitful
because of earlier work by Saito describing the cyclization
of nonaromatic enyne allenes containing C-1 phosphine
oxides.17c
Prior to the successful outcome of the cyclization
experiments with substrates 38 and 41, both of which
carry the phosphine oxide substituent at the C-3 position
of the allene moiety, we had explored the cyclization
behavior of the corresponding substrates 44 and 45
carrying the phosphine oxide substituent at the C-1
position of the allene functionality. These systems were
investigated first since they were easily prepared in three
to four steps (Scheme 7). Treatment of enediyne 37 with
chlorodiphenylphosphine at low temperature resulted in
a [2,3] sigmatropic shift to afford enyne allene 44 in 98%
yield (Scheme 10). However, when this compound was
heated to 75 °C in the presence of 1,4-CHD as a hydrogen
donor, there was no evidence for tandem enyne allene-
radical cyclization product 46 and only slow decomposi-
tion occurred. Attempts to effect a cyclization at higher
temperatures resulted in a complex mixture of products.
To test whether the problem arose during the enyne
allene cyclization or the subsequent radical cyclization,
the cyclization of enyne allene 45 was carried out. The
expected tandem enyne allene-radical cyclization prod-
uct 47 could not be detected, and the starting material
slowly underwent decomposition.

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 609
Sch em e 11
Sch em e 12
the resulting primary alcohol with acetyl chloride and
triethylamine in dichloromethane, and desilylation with
tetra-n-butylammonium fluoride (TBAF) in THF afforded
allylic acetate 54 in a total yield of 53% from 50.
Substrates 52 and 53 were prepared in a fashion similar
to that of compound 51, using trimethyl 2-methylphospho-
noacetate in the Horner-Emmons reaction and separat-
ing the (E)- and (Z)-stereoisomers prior to desilylation.
Thus, compound 52 (E isomer) was obtained in 58% from
50, and compound 53 (Z isomer) was obtained in 7% from
50. Wittig reaction19 of aldehyde 50 with (methoxymeth-
yl)triphenylphosphonium chloride and potassium tert-
butoxide in THF at -78 °C and subsequent desilylation
with TBAF in THF gave rise to enol ether 55 in a total
yield of 55% over two steps. O-Benzyloxime ether 56 and
diphenylhydrazone 57 were each obtained by condensing
aldehyde 50 with the respective amine hydrochloride (O-
benzylhydroxylamine hydrochloride or 1,1-diphenylhy-
drazine hydrochloride), followed by desilylation with
TBAF in THF. With this strategy, 56 and 57 were
obtained in 78% and 88% combined yields, respectively.
The synthesis of two additional precursors is illus-
trated in Scheme 12. The R,â-unsaturated enediyne ester
59 was prepared in a sequence similar to that of
substrate 51. Starting from cis-dichloroethylene, two
consecutive palladium(0)-catalyzed coupling reactions
with 4-pentynol and 3-((tert-butyldimethylsilyl)oxy)-1-
butyne followed by PCC oxidation afforded aldehyde 58,
which was converted to 59 by a Horner-Emmons reac-
tion with trimethyl phosphonoacetate and subsequent
desilylation with BF3 etherate. The overall yield of
Syn th esis of P r ecu r sor s for th e Ta n d em En yn e
Allen e-Ra d ica l Cycliza tion of Non a r om a tic En yn e
Allen es via [2,3] Sigm a tr op ic Rea r r a n gem en t. Sev-
eral substrates were synthesized from easily synthesized
enediyne aldehyde 50, which was readily available from
cis-dichloroethylene in three straightforward steps
(Scheme 11). Two consecutive palladium(0)-catalyzed
coupling reactions under modified Castro-Stephens con-
ditions with 4-pentynol and 3-((tert-butyldimethylsilyl)-
oxy)propyne followed by PCC oxidation of the resulting
primary alcohol afforded enediyne aldehyde 50 in a
combined yield of 46% over three steps.
The R,â-unsaturated enediyne ester 51 was obtained
in 74% yield from 50 by a Horner-Emmons reaction
under Roush-Masamune conditions15 with trimethyl
phosphonoacetate in the presence of lithium chloride and
DBU in acetonitrile, followed by subsequent desilylation
with BF3 etherate in dichloromethane (Scheme 11).
Reduction of 51 with diisobutylaluminum hydride
(DIBAL)18 in dichloromethane at 0 °C, esterification of
(18) Winterfeldt, E. Synthesis 1975, 617.
(19) For general reviews of the Wittig reaction, see: (a) Pommer,
H.; Thieme, P. C. Top. Curr. Chem. 1983, 109, 165. (b) Bestmann, H.
J .; Vostrowsky, O. Top. Curr. Chem. 1983, 109, 85. (c) Pommer, H.
Angew. Chem., Int. Ed. Engl. 1977, 16, 423. (d) Maercker, A. Org.
React. 1965, 14, 270.

610 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
dride-mediated radical cyclizations7h reveals that the
current reaction likely proceeds through a radical inter-
mediate and the geometry of the olefin within the R,â-
unsaturated ester has no effect on either diastereoselec-
tivity or yield of the radical cyclization.
Ta ble 1. Ta n d em En yn e Allen e-Ra d ica l Cycliza tion of
Su bstr a tes 62-67
In order to test this methodology with other radical
acceptors and to determine the scope of the reaction, both
allylic acetate 54 and enol ether 55 were investigated.
Treatment of 54 and 55 with chlorodiphenylphosphine
followed by thermolysis of the corresponding enyne
allenes 65 and 66 at physiological temperature (37 °C)
in the presence of 1,4-CHD (3.5 M) produced the 2,3-
dihydroindenes 70 and 71 in 55% and 62% overall yields,
respectively. It should be pointed out that the tandem
enyne allene-radical cyclization of 66 bearing a methyl
vinyl ether in the radical acceptor side chain occurred
smoothly at 37 °C, while the enol ether functionality in
a nonaromatic enediyne similar to substrate 55 did not
survive at all in the tandem enediyne-radical cyclization
at high temperature.7d,h
enyne
enediyne allene R1
R2
R3
product yield,a
%
51
52
53
54
55c
59
62
63
64
65
66
67
H
H
H
H
H
Me
H
CO2Me
CO2Me
68
68
70
67
62
55
52
Me
69a ,bb
69a ,bb
CO2Me Me
H
H
H
CH2OAc 70
OMe
CO2Me
71
72
Finally, enediyne 59 was chosen to explore how a
simple alkyl substituent at the C-3 position of the
resulting allene would affect the enyne allene cyclization.
When enediyne 59 was treated with chlorodiphenylphos-
phine and triethylamine at -78 °C and the mixture
allowed to stir at 0 °C, enyne allene 67 was formed as
the major product along with an impurity (ca. 15% based
on 1H NMR). Subsequent thermolysis of crude enyne
allene 67 at 37 °C in the presence of 1,4-CHD (3.5 M)
afforded 2,3-dihydroindene 72 in 52% overall yield from
59 and 12% of a minor product which was identical to
the impurity formed in the [2,3] sigmatropic shift and
which appeared to be nonrearranged phosphite of 59 on
a
b
Overall yield over two steps. Isolated as a 3.5:1 mixture of
diastereomers. c E:Z ) 6:1.
compound 59 in this five-step sequence from cis-dichlo-
roethylene was 34%. Enediyne aldehyde 60 was obtained
in a combined yield of 48% from cis-dichloroethylene by
performing two consecutive palladium(0)-catalyzed cou-
pling reactions with 5-hexynol and 3-((tert-butyldimeth-
ylsilyl)oxy)propyne followed by PCC oxidation of the
intermediate enediyne alcohol. Condensing aldehyde 60
with 1,1-diphenylhydrazine hydrochloride in the presence
of pyridine in dichloromethane, followed by desilylation
with TBAF in THF, afforded enediyne diphenylhydrazone
61 in 87% yield over two steps.
1
the basis of H NMR data. It is possible that the C-3
Resu lts of th e [2,3] Sigm a tr op ic Rea r r a n gem en t-
Med ia ted Ta n d em En yn e Allen e-Ra d ica l Cycliza -
tion Exp er im en ts In volvin g Non a r om a tic En yn e
Allen e Su bstr a tes. Given the reliability of the R,â-
unsaturated ester as a radical acceptor in tandem ene-
diyne or enyne allene-radical cyclizations,7 we initially
investigated enyne allene 62 (Table 1). When enediyne
51 was treated with chlorodiphenylphosphine and tri-
ethylamine in dichloromethane at -78 °C and the
mixture allowed to stir at 0 °C, enyne allene 62 was
formed via a [2,3] sigmatropic rearrangement. Unfor-
tunately, 62 was isolated in poor yield (ca. 10%) due to
its decomposition on silica gel and alumina. Therefore,
the subsequent cyclization was performed without the
purification of 62 immediately following the sigmatropic
shift. Upon mild thermolysis of crude enyne allene 62
in anhydrous benzene at 37 °C in the presence of a large
concentration of 1,4-CHD (c ) 3.5 M) for 12 h, 2,3-
dihydroindene derivative 68 was isolated in 68% overall
yield from enediyne 51.
Encouraged by the successful tandem enyne allene-
radical cyclization of 62, enyne allene 63 generated from
a [2,3] sigmatropic shift of 52 was thermolyzed at 37 °C
in the presence of 1,4-CHD (3.5 M) to provide 2,3-
dihydroindenes 69a and 69b as a 3.5:1 diastereomeric
mixture in 70% overall yield from 52 (Table 1). When
the similar reaction sequence was applied to 53 (Z isomer
of 52), the 2,3-dihydroindenes 69a and 69b were obtained
as an identical 3.5:1 diastereomeric mixture in 67%
overall yield from 53. The fact that the diastereoselec-
tivities observed in both reactions are identical with
previous results observed in the tandem enediyne-
radical cyclizations and the comparable tributyltin hy-
methyl group sterically impedes the [2,3] sigmatropic
shift and the phosphine oxide simply undergoes oxida-
tion. Additional substituent studies were not carried out.
While carbon-carbon double bonds are established as
radical acceptors in the 5-exo ring closure mode, O-
benzyloxime ethers as well as N,N-diphenylhydrazones
have only recently emerged as suitable carbon-nitrogen
radical acceptors in 5-exo and 6-exo radical ring closure
reactions.7dh,20,21 Cyclization reactions onto these accep-
(20) For the use of oxime ethers in radical cyclization reactions,
see: (a) Chiara, J . L.; Marco-Contelles, J .; Khiar, N.; Gallego, P.;
Destabel, C.; Bernabe´, M. J . Org. Chem. 1995, 60, 6010. (b) Marco-
Contelles, J .; Destabel, C.; Chiara, J . L.; Bernabe´, M. Tetrahedron:
Asymmetry 1995, 6, 1547. (c) Keck, G. E.; McHardy, S. F.; Murry, J .
A. J . Am. Chem. Soc. 1995, 117, 7289. (d) Santagostino, M.; Kilburn,
J . D. Tetrahedron Lett. 1995, 36, 1365. (e) Kiguchi, T.; Tajiri, K.;
Ninimiya, I.; Naito, T.; Hiramatsu, H. Tetrahedron Lett. 1995, 36, 253.
(f) Booth, S. E.; J enkins, P. R.; Swain, C. J .; Sweeney, J . B. J . Chem.
Soc., Perkin Trans. 1 1994, 3499. (g) Naito, T.; Tajiri, K.; Harimoto,
T.; Ninomiya, I.; Kiguchi, T. Tetrahedron Lett. 1994, 35, 2205. (h)
Ingall, A. H.; Moore, P. R.; Roberts, S. M. J . Chem. Soc., Chem.
Commun. 1994, 83. (i) Pattenden, G.; Schultz, D. J . Tetrahedron Lett.
1993, 34, 6787. (j) Marco-Contelles, J .; Ruiz, P.; Martı´nez, L.; Mart´ınez-
Grau, A. Tetrahedron 1993, 49, 6669. (k) Simpkins, N. S.; Stokes, S.;
Whittle, A. J . J . Chem. Soc., Perkin Trans. 1 1992, 2471. (l) Marco-
Contelles, J .; Ruiz, P.; Sa´nchez, B.; J imeno, M. L. Tetrahedron Lett.
1992, 33, 5261. (m) Hatem, J .; Henriet-Bernard, C.; Grimaldi, J .;
Maurin, R. Tetrahedron Lett. 1992, 33, 1057. (n) Marco-Contelles, J .;
Pozuelo, C.; J imeno, M. L.; Mart´ınez, L.; Mart´ınez-Grau, A. J . Org.
Chem. 1992, 57, 2625. (o) Booth, S. E.; J enkins, P. R.; Swain, C. J . J .
Chem. Soc., Chem. Commun. 1991, 1248. (p) Marco-Contelles, J .;
Mart´ınez, L.; Mart´ınez-Grau, A. Tetrahedron: Asymmetry 1991, 2, 961.
(q) Marco-Contelles, J .; Mart´ınez-Grau, A.; Bernabe, M.; Martin, N.;
Seoane, C. Synlett 1991, 165. (r) Enholm, E. J .; Burroff, J . A.; J aramillo,
L. M. Tetrahedron Lett. 1990, 31, 3727. (s) Parker, K. A.; Spero, D.
M.; Van Epp, J . J . Org. Chem. 1988, 53, 4628. (t) Bartlett, P. A.;
McLaren, K. L.; Ting, P. C. J . Am. Chem. Soc. 1988, 110, 1633. (u)
Hart, D. J .; Seely, F. L. J . Am. Chem. Soc. 1988, 110, 1631. (v) Corey,
E. J .; Pyne, S. G. Tetrahedron Lett. 1983, 24, 2821.

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 611
Sch em e 13
Sch em e 14
C-1 position of the allene moiety show that the tandem
enyne allene-radical cyclization (62 f 68) represents a
useful tool for the construction of indan derivatives from
simple enediyne precursors that are readily available
from commercially available cis-dichloroethylene. The
corresponding aromatic enyne allene substrate does not
participate in a tandem enyne allene-radical cyclization
(37 f 46) presumably due to an unfavorable steric
interaction between the large C-1 phosphine oxide sub-
stituent on the allene and the adjacent aromatic hydro-
gen atom. Aromatic enyne allene compounds that carry
a phosphine oxide substituent at the C-3 position of the
allene unit undergo a tandem enyne allene-radical
cyclization (35 f 42) and provide the respective benz[e]-
indene derivatives in good yields; however, the synthesis
of the cyclization precursors is rather lengthy.
tors would offer the advantage of forming a ring structure
that bears a heteroatom at the position of the ring closure
rather than a carbon. Since numerous important natural
products contain nitrogen functionalities, a successful
radical cyclization onto oxime ethers or hydrazones could
provide access to these compounds and thus broaden the
applicability of the tandem enyne allene-radical cycliza-
tion methodology. The nitrogen could also serve as a
handle to introduce additional functionalization at this
position. To test the feasibility of these radical acceptors
in the tandem enyne allene-radical cyclization method-
ology, enediyne substrates 56 and 57 were investigated
(Scheme 13). While the treatment of oxime ether 56 with
chlorodiphenylphosphine and triethylamine in dichlo-
romethane and subsequent mild thermolysis in benzene
at 37 °C provided the corresponding indene derivative
75 in only moderate yield (25%), the formation of indenyl
diphenylhydrazine 76 from enediyne 57 proceeded much
more efficiently in a yield of 58%. It is unclear why the
hydrazone is a superior acceptor to the oxime ether.
Since all biologically active steroids contain several six-
six fused rings, it would be useful to utilize the current
methodology to construct this ring system. To study
whether a six-membered ring could be prepared using
the tandem enyne allene-radical cyclization, diphenyl-
hydrazone 77 was subjected to the cyclization conditions
at 37 °C; however, tetraline derivative 79 could only be
isolated in a moderate yield of 22% (Scheme 13).
The mechanism of the overall transformation is out-
lined in Scheme 14. Enyne allene 62, generated from a
[2,3] sigmatropic rearrangement of corresponding ene-
diyne 51, undergoes an enyne allene cyclization (Myers
cyclization) to form biradical 80. Subsequent 5-exo (6-
exo) radical cyclization of aryl radical 80 followed by
hydrogen abstraction from 1,4-CHD furnish indan de-
rivative 68. The mechanism of cyclization is the same
as that for the enyne allenes generated from the [3,3]
sigmatropic shift reaction (17 f 33a ,b; Scheme 6).
The experiments involving nonaromatic enyne allene
substrates bearing a phosphine oxide substituent at the
Ta n d em En yn e Allen e-Ra d ica l Cycliza tion via
Ba se-Ca ta lyzed Isom er iza tion of En ed iyn e
Su lfon es22
Although the previously discussed method appears to
be a very efficient method for the construction of multi-
cyclic compounds, it requires the use of a phosphine oxide
substituent for the successful conversion of the starting
enyne allene substrates. This phosphorous substituent,
however, is not easily converted into useful functionality
for the synthetic chemist if a further elaboration of the
target molecules were desired. Therefore, we directed
our effort toward the use of the more versatile phenyl-
sulfonyl group in the tandem enyne allene-radical
cyclization methodology.
Nicolaou,23cd Wu,23a and Shibuya23e have reported that
base-catalyzed isomerization of an enediyne sulfone leads
to an enyne allene sulfone which undergoes cyclization
at 25-37 °C. To explore the feasibility of this mode of
enyne allene formation and cyclization for aromatic
(22) Grissom, J . W.; Klingberg, D. Tetrahedron Lett. 1995, 36, 6607.
(23) (a) Wu, M.-J .; Lin, C.-F.; Wu, J .-S.; Chen, H.-T. Tetrahedron
Lett. 1994, 35, 1879. (b) Toshima, K.; Ohta, K.; Ohtsuka, A.; Mat-
sumura, S.; Nakata, M. J . Chem. Soc., Chem. Commun. 1993, 1406.
(c) Nicolaou, K. C.; Wendeborn, S.; Maligres, P.; Isshiki, K.; Zein, N.;
Ellestad, G. Angew. Chem., Int. Ed. Engl. 1991, 30, 418. (d) Nicolaou,
K. C.; Skokotas, G.; Maligres, P.; Zuccarello, G.; Schweiger, E. J .;
Toshima, K.; Wendeborn, S. Angew. Chem., Int. Ed. Engl. 1989, 28,
1272. (e) Sakai, Y.; Bando, Y.; Shishido, K.; Shibuya, M. Tetrahedron
Lett. 1992, 33, 957.
(21) For the use of diphenylhydrazones in radical cyclization reac-
tions, see: (a) Sturino, C. F.; Fallis, A. G. J . Org. Chem. 1994, 59, 6514.
(b) Sturino, C. F.; Fallis, A. G. J . Am. Chem. Soc. 1994, 116, 7447.

612 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
Sch em e 15
Sch em e 16
enediyne precursors, we synthesized enediyne 81 from
3-(2-ethynylphenyl)-2-propyn-1-ol (36) (Scheme 15). Me-
sylation of the alcohol with methanesulfonyl chloride and
triethylamine in dichloromethane, nucleophilic exchange
of the methanesulfonyl group with sodium phenyl sulfide,
and oxidation of the resulting thioether with m-chloro-
perbenzoic acid (m-CPBA) provided enediyne sulfone 81
in an excellent yield of 86% from 36. When enediyne
sulfone 81 was heated in anhydrous benzene at 30 °C in
the presence of triethylamine and a large excess of 1,4-
CHD (c ) 3.5 M) as a hydrogen atom donor, the simple
enyne allene cyclization product 82 was isolated in 68%
yield (Scheme 15).
Given the successful cyclization of substrate 81, at-
tention was focused on trapping the intermediate aryl
radical in the enyne allene cyclization with a pendent
olefin. Since the R,â-unsaturated methyl ester had been
employed successfully in a variety of different tandem
enediyne- and tandem enyne allene-radical cyclizations
in our laboratory,7 the cyclizations of enediyne sulfones
84-88 (Scheme 16) were investigated.
Syn th esis of P r ecu r sor s for th e Ta n d em En yn e
Allen e-Ra d ica l Cycliza tion of Ar om a tic En yn e Al-
len es via Ba se-Ca ta lyzed Isom er iza tion of En e-
d iyn e Su lfon es. Enediyne sulfones 84-88 were each
synthesized in a straightforward manner from enediyne
aldehyde 83, which was prepared from 3-(2-iodophenyl)-
2-propyn-1-ol (8) (Scheme 16). Aryl iodide 8 was sub-
jected to a palladium(0)-catalyzed coupling reaction with
5-((tert-butyldimethylsilyl)oxy)-1-pentyne in the presence
of bis(triphenylphosphine)palladium(II) chloride and cop-
per(I) iodide as well as triethylamine in THF. Subse-
quent conversion of the primary alcohol into the phenyl
sulfide via the methanesulfonate, desilylation with acetic
acid in a THF-water mixture,24 and Swern oxidation25
cleanly afforded key intermediate 83 in a total yield of
75% over five steps. The desilylation step had to be
performed with a 3:1 mixture of acetic acid and water;
the use of lower acetic acid concentrations was ineffective.
Attempts to effect the deprotection with tetra-n-butyl-
ammonium fluoride in THF resulted in decomposition of
starting material.
obtained in 55% as a 3:2 mixture of cis/trans isomers from
83 by a Horner-Emmons reaction with diethyl (cyano-
methyl)phosphonate26 and potassium tert-butoxide in
THF followed by subsequent oxidation with m-CPBA.
Horner-Emmons reaction of aldehyde 83 with trimethyl
phosphonoacetate, subsequent reduction of the R,â-
unsaturated enediyne ester with diisobutylaluminum
hydride (DIBAL), and oxidation with m-CPBA at -78 °C
provided allylic enediyne alcohol 87 in a moderate yield
of 27% over three steps. To guarantee good yields in all
Horner-Emmons reactions of intermediate 83, the reac-
tion mixtures had to be worked up immediately after the
reagents were added. O-Benzyloxime ether 88 was
The R,â-unsaturated enediyne ester 84 was obtained
from aldehyde 83 in 69% by a Horner-Emmons reaction
under Roush-Masamune conditions15 with trimethyl
phosphonoacetate and subsequent m-CPBA oxidation in
dichloromethane at 0 °C. Following the same procedure
using trimethyl 2-methylphosphonoacetate in the Hor-
ner-Emmons reaction, enediyne sulfone 85 was prepared
in 44% total yield. Unsaturated enediyne nitrile 86 was
(26) For general reviews of the Horner-Emmons reaction, see: (a)
Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863. (b) Wadsworth,
W. S., J r. Org. React. 1977, 25, 73. (c) Boutagy, J .; Thomas, R. Chem.
Rev. 1974, 74, 87. For Wittig reactions or Horner-Emmons reactions
that employ cyano-substituted phosphoranes or cyanomethyl-substi-
tuted phosphonates, see: (d) Ullas, G. V.; Chu, C. K.; Ahn, M. K.;
Kosugi, Y. J . Org. Chem. 1988, 53, 2413. (e) Piechucki, C. Synthesis
1974, 869. (f) Tronchet, J . M. J .; Baehler, B.; Eder, H.; Le-Hong, N.;
Perret, F.; Poncet, J .; Zumwald, J .-B. Helv. Chim. Acta 1973, 56, 1310.
(g) Bose, A. K.; Dahill, R. T., J r. J . Org. Chem. 1965, 30, 505. (h)
Schiemenz, G. P.; Engelhard, H. Chem. Ber. 1961, 94, 578.
(24) Corey, E. J .; Venkateswarlu, A. J . Am. Chem. Soc. 1972, 94,
6190.
(25) Mancuso, A. J .; Huang, S.-L.; Swern, D. J . Org. Chem. 1978,
43, 2480.

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 613
Ta ble 2. Ta n d em En yn e Allen e-Ra d ica l Cycliza tion of
Su bstr a tes 84-88
Sch em e 17
enediyne
X
product
yield, %
84
CHCO2Me
C(Me)CO2Me
CHCN
CHCH2OH
NOCH2Ph
89
90c
91
92
93
76
78
72
68
71
85
86a
87
88b
a
b
Prepared as a 3:2 mixture of cis/ trans isomers. Prepared as
a 1:1 mixture of syn/ anti isomers. c Isolated as a 3.5:1 mixture of
diastereomers.
prepared in 79% yield as a 1:1 mixture of syn/anti isomers
by condensing enediyne aldehyde 83 with O-benzylhy-
droxylamine and subsequent low-temperature m-CPBA
oxidation. To our delight, the low-temperature oxidation
led to the selective oxidation of the sulfide over the oxime
carbon-nitrogen bond and provided the desired sulfone
product in a good 84% yield. When the extremely mild
oxidation agent tetra-n-propylammonium perruthenate
(TPAP) was used as described by Kende for the selective
oxidation of sulfides to sulfones,27 the desired sulfone 88
was not formed and decomposition was observed.
Although the substrates described in the previous
paragraph could all be synthesized in a straightforward
fashion, the general use of this synthetic scheme might
prove rather challenging. The key steps that include
both the oxidation of the sulfide to the corresponding
sulfone in the presence of the oxime ether or olefin as
well as the elaboration of the aldehyde in 83 in the
presence of the thioether side chain involve certain
compatibility problems, which limit the usefulness of the
synthetic route used for the preparation of these sub-
strates.
tributyltin hydride-mediated radical cyclization.7g This
observation suggests that all these transformations
presumably proceed through a common radical interme-
diate, while the geometry of the olefin within the R,â-
unsaturated ester has no effect on the diastereomeric
outcome of the radical cyclization (vide supra).
To test the use of other radical acceptors in this
reaction, enediyne sulfones 86-88 containing an R,â-
unsaturated nitrile, a simple alkene, and an oxime
ether,20 respectively, were subjected to the standard
reaction conditions to furnish 2,3-dihydrobenz[e]indene
derivatives 91 (72%), 92 (68%), and 93 (71%) in good
yields (Table 2). It is noteworthy that the elimination of
O-benzylhydroxylamine that was observed in the respec-
tive high-temperature tandem enediyne-radical cycli-
zation7d did not occur due to the low temperature
employed in the present reaction.
When 84 was heated at 37 °C for 14 h in anhydrous
benzene in the presence of triethylamine and a large
excess of 1,4-CHD (c ) 3.5 mol/L), tandem enyne allene-
radical cyclization product 89 was formed in 76% yield
(Table 2). Notably, this product was formed both in good
yield and at low temperature. Compound 84 has the
sulfone group in the C-3 allene position and like the C-3
substituted enyne allenes 31 (Scheme 6) and 41 (Scheme
9) generated from the [3,3] and [2,3] sigmatropic shifts,
respectively, this allene substitution pattern is important
to the success of the reaction.
To test the generality of this reaction, enediyne sul-
fones 85-88 (Scheme 16) were each subjected to the same
reaction conditions. Treatment of enediyne sulfone 85
under these conditions resulted in the formation of the
corresponding tandem enyne allene-radical cyclization
product 90 in 78% yield (Table 2). It is noteworthy that
product 90 was isolated as a 3.5:1 mixture of diastereo-
mers. This result is identical with previous results
observed both in tandem enediyne- and tandem enyne
allene-radical cyclizations as well as the comparable
The mechanism of the overall transformation is out-
lined in Scheme 17 for enediyne substrate 84. Enyne
allene 94 generated from a base-catalyzed isomerization
of corresponding enediyne 84 undergoes an enyne allene
cyclization (Myers cyclization) to form biradical 95.
Subsequent 5-exo radical cyclization of the aryl radical
in intermediate 95 followed by hydrogen atom abstraction
from 1,4-CHD furnished 2,3-dihydrobenz[e]indene de-
rivative 89. This mechanism is similar to the cyclization
of the enyne allenes generated from the [3,3] and [2,3]
sigmatropic shifts (Schemes 6 and 14, respectively).
With these experiments, we have extended the tandem
enyne allene-radical cyclization to enediyne sulfone
substrates. The cyclization precusors can be readily
synthesized from commercially available starting materi-
als. The tandem enyne allene-radical cyclization of
aromatic enediyne sulfones occurs at physiological tem-
perature (ca. 37 °C), and the 2,3-dihydrobenz[e]indene
derivatives are formed in good overall yields. The
sulfones formed in these tandem enyne allene-radical
cyclizations provide the opportunity for further elabora-
tion, since sulfones exhibit a high synthetic versatility.
In particular, due to the mild reaction conditions, this
methodology should be tolerant of a variety of functional-
ity and should be applicable to the synthesis of complex
(27) (a) Guertin, K. R.; Kende, A. Tetrahedron Lett. 1993, 34, 5369.
(b) For
a review of the oxidizing agent tetra-n-propylammonium
perruthenate (TPAP), see: Ley, S. V.; Norman, J .; Griffith, W. P.;
Marsden, S. P. Synthesis 1994, 639.

614 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
(0.012 g, 0.017 mmol), copper(I) iodide (0.006 g, 0.030 mmol),
and (trimethylsilyl)acetylene (0.070 mL, 0.500 mmol) in THF
(30 mL). The reaction mixture was stirred at room temper-
ature for 6 h. The mixture was then concentrated and filtered
through Florisil (2:1, hexanes/ethyl acetate). The solvent was
removed in vacuo to give a brown oil, which was dissolved in
methanol (5 mL) and treated with a catalytic amount of
potassium carbonate (≈ 5 mg) at room temperature for 8 h.
The reaction mixture was filtered through Florisil (2:1, hex-
anes/ethyl acetate). Removal of the solvent followed by column
chromatography of the residue (94:5:1 hexanes/ethyl acetate/
triethylamine) afforded 9 as a pale yellow oil (0.056 g, 93%
over two steps): TLC Rf 0.52 (5:1, hexanes/ethyl acetate); IR
hetero- and carbocycles. This method is comparable to
the low-temperature tandem nonaromatic enyne allene-
radical cyclizations of phosphine oxides described previ-
ously. On the other hand, the synthesis of similar
compounds via a tandem enediyne-radical cyclization
requires temperatures in excess of 220 °C.7
Con clu sion
In an effort to lower the temperatures required to
prepare multicyclic compounds using the tandem ene-
diyne-radical cyclization, we have developed the tandem
enyne allene-radical cyclization which proceeds at lower
temperatures. These reactions utilized three different
methods for the preparation of the enyne allenes includ-
ing a [3,3] sigmatropic shift, a [2,3] sigmatropic shift, and
a base-catalyzed isomerization of a propargyl sulfone.
Many of these cyclizations occur at temperatures as low
as 37 °C. Given the low temperatures and the ease of
preparation of many of the cyclization substrates, we
expect that the tandem enyne allene-radical cyclization
will prove to be a useful method for the preparation of
various biologically active carbocycles and heterocycles.
Further studies utilizing the present compounds for DNA
cleavage and drug delivery are in progress.
1
(neat) ν 3302, 2249, 2133, 1638, 1186 cm-1; H NMR δ 7.48-
7.36 (m, 2H), 7.28-7.18 (m, 2H), 6.48 (dd, J ) 14.4, 6.6 Hz,
1H), 4.61 (s, 2H), 4.36 (dd, J ) 14.4, 2.4 Hz, 1H), 4.11 (dd, J
) 6.6, 2.4 Hz, 1H), 3.26 (s, 1H); 13C NMR δ 150.4, 132,5, 132.2,
128.5, 128.3, 125.3, 124.7, 88.5, 87.7, 85.2, 81.8, 81.2, 56.6;
HRMS (EI) calcd for C13H10O (M+) 182.0732, found 182.0725.
P r ep a r a tion of 5-(2-Iod op h en yl)-4-p en tyn -1-ol (10).
1,2-Diiodobenzene (7) (0.396 mL, 1.000 g, 3.03 mmol) was
subjected to coupling conditions similar to those for the
preparation of 8 using triethylamine (1.470 mL, 0.920 g, 9.10
mmol), bis(triphenylphosphine)palladium(II) chloride (0.064 g,
0.09 mmol), copper(I) iodide (0.057 g, 0.30 mmol), and 4-pen-
tynol (0.419 mL, 0.379 g, 4.50 mmol) in THF (30 mL).
Purification by radial chromatography with an 85:15 mixture
of hexanes/diethyl ether yielded 0.486 g (56%) of 10 as a pale
yellow oil: TLC Rf 0.25 (2:1 hexanes/ethyl acetate); IR (neat)
ν 3374 (br), 3059, 2947, 2230 cm-1; 1H NMR δ 1.52 (1H, s, br,
OH), 1.89 (2H, quintet, J ) 6.3 Hz), 2.59 (2H, t, J ) 6.3 Hz),
3.87 (2H, t, J ) 6.3 Hz), 6.94 (1H, td, J ) 7.5, 1.5 Hz), 7.24
(1H, td, J ) 7.5, 1.5 Hz), 7.38 (1H, dd, J ) 7.8, 1.5 Hz), 7.79
(1H, dd, J ) 7.8, 1.5 Hz); 13C NMR δ 138.6, 132.5, 130.2, 128.9,
127.7, 101.0, 93.6, 83.4, 61.7, 31.0, 16.1; HRMS (EI) calcd for
C11H11IO (M+) 285.9853, found 285.9849.
Exp er im en ta l Section 28
P r ep a r a tion of 3-(2-Iod op h en yl)-2-p r op yn -1-ol (8). 1,2-
Diiodobenzene (7) (0.396 mL, 1.000 g, 3.03 mmol) was dis-
solved in 30 mL of THF. After the addition of triethylamine
(1.267 mL, 0.920 g, 9.09 mmol) and bis(triphenylphosphine)-
palladium(II) chloride (0.064 g, 0.09 mmol), the reaction
mixture was stirred for 10 min. Then copper(I) iodide (0.058
g, 0.30 mmol) was added and the reaction mixture stirred for
an additional 10 min, before propargyl alcohol (0.265 mL, 0.255
g, 4.55 mmol) was added in one portion via syringe. The
reaction was allowed to stir at room temperature overnight.
The solvent was removed in vacuo and the residue filtered
through silica gel using a 1:1 mixture of hexanes/diethyl ether.
Purification by radial chromatography with an 85:15 mixture
of hexanes/diethyl ether yielded 0.407 g (52%) of 8 as a pale
yellow oil: TLC Rf 0.26 (3:1 hexanes/ethyl acetate); IR (neat)
ν 3345 (br), 3057, 2913, 2861, 2238 cm-1; 1H NMR δ 2.14 (1H,
s, br), 4.54 (2H, s), 6.97 (1H, ddd, J ) 9.3, 8.1, 1.7 Hz), 7.26
(1H, ddd, J ) 8.8, 7.5, 1.2 Hz), 7.42 (1H, dd, J ) 7.8, 1.7 Hz),
7.81 (1H, ddd, J ) 8.1, 1.2, 0.5 Hz); 13C NMR δ 138.6, 132.7,
129.6, 129.0, 127.8, 100.7, 91.0, 87.6, 51.6; HRMS (EI) calcd
for C9H7IO (M+) 257.9541, found 257.9565.
P r ep a r a tion of 2-Eth yn yl-1-(3-(vin yloxy)-1-p r op yn yl)-
ben zen e (9). A mixture of 8 (0.300 g, 1.16 mmol) and
mercury(II) acetate (0.112 g, 0.350 mmol) in ethyl vinyl ether
(15 mL) was heated to reflux under nitrogen for 2 d. The
reaction mixture was filtered through Florisil using a 1:1
mixture of hexanes/ethyl acetate. Removal of the solvent
followed by column chromatography of the residue (90:9:1
hexanes/ethyl acetate/triethylamine) gave 2-iodo-1-[3-(vinyl-
oxy)-1-propynyl]benzene as a yellow oil (0.237 g, 72%): TLC
Rf 0.49 (5:1 hexanes/ethyl acetate); IR (neat) ν 2235, 1620,
1186, 754 cm-1; 1H NMR δ 7.81 (dd, J ) 8.1, 1.2 Hz, 1H), 7.44
(dd, J ) 7.5, 1.8 Hz, 1H), 7.27 (td, J ) 7.5, 1.8 Hz, 1H), 6.98
(td, J ) 7.5, 1.8 Hz, 1H), 6.52 (dd, J ) 14.1, 6.6 Hz, 1H), 4.66
(s, 2H), 4.42 (dd, J ) 14.1, 2.4 Hz, 1H), 4.17 (dd, J ) 6.6, 2.4
Hz, 1H); 13C NMR δ 150.4, 138.7, 133.0, 129.8, 128.8, 127.7,
100.7, 88.7, 88.6, 87.4, 56.5; HRMS (EI) m/ z calcd for C11H9-
IO (M+) 283.9697, found 283.9668.
P r ep a r a tion of Meth yl 7-(2-Iod op h en yl)h ep t-2-en -6-
yn oa te (11). To a stirred solution of 10 (1.50 g, 5.24 mmol)
in dichloromethane (150 mL) was added pyridinium chloro-
chromate (1.36 g, 6.30 mmol). The reaction mixture was
stirred overnight at room temperature, upon which the alcohol
was consumed as monitored by TLC. The solvent was removed
in vacuo, and the residue was filtered through silica gel using
a 2:1 mixture of hexanes/ethyl acetate. The filtrate was
concentrated, and the residue was subjected to radial chro-
matography (9:1 hexanes/ethyl acetate) to give 5-(2-iodophen-
yl)-4-pentynal as a light yellow oil (1.16 g, 78%): TLC Rf 0.34
(5:1 hexanes/ethyl acetate); IR (neat) ν 3059, 2107, 1723, 1473,
1
756 cm-1; H NMR δ 9.82 (t, J ) 1.2 Hz, 1H), 7.75 (dd, J )
7.5, 1.5 Hz, 1H), 7.36 (dd, J ) 7.5, 1.5 Hz, 1H), 7.20 (td, J )
7.5, 1.5 Hz, 1H), 6.90 (td, J ) 7.5, 1.5 Hz, 1H), 2.72 (td, J )
7.2, 1.2 Hz, 2H), 2.55 (t, J ) 7.2 Hz, 2H); 13C NMR δ 202.0,
138.6, 132.6, 130.4, 129.1, 127.3, 101.5, 94.1, 83.5, 43.1, 21.4;
HRMS (EI) calcd for C11H9IO (M+) 283.9697, found 283.9695.
To a stirred mixture of trimethyl phosphonoacetate (0.340
mL, 2.10 mmol) and lithium chloride (0.120 g, 2.83 mmol) in
acetonitrile (10 mL) was added 1,8-diazabicyclo[5.4.0]undec-
7-ene (DBU) (0.320 mL, 2.14 mmol) at room temperature
under nitrogen. The reaction mixture was stirred at room
temperature for 30 min. 5-(2-Iodophenyl)-4-pentynal (0.400
g, 1.41 mmol), dissolved in acetonitrile (10 mL), was then
added dropwise via syringe into the reaction mixture. The
reaction mixture was stirred at room temperature overnight,
upon which the aldehyde was consumed as monitored by TLC.
The reaction mixture was extracted with diethyl ether/water.
The organic phase was dried over magnesium sulfate, filtered,
and concentrated in vacuo. Purification of the product was
achieved by radial chromatography (95:5 hexanes/ethyl ac-
etate) to afford 11 as a yellow oil (0.408 g, 85%): TLC Rf 0.45
(5:1 hexanes/ethyl acetate); IR (neat) ν 2255, 1733, 1659, 1273
2-Iodo-1-[3-(vinyloxy)-1-propynyl]benzene (0.094 g, 0.330
mmol) was subjected to palladium coupling conditions similar
to those for the preparation of 8 using triethylamine (0.140
mL, 1.00 mmol), bis(triphenylphosphine)palladium(II) chloride
1
cm-1; H NMR δ 7.79 (dd, J ) 7.8, 1.2 Hz, 1H), 7.37 (dd, J )
7.8, 1.2 Hz, 1H), 7.23 (td, J ) 7.8, 1.2 Hz, 1H), 7.10 (dt, J )
15.6, 6.6 Hz, 1H), 6.93 (td, J ) 7.8, 1.2 Hz, 1H), 5.96 (dt, J )
15.6, 1.5 Hz, 1H), 3.71 (s, 3H), 2.65-2.48 (m, 4H); 13C NMR δ
166.7, 146.8, 138.5, 132.4, 129.9, 128.9, 127.6, 122.2, 100.8,
(28) General experimental techniques are described in ref 7d.

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 615
92.4, 83.8, 51.4, 31.0, 18.5; HRMS (EI) calcd for C14H13IO2 (M+)
339.9959, found 339.9962.
25.7, 18.2, -5.2, -5.2; HRMS (EI) calcd for C12H14IO2Si (M+
- C4H9) 344.9806, found 344.9795.
P r ep a r a tion of 4-((ter t-bu tyld im eth ylsilyl)oxy)-1-(2-
eth yn ylp h en yl)-2-bu tyn yl 1-Vin yl Eth er (15). Alcohol 14
(0.530 g, 1.32 mmol) was subjected to palladium coupling
reaction conditions similar to those for the preparation of 8
using triethylamine (0.550 mL, 3.96 mmol), bis(triphenylphos-
phine)palladium(II) chloride (0.046 g, 0.066 mmol), copper(I)
iodide (0.025 g, 0.130 mmol), and (trimethylsilyl)acetylene
(0.280 mL, 1.98 mmol). The reaction mixture was allowed to
stir at room temperature under nitrogen for 12 h. The mixture
was filtered through silica gel using a 2:1 mixture of hexanes/
ethyl acetate and evaporated. Purification by radial chroma-
tography (9:1 hexanes/ethyl acetate) provided 4-((tert-butyldi-
methylsilyl)oxy)-1-[[2-(trimethylsilyl)ethynyl]phenyl]-2-butyn-
1-ol as a yellow oil (0.450 g, 92%): TLC Rf 0.52 (3:1 hexanes/
P r ep a r a tion of Meth yl 7-[2-(3-(Vin yloxy)-1-p r op yn yl)-
p h en yl]h ep t-2-en -6-yn oa te (12). Ester 11 (0.290 g, 0.850
mmol) was subjected to reaction conditions similar to those
for the preparation of 8 using triethylamine (0.370 mL, 26.5
mmol), bis(triphenylphosphine)palladium(II) chloride (0.031 g,
0.044 mmol), copper(I) iodide (0.017 g, 0.089 mmol), and
propargyl alcohol (0.077 mL, 1.32 mmol). The reaction mixture
was stirred at 50 °C overnight under nitrogen. The mixture
was passed through silica gel (1:2 hexanes/ethyl acetate), and
the solvent was removed in vacuo. Purification by radial
chromatography (5:1 hexanes/ethyl acetate) provided methyl
7-[2-(3-hydroxy-1-propynyl)phenyl]hept-2-en-6-ynoate as a yel-
low oil (0.202 g, 88%): TLC Rf 0.18 (2:1 hexanes/ethyl acetate);
IR (neat) ν 3430, 2249, 1721, 1659 cm-1; 1H NMR δ 7.40-7.30
(m, 2H), 7.22-7.09 (m, 3H), 5.94 (dt, J ) 15.6, 1.5 Hz, 1H),
ethyl acetate); IR (neat) ν 3455, 2158, 1252, 1084 cm-1 1H
;
4.50 (s, 2H), 3.69 (s, 3H), 3.28 (bs, 1H), 2.62-2.42 (m, 4H); 13
C
NMR δ 7.64 (ddd, J ) 7.5, 1.5, 0.6 Hz, 1H), 7.45 (ddd, J ) 7.5,
1.5, 0.6 Hz, 1H), 7.33 (td, J ) 7.5, 1.5 Hz, 1H), 7.24 (td, J )
7.5, 1.5 Hz, 1H), 5.86 (dt, J ) 5.4, 1.8 Hz, 1H), 4.37 (d, J ) 1.8
Hz, 2H), 2.81 (d, J ) 5.4 Hz, 1H), 0.87 (s, 9H), 0.25 (s, 9H),
0.07 (s, 3H), 0.06 (s, 3H); 13C NMR δ 142.6, 132.6, 129.0, 128.0,
126.6, 121.1, 102.2, 100.4, 85.2, 83.7, 63.1, 51.8, 25.7, 18.2,
-0.2, -5.2; HRMS (EI) calcd for C21H32O2Si2 (M+) 372.1940,
found 372.1939.
NMR δ 167.4, 147.6, 132.1, 131.8, 127.9, 127.4, 125.8, 125.1,
121.8, 92.2, 91.3, 83.6, 80.4, 51.6, 51.2, 31.0, 18.5; HRMS (EI)
calcd for C17H16O3 (M+) 268.1099, found 268.1099.
Compound 12 was prepared by the same ethylenation used
for the preparation of 9 using 7-[2-(3-hydroxy-1-propynyl)-
phenyl]hept-2-en-6-ynoate (0.140 g, 0.520 mmol) and mercury-
(II) acetate (0.051 g, 0.160 mmol) in ethyl vinyl ether (10 mL)
(reflux 2 d). The reaction mixture was passed through Florisil
using a 2:1 mixture of hexanes/ethyl acetate. The solvent was
removed in vacuo, and purification was achieved by column
chromatography (90:9:1 hexanes/ethyl acetate/triethylamine)
to give 12 as a light yellow oil (0.120 g, 78%, two conformers,
2:1 ratio): TLC Rf 0.55 (2:1 hexanes/ethyl acetate); IR (neat)
A mixture of 4-((tert-butyldimethylsilyl)oxy)-1-[[2-(trimeth-
ylsilyl)ethynyl]phenyl]-2-butyn-1-ol (0.333 g, 0.900 mmol) and
mercury(II) acetate (0.086 g, 0.270 mmol) in ethyl vinyl ether
(25 mL) was heated to reflux under nitrogen for 2 d. The
reaction mixture was passed through Florisil using a 2:1
mixture of hexanes/ethyl acetate. The solvent was removed
in vacuo, and the residue was subjected to column chroma-
tography (94:5:1 hexanes/ethyl acetate/triethylamine) to yield
4-((tert-butyldimethylsilyl)oxy)-1-[(2-(trimethylsilyl)ethynyl)-
phenyl]-2-butynyl 1-vinyl ether as a yellow oil (0.180 g, 50%):
TLC Rf 0.65 (5:1 hexanes/ethyl acetate); IR (neat) ν 2158, 1616,
ν 2255, 1725, 1661, 1626, 1273 cm-1 1H NMR δ 7.45-7.33
;
(m, 2H), 7.26-7.15 (m, 2H), 7.05 (dt, J ) 15.6, 6.6 Hz, 1H),
6.52 (dd, J ) 14.1, 6.6 Hz, 1/3H), 6.50 (dd, J ) 14.1, 6.6 Hz,
2/3H), 5.93 (dt, J ) 15.6, 1.5 Hz, 1H), 4.65 (s, 2H), 4.39 (dd, J
) 14.1, 2.7 Hz, 1/3H), 4.38 (dd, J ) 14.1, 2.7 Hz, 2/3H), 4.15
(dd, J ) 6.6, 2.7 Hz, 1/3H), 4.13 (dd, J ) 6.6, 2.7 Hz, 2/3H), 3.71
(s, 2H), 3.69 (s, 1H), 2.80-2.45 (m, 4H); 13C NMR δ 166.8,
150.5, 147.0, 132.1, 132.0, 131.9, 131.8, 128.3, 127.5, 126.1,
124.7, 122.0, 92.6, 88.4, 87.1, 85.8, 80.1, 56.7, 51.8, 51.5, 33.3,
31.3, 18.6; HRMS (EI) calcd for C19H18O3 (M+) 294.1256, found
294.1251.
1
1252, 1094 cm-1; H NMR δ 7.70 (ddd, J ) 7.5, 1.5, 0.6 Hz,
1H), 7.46 (ddd, J ) 7.5, 1.5, 0.6 Hz, 1H), 7.35 (td, J ) 7.5, 1.5
Hz, 1H), 7.26 (td, J ) 7.5, 1.5 Hz, 1H), 6.49 (dd, J ) 14.4, 6.9
Hz, 1H), 6.00 (t, J ) 1.8 Hz, 1H), 4.48 (dd, J ) 14.4, 1.8 Hz,
1H), 4.39 (d, J ) 1.8 Hz, 2H), 4.16 (dd, J ) 6.9, 1.8 Hz, 1H),
0.88 (s, 9H), 0.25 (s, 9H), 0.08 (s, 3H), 0.08 (s, 3H); 13C NMR
δ 150.0, 139.6, 132.3, 129.0, 128.5, 127.4, 122.2, 101.9, 100.1,
89.9, 86.7, 81.4, 68.4, 51.7, 25.7, 18.2, -0.1, -5.2; HRMS (EI)
calcd for C23H34O2Si2 (M+) 398.2098, found 398.2115.
P r ep a r a tion of 4-((ter t-Bu tyld im eth ylsilyl)oxy)-1-(2-
iod op h en yl)-2-bu tyn -1-ol (14). 2-Iodobenzyl alcohol (13)
(10.0 g, 43.0 mol) was subjected to PCC oxidation conditions
(PCC, 11.1 g, 51.6 mmol) similar to those for the preparation
of 11. After the reaction was complete, the solvent was
removed in vacuo and the residue was filtered through silica
gel using a 2:1 mixture of hexanes/ethyl acetate to give
2-iodobenzaldehyde as a colorless crystalline solid (9.67g,
97%): TLC Rf 0.55 (3:1 hexanes/ethyl acetate); IR (neat) ν
To a stirred solution of 4-((tert-butyldimethylsilyl)oxy)-1-[(2-
(trimethylsilyl)ethynyl)phenyl]-2-butynyl 1-vinyl ether (0.090
g, 0.230 mmol) in methanol (15 mL) was added a catalytic
amount of potassium carbonate. The resulting mixture was
allowed to stir at room temperature for 2 h. Subsequently,
the mixture was filtered through Florisil using a 3:1 mixture
of hexanes/ethyl acetate. The solvent was removed in vacuo,
and the residue was subjected to column chromatography (94:
5:1 hexanes/ethyl acetate/triethylamine) to afford 15 as a
yellow oil (0.056 g, 75%): TLC Rf 0.55 (5:1 hexanes/ethyl
1
1696, 1200, 754 cm-1; H NMR δ 10.01 (d, J ) 0.6 Hz, 1H),
7.91-7.80 (m, 2H), 7.44-7.20 (m, 2H); 13C NMR δ 195.6, 140.5,
135.4, 135.0, 130.1, 128.6, 100.7; HRMS (EI) calcd for C7H5IO
(M+) 231.9384, found 231.9390.
1
acetate); IR (neat) ν 3298, 1640, 1256, 1092 cm-1; H NMR δ
To a stirred solution of tert-butyldimethylsilyl propargyl
ether (2.20 g, 13.0 mmol) in THF (10 mL) at -20 °C (sodium
chloride/ice bath) was added n-butyllithium (2.5 M solution
in hexanes) (5.20 mL, 13.0 mmol) via syringe. After 30 min,
2-iodobenzaldehyde (2.00 g, 8.60 mmol), dissolved in THF (15
mL), was added via syringe into the reaction mixture. The
mixture was allowed to warm to room temperature and stirred
overnight. The reaction was quenched with a saturated
aqueous sodium chloride solution followed by removal of THF
in vacuo to give a residue which was extracted with dichlo-
romethane. The organic layer was dried over magnesium
sulfate, filtered, and evaporated. Purification by radial chro-
matography (95:5 hexanes/ethyl acetate) afforded 14 as a
colorless oil (2.77g, 80%): TLC Rf 0.50 (3:1 hexanes/ethyl
7.70 (dd, J ) 7.5, 1.5 Hz, 1H), 7.50 (dd, J ) 7.5, 1.5 Hz, 1H),
7.39 (td, J ) 7.5, 1.5 Hz, 1H), 7.29 (td, J ) 7.5, 1.5 Hz, 1H),
6.48 (dd, J ) 14.1, 6.6 Hz, 1H), 5.99 (t, J ) 1.8 Hz, 1H), 4.47
(dd, J ) 14.1, 2.1 Hz, 1H), 4.37 (d, J ) 1.8 Hz, 2H), 4.15 (dd,
J ) 6.6, 2.1 Hz, 1H), 3.33 (s, 1H), 0.87 (s, 9H), 0.07 (s, 3H),
0.07 (s, 3H);
121.0, 90.3, 86.8, 82.5, 81.3, 80.6, 68.4, 51.7, 25.7, 18.2, -5.2;
HRMS (EI) calcd for C20H26O2Si (M+) 326.1702, found 326.1694.
P r ep a r a tion of 5-[2-(1-Acetoxy-4-((ter t-bu tyld im eth yl-
silyl)oxy)-2-bu tyn yl)p h en yl]-4-p en tyn -1-ol (16). Alcohol
14 (2.00 g, 4.98 mmol) was dissolved in dichloromethane (25
mL); then triethylamine (3.50 mL, 25.0 mmol) and acetic
anhydride (0.940 mL, 9.96 mmol) were added via syringe. The
reaction mixture was allowed to stir at room temperature for
7 h, upon which the alcohol was consumed as monitored by
TLC. The mixture was extracted with dichloromethane/water.
The organic layer was dried over magnesium sulfate followed
by filtration and evaporation to give a yellow oil. Purification
by radial chromatography (95:5 hexanes/ethyl acetate) yielded
4-((tert-butyldimethylsilyl)oxy)-1-(2-iodophenyl)-2-butynyl-1-
13C NMR δ 149.7, 139.9, 132.8, 129.3, 128.5, 127.4,
1
acetate); IR (neat) ν 3391, 2343, 1084, 837 cm-1; H NMR δ
7.80 (dd, J ) 7.8, 1.2 Hz, 1H), 7.72 (dd, J ) 7.8, 1.8 Hz, 1H),
7.36 (td, J ) 7.5, 1.2 Hz, 1H), 6.99 (td, J ) 7.5, 1.8 Hz, 1H),
5.68-5.62 (m, 1H), 4.36 (d, J ) 1.8 Hz, 2H), 2.67 (d, J ) 4.8
Hz, 1H), 0.87 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H); 13C NMR δ
142.4, 139.6, 130.0, 128.6, 128.1, 97.9, 85.6, 83.6, 68.4, 51.8,

616 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
acetate as a yellow oil (1.80 g, 82%): TLC Rf 0.64 (2:1 hexanes/
chromatography of the resulting oil (3:1 hexanes/diethyl ether)
gave methyl 7-[2-(1-hydroxy-4-((tert-butyldimethylsilyl)oxy)-
2-butynyl)phenyl]hept-2-en-6-ynoate as a light yellow oil (0.190
g, 95%): TLC Rf 0.34 (2:1 hexanes/ethyl acetate); IR (neat) ν
3435, 2232, 1726, 1660 cm-1; 1H NMR δ 7.65 (dd, J ) 7.5, 1.5
Hz, 1H), 7.37 (dd, J ) 7.5, 1.2 Hz, 1H), 7.29 (td, J ) 7.5, 1.5
Hz, 1H), 7.22 (td, J ) 7.5, 1.5 Hz, 1H), 7.05 (dt, J ) 15.6, 6.6
Hz, 1H), 5.95 (dt, J ) 15.6, 1.5 Hz, 1H), 5.87-5.82 (m, 1H),
4.36 (d, J ) 1.8 Hz, 2H), 3.72 (s, 3H), 2.93 (d, J ) 5.1 Hz, 1H),
1
ethyl acetate); IR (neat) ν 1748, 1223, 1088 cm-1; H NMR δ
7.83 (dd, J ) 7.8, 1.2 Hz, 1H), 7.72 (dd, J ) 7.8, 1.8 Hz, 1H),
7.37 (td, J ) 7.8, 1.2 Hz, 1H), 7.02 (td, J ) 7.8, 1.8, 1H), 6.52
(t, J ) 1.8 Hz, 1H), 4.36 (d, J ) 1.8 Hz, 2H), 2.09 (s, 3H), 0.87
(s, 9H), 0.08 (s, 3H), 0.07 (s, 3H); 13C NMR δ 169.3, 139.7,
139.1, 130.5, 129.3, 128.5, 98.4, 86.7, 80.5, 69.6, 51.7, 25.7, 20.8,
18.2, -5.2; HRMS (EI) calcd for C14H16IO3Si (M+ - C4H9)
386.9912, found 386.9919.
2.65-2.45 (m, 4H), 0.86 (s, 9H), 0.06 (s, 3H), 0.06 (s, 3H); 13
C
4-((tert-Butyldimethylsilyl)oxy)-1-(2-iodophenyl)-2-butyne-1-
acetate (1.58 g, 3.56 mmol) was subjected to palladium
coupling reaction conditions similar to those for the prepara-
tion of 8 using triethylamine (1.50 mL, 10.7 mmol), bis-
(triphenylphosphine)palladium(II) chloride (0.125 g, 0.180
mmol), copper(I) iodide (0.068 g, 0.360 mmol), and 4-pentynol
(0.500 mL, 5.37 mmol). The reaction mixture was allowed to
stir at room temperature for 2 d. Then the mixture was passed
through silica gel using a 1:2 mixture of hexanes/ethyl acetate
and the solvent was removed in vacuo. Purification by radial
chromatography (5:1 hexanes/ethyl acetate) provided 16 as a
yellow oil (0.450 g, 32%): TLC Rf 0.20 (2:1 hexanes/ethyl
NMR δ 167.0, 147.0, 142.0, 132.3, 128.3, 128.1, 126.7, 122.2,
121.7, 93.6, 84.9, 84.1, 79.2, 62.8, 51.8, 51.6, 31.0, 25.7, 18.6,
18.2, -5.3; HRMS (EI) calcd for C20H23O4Si (M+ - C4H9)
355.1366, found 355.1366.
Compound 17 was prepared by the same ethylenation used
for the preparation of 9 using 7-[2-(1-hydroxy-4-((tert-bu-
tyldimethylsilyl)oxy)-2-butynyl)phenyl]hept-2-en-6-ynoate (0.190
g, 0.460 mmol) and mercury(II) acetate (0.044 g, 0.140 mmol)
in ethyl vinyl ether (10 mL) (reflux 1 d) to give 17 as a colorless
oil (0.132 g, 66%): TLC Rf 0.62 (2:1 hexanes/ethyl acetate);
IR (neat) ν 2268, 1728, 1660, 1638, 1256 cm-1; 1H NMR δ 7.65
(dd, J ) 7.5, 1.5 Hz, 1H), 7.37 (dd, J ) 7.5, 1.2 Hz, 1H), 7.31
(td, J ) 7.5, 1.5 Hz, 1H), 7.23 (td, J ) 7.5, 1.5 Hz, 1H), 7.01
(dt, J ) 15.6, 6.6 Hz, 1H), 6.46 (dd, J ) 14.1, 6.6 Hz, 1H), 5.93
(dt, J ) 15.6, 1.5 Hz, 1H), 5.92 (t, J ) 1.8 Hz, 1H), 4.44 (dd, J
) 14.1, 2.1 Hz, 1H), 4.36 (d, J ) 1.8 Hz, 2H), 4.12 (dd, J )
6.6, 2.1 Hz, 1H), 3.71 (s, 3H), 2.63-2.46 (m, 4H), 0.85 (s, 9H),
0.06 (s, 3H), 0.06 (s, 3H); 13C NMR δ 166.7, 149.8, 146.8, 139.0,
132.2, 128.4, 128.3, 127.3, 122.5, 122.2, 93.8, 90.0, 86.6, 81.4,
78.7, 68.5, 51.7, 51.4, 31.2, 25.7, 18.5, 18.2, -5.2; HRMS (EI)
calcd for C26
acetate); IR (neat) ν 3425, 2230, 1744, 1227, 1084 cm-1 1H
;
NMR δ 7.70 (dd, J ) 7.5, 1.8 Hz, 1H), 7.38 (dd, J ) 7.5, 1.5
Hz, 1H), 7.31 (td, J ) 7.5, 1.8 Hz, 1H), 7.26 (td, J ) 7.5, 1.5
Hz, 1H), 6.87 (t, J ) 1.8 Hz, 1H), 4.37 (d, J ) 1.8 Hz, 2H),
3.85-3.70 (m, 2H), 2.54 (t, J ) 6.6 Hz, 2H), 2.19 (bs, 1H), 2.07
(s, 3H), 1.81 (quintet, J ) 6.6 Hz, 2H), 0.87 (s, 9H), 0.08 (s,
3H), 0.08 (s, 3H); 13C NMR δ 169.9, 138.0, 132.1, 128.8, 128.0,
127.8, 123.2, 95.4, 86.0, 80.9, 77.8, 64.0, 61.1, 51.7, 31.0, 25.7,
20.8, 18.2, 15.8, -5.2, -5.3; HRMS (EI) calcd for C19H23O4Si
(M+ - C4H9) 343.1366, found 343.1370.
H34O4Si (M+) 438.2226, found 438.2211.
P r ep a r a tion of Meth yl 7-[2-(1-(Vin yloxy)-4-((ter t-bu tyl-
d im eth ylsilyl)oxy)-2-bu tyn yl) p h en yl]h ep t-2-en -6-yn oa te
(17). To a stirred solution of 16 (0.420 g, 1.05 mmol) in
dichloromethane (25 mL) was added pyridinium chlorochro-
mate (0.340 g, 1.58 mmol). The resulting mixture was stirred
at room temperature overnight, upon which the reaction
mixture was filtered through silica gel using a 1:1 mixture of
hexanes/ethyl acetate. The solvent was removed in vacuo, and
the residue was subjected to radial chromatography (5:1
hexanes/ethyl acetate) to afford 5-[2-(1-acetoxy-4-((tert-bu-
tyldimethylsilyl)oxy)-2-butynyl)phenyl]-4-pentynal as a pale
yellow oil (0.350 g, 84%): TLC Rf 0.42 (2:1 hexanes/ethyl
acetate); IR (neat) ν 2230, 1746, 1732 cm-1; 1H NMR δ 9.80 (t,
J ) 0.9 Hz, 1H), 7.70 (dd, J ) 7.5, 1.8 Hz, 1H), 7.37 (dd, J )
7.5, 1.5 Hz, 1H), 7.30 (td, J ) 7.5, 1.8 Hz, 1H), 7.25 (td, J )
7.5, 1.5 Hz, 1H), 6.81 (t, J ) 1.8 Hz, 1H), 4.36 (d, J ) 1.8 Hz,
2H), 2.80-2.66 (m, 4H), 2.05 (s, 3H), 0.86 (s, 9H), 0.07 (s, 3H),
0.06 (s, 3H); 13C NMR δ 200.2, 169.5, 138.0, 132.1, 128.7, 128.2,
127.8, 122.8, 93.7, 86.0, 80.9, 78.1, 63.7, 51.7, 42.3, 25.7, 20.8,
18.1, 12.6, -5.3; HRMS (EI) calcd for C19H21O4Si (M+ - C4H9)
341.1209, found 341.1225.
P r ep a r a tion of 1-(2-Hyd r oxyeth yl)-2-m eth yln a p h th a -
len e (20′) a n d 1,3-Dih yd r o-1-m eth ylben z[e]isoben zofu -
r a n (23) via Th er m a l Cycliza tion of En ed iyn e 9.
A
solution of vinyl ether 9 (0.056 g, 0.310 mmol) in anhydrous
chlorobenzene (7.3 mL) was transferred to a predried high-
pressure vial. The reaction mixture was degassed by passing
dry nitrogen through the solution for 20 min, and 1,4-CHD
(1.70 mL, 18.0 mmol) was added via syringe. The reaction
vial was sealed under nitrogen with a nylon screw cap and
heated to 150 °C for 8 h, upon which the starting material
was consumed as monitored by TLC. Removal of the solvent
in vacuo followed by radial chromatography of the residue
(pentane followed by 98:2 pentane/ethyl acetate) gave a
mixture of aldehyde 20 and ether 23 as a colorless oil (0.032
g, 3:1 ratio, 56% combined yield). To a stirred solution of 20
and 23 in methanol (4 mL) was added sodium borohydride
(0.013 g, 0.340 mmol). The stirring was continued for 2 h, and
the reaction mixture was passed through Florisil (2:1 hexanes/
ethyl acetate). The solvent was removed in vacuo, and the
residue was subjected to radial chromatography (95:5 hexanes/
ethyl acetate) to provide the reduced product of aldehyde 20
(alcohol 20′) (0.022 g, 38% from 9) and ether 23 (0.008 g, 14%
5-[2-(1-Acetoxy-4-((tert-butyldimethylsilyl)oxy)-2-butynyl)-
phenyl]-4-pentynal (0.680 g, 1.70 mmol) was subjected to
Horner-Emmons reaction conditions similar to those for the
preparation of 11, and the reaction was worked up similarly.
Purification was achieved by radial chromatography (9:1
hexanes/ethyl acetate) to provide methyl 7-[2-(1-acetoxy-4-
((tert-butyldimethylsilyl)oxy)-2-butynyl)phenyl]hept-2-en-6-
ynoate as a light yellow oil (0.667 g, 86%): TLC Rf 0.48 (2:1
hexanes/ethyl acetate); IR (neat) ν 2232, 1742, 1726, 1660
from 9) as colorless oils. 20′: TLC Rf
0.22 (2:1 hexanes/ethyl
acetate); IR (neat) ν 3356, 2860, 1040 cm-1; H NMR δ 8.06
(d, J ) 8.1 Hz, 1H), 7.80 (dd, J ) 8.1, 1.5 Hz, 1H), 7.65 (d, J
) 8.1 Hz, 1H), 7.49 (ddd, J ) 8.4, 6.9, 1.5 Hz, 1 H), 7.40 (ddd,
J ) 7.8, 6.9, 1.5 Hz, 1H), 7.30 (d, J ) 8.4 Hz, 1H), 3.91 (t, J )
7.5 Hz, 2H), 3.40 (t, J ) 7.5 Hz, 2H), 2.53 (s, 3H), 1.49 (bs,
1H); 13C NMR δ 134.3, 132.5, 131.0, 130.5, 129.2, 128.6, 126.8,
126.1, 124.6, 123.5, 62.5, 31.8, 20.5; HRMS (EI) calcd for
1
cm-1; H NMR δ 7.70 (dd, J ) 7.5, 1.8 Hz, 1H), 7.37 (dd, J )
C13
H14O (M+) 186.1045, found 186.1051. 23: TLC Rf 0.65 (2:1
1
7.5, 1.5 Hz, 1H), 7.31 (td, J ) 7.5, 1.8 Hz, 1H), 7.26 (td, J )
7.5, 1.5 Hz, 1H), 6.99 (dt, J ) 15.6, 6.6 Hz, 1H), 6.82 (t, J )
1.8 Hz, 1H), 5.91 (dt, J ) 15.6, 1.5 Hz, 1H), 4.36 (d, J ) 1.8
Hz, 2H), 3.70 (s, 3H), 2.60-2.44 (m, 4H), 2.05 (s, 3H), 0.86 (s,
9H), 0.07 (s, 3H), 0.06 (s, 3H); 13C NMR δ 169.4, 166.7, 146.8,
138.1, 132.2, 128.7, 128.1, 127.8, 122.8, 122.1, 94.1, 86.0, 80.9,
78.3, 63.8, 51.7, 51.4, 31.1, 25.7, 20.7, 18.4, 18.1, -5.3; HRMS
(EI) calcd for C22H25O5Si (M+ - C4H9) 397.1471, found 397.1462.
To a stirred solution of 7-[2-(1-acetoxy-4-((tert-butyldimeth-
ylsilyl)oxy)-2-butynyl)phenyl]hept-2-en-6-ynoate (0.220 g, 0.480
mmol) in methanol (12 mL) was added a catalytic amount of
potassium carbonate. The reaction mixture was stirred at
room temperature for 6 h; then the mixture was passed
through Florisil with diethyl ether and concentrated. Radial
hexanes/ethyl acetate); IR (neat) ν 3057, 2859, 1067, 810 cm-1
;
1H NMR δ 7.90 (dd, J ) 7.5, 1.8 Hz, 1H), 7.80-7.70 (m, 2H),
7.56-7.42 (m, 2H), 7.33 (d, J ) 8.1 Hz, 1H), 5.91-5.80 (m,
1H), 5.35 (dd, J ) 12.3, 3.3 Hz, 1H), 5.19 (dd, J ) 12.3, 1.5
Hz, 1H), 1.65 (d, J ) 6.0 Hz, 3H); 13C NMR δ 138.3, 135.8,
133.2, 128.8, 128.6, 128.5, 126.5, 125.3, 123.5, 119.2, 80.7, 73.1,
22.2; HRMS (EI) calcd for C13
184.0887.
H12O (M+) 184.0888, found
P r ep a r a tion of Meth yl 2,3-Dih yd r o-5-(for m ylm eth yl)-
4-m eth yl-1H-ben z[e]in d en e-1-a ceta te (25) via Ta n d em
En yn e Allen e-Ra d ica l Cycliza tion of En ed iyn e 12.
A
solution of vinyl ether 12 (0.050 g, 0.170 mmol) in anhydrous
chlorobenzene (7.3 mL) was transferred to a predried high-
pressure vial. The reaction mixture was degassed by passing

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 617
dry nitrogen through the solution for 20 min, and 1,4-CHD
(1.70 mL, 18.0 mmol) was added via syringe. The reaction
vial was sealed under nitrogen with a nylon screw cap and
heated to 150 °C for 8 h, upon which the starting material
was consumed as monitored by TLC. The solvent was removed
in vacuo, and the residue was subjected to radical chromatog-
raphy (95:5 hexanes/ethyl acetate) to afford 25 as a pale yellow
oil (0.010 g, 20%): TLC Rf 0.42 (2:1 hexanes/ethyl acetate);
IR (neat) ν 2949, 1726, 1437, 1273 cm-1; 1H NMR δ 9.71 (t, J
) 2.1 Hz, 1H), 7.95-7.80 (m, 2H), 7.50-7.40 (m, 2H), 4.17 (d,
J ) 2.1 Hz, 2H), 4.22-4.10 (m, 1H), 3.72 (s, 3H), 3.19-2.96
(m, 2H), 2.77 (dd, J ) 15.3, 3.3 Hz, 1H), 2.40 (s, 3H), 2.37 (dd,
J ) 15.3, 11.1 Hz, 2H), 2.16-2.06 (m, 1H); 13C NMR δ 199.3,
173.3, 141.1, 140.6, 132.7, 132.4, 128.4, 125.7, 125.4, 124.8,
124.5, 124.2, 51.7, 44.0, 40.9, 38.7, 31.1, 30.3, 17.1; HRMS (EI)
calcd for C19H20O3 (M+) 296.1413, found 296.1420.
(2:1 hexanes/ethyl acetate); IR (neat) ν 2236, 1954, 1726, 1660,
1
1260 cm-1; H NMR δ 9.72 (t, J ) 2.1 Hz, 1H), 7.39 (dd, J )
7.8, 0.9 Hz, 1H), 7.34 (dd, J ) 7.8, 0.9 Hz, 1H), 7.19 (td, J )
7.8, 0.9 Hz, 1H), 7.09 (td, J ) 7.8, 0.9 Hz, 1H), 7.02 (dt, J )
15.6, 6.6 Hz, 1H), 6.80 (tt, J ) 2.1, 2.4 Hz, 1H), 5.92 (dt, J )
15.6, 1.5 Hz, 1H), 4.27 (d, J ) 2.4 Hz, 2H), 3.70 (s, 3H), 3.20-
3.17 (m, 2H), 2.64-2.46 (m, 4H), 0.86 (s, 9H), 0.04 (s, 3H), 0.03
(s, 3H); 13C NMR δ 203.9, 199.4, 166.7, 146.8, 135.1, 132.5,
128.0, 126.9, 126.5, 122.1, 121.6, 100.5, 94.5, 93.2, 79.6, 63.9,
51.4, 43.9, 31.3, 25.7, 18.5, 18.2, -5.5, -5.5; HRMS (EI) calcd
for C26H34O4Si (M+) 438.2226, found 438.2218.
P r ep a r a tion of 33a ,b via Ta n d em En yn e Allen e-
Ra d ica l Cycliza tion of 31. A solution of allene 31 (0.059 g,
0.135 mmol) in anhydrous chlorobenzene (7.3 mL) was trans-
ferred to a predried high-pressure vial. The reaction mixture
was degassed by passing dry nitrogen through the solution
for 20 min, and 1,4-CHD (1.70 mL, 18.0 mmol) was added via
syringe. The reaction vial was sealed under nitrogen with a
nylon screw cap and heated to 75 °C for 8 h, upon which the
reaction was complete as monitored by TLC. The solvent was
removed in vacuo, and the residue was subjected to radial
chromatography (98:2 hexanes/ethyl acetate) to afford 33a
(0.023 g) and 33b (0.025 g) as pale yellow oils (1:1 diastero-
meric ratio, 80% combined yield).
P r epar ation of 3-[((ter t-Bu tyldim eth ylsilyl)oxy)m eth yl]-
3-(2-n a p h th yl)p r op a n a l (30) via Ta n d em [3,3] Sigm a tr o-
p ic Rea r r a n gem en t -En yn e Allen e Cycliza tion of Diyn e
15. A solution of vinyl ether 15 (0.045 g, 0.140 mmol) was
thermolyzed at 150 °C for 4.5 h in the same manner as that of
12. Radial chromatography (9:1 hexanes/ethyl acetate) gave
30 as a pale yellow oil (0.021 g, 45%): TLC Rf 0.44 (5:1
hexanes/ethyl acetate); IR (neat) ν 1726, 1472, 1256, 1094
1
cm-1; H NMR δ 9.76 (t, J ) 2.1 Hz, 1H), 7.81-7.75 (m, 3H),
P r ep a r a tion of 4-((ter t-Bu tyld im eth ylsilyl)oxy)-1-(2-
eth yn ylp h en yl)bu t-2-yn -1-ol (34). Alcohol 14 (0.505 g 1.23
mmol) was subjected to coupling conditions similar to those
for the preparation of 8 using triethylamine (0.60 mL, 0.37 g,
3.7 mmol), bis(triphenylphosphine)palladium(II) chloride
(0.041g, 0.06 mmol), copper(I) iodide (0.023g, 0.12 mmol), and
(trimethylsilyl)acetylene (0.23 mL, 0.16 g, 1.6 mmol). The
reaction was stirred for 3 h. Catalytic potassium carbonate
resulted in desilylation (2 h). The resulting oil was subjected
to column chromatography (80:20 hexanes/ethyl acetate) to
afford product 34 as a yellow oil (0.332 g, 89%): TLC Rf 0.56
(2:1 hexanes/ethyl acetate); IR (neat) ν 3406, 3300, 2930, 1082
7.65 (s, 1H), 7.50-7.40 (m, 2H), 7.34 (dd, J ) 8.7, 1.8 Hz, 1H),
3.85 (dd, J ) 9.9, 4.8 Hz, 1H), 3.70 (dd, J ) 9.9, 8.1 Hz, 1H),
3.57 (dddd, J ) 8.1, 7.2, 6.9, 4.8 Hz, 1H), 3.02 (ddd, J ) 16.8,
7.2, 2.1 Hz, 1H), 2.80 (ddd, J ) 16.8, 6.9, 2.1 Hz, 1H), 0.86 (s,
9H), -0.02 (s, 6H); 13C NMR δ 201.8, 138.6, 133.4, 132.5, 128.3,
127.7, 127.6, 126.4, 126.2, 126.2, 125.7, 67.5, 46.6, 43.0, 25.8,
18.2, -5.6; HRMS (EI) calcd for C20H28O2Si (M+) 327.1780,
found 327.1786.
P r ep a r a t ion of Met h yl 2,3-Dih yd r o-4-[1-(((ter t-b u -
tyld im eth ylsilyl)oxy)m eth yl)-2-for m yleth yl]-1H-ben z[e]-
in d en e-1-a ceta te (33a ,b) via Ta n d em En yn e Allen e-
Ra d ica l Cycliza tion of Diyn e 17. A solution of vinyl ether
17 (0.100 g, 0.230 mmol) was thermolyzed at 150 °C for 7 h in
the same manner as that of 12. Radial chromatography (98:2
hexanes/ethyl acetate) gave 33a and 33b as pale yellow oils
(1:1 diasteromeric ratio, 54% combined yield). 33a (0.026 g):
TLC Rf 0.48 (2:1 hexanes/ethyl acetate); IR (neat) ν 2953, 1730,
1
cm-1; H NMR δ 7.84 (dd, 1H, J ) 7.5, 1.5 Hz), 7.64 (dd, 1H,
J ) 7.5, 1.5 Hz), 7.53 (td, 1H, J ) 7.5, 1.5 Hz), 7.42 (td, 1H, J
) 7.5, 1.5 Hz), 6.04 (dt, 1H, J ) 5.7, 1.8 Hz), 4.52 (d, 2H, J )
1.8 Hz), 3.50 (s, 1H), 2.76 (d, 1H, J ) 5.7 Hz), 1.03 (s, 9H),
0.23 (s, 6H); 13C NMR δ 134.4, 132.1, 130.5, 129.5, 129.4, 127.3,
85.6, 84.5, 81.2, 74.5, 64.1, 52.0, 26.8, 19.1, -1.1; HMRS (EI)
calcd for C18H24O2Si (M+ - C4H9) 243.0841, found 243.0834.
P r ep a r a tion of 7-[2-[4-((ter t-Bu tyld im eth ylsilyl)oxy)-
1437, 1256, 1101 cm-1 1H NMR δ 9.77 (t, J ) 2.1 Hz, 1H),
;
7.85-7.74 (m, 2H), 7.49 (s, 1H), 7.48-7.36 (m, 2H), 4.15 (ddd,
J ) 11.4, 8.1, 3.0 Hz, 1H), 3.86-3.76 (m, 1H), 3.72 (s, 3H),
3.70-3.58 (m, 2H), 3.20-3.10 (m, 2H), 3.05 (ddd, J ) 16.8,
6.6, 2.1 Hz, 1H), 2.84 (ddd, J ) 16.8, 6.6, 2.1 Hz, 1H), 2.78
(dd, J ) 15.3, 2.7 Hz, 1H), 2.37 (dd, J ) 15.3, 11.1Hz, 2H),
2.20-2.08 (m, 1H), 0.85 (s, 9H), -0.03 (s, 3H), -0.04 (s, 3H);
13C NMR δ 203.9, 201.7, 173.3, 141.5, 140.1, 135.9, 133.3,
128.5, 126.0, 125.2, 125.0, 123.5, 66.8, 51.7, 46.6, 40.7, 39.8,
38.6, 30.6, 30.0, 25.8, 18.3, -5.6, -5.5; HRMS (EI) calcd for
C26H36O4Si (M+) 440.2383, found 440.2379. 33b (0.028 g):
TLC Rf 0.48 (2:1 hexanes/ethyl acetate); IR (neat) ν 2953, 1730,
1-h yd r oxy-2-b u t yn yl)p h en yl]h ep t -2-en -6-yn oa t e
(35).
Alcohol 16 (0.316 g, 0.79 mmol) was transferred to an oven-
dried, nitrogen-flushed flask and diluted with dichloromethane
(17 mL). Pyridinium chlorochromate (0.510 g, 2.4 mmol) and
a weight equivalent of Celite were added under vigorous
stirring in a portionwise manner. After 2.5 h, the reaction
mixture was filtered and concentrated. It was then purified
by column chromatograghy (80:20 hexanes/ethyl acetate) to
afford 5-[2-(1-acetoxy-4-((tert-butyldimethylsilyl)oxy)-2-butyn-
yl)phenyl]-4-pentynal (0.20 g, 65%) as a colorless oil: TLC Rf
0.55 (2:1 hexanes/ethyl acetate); IR (neat) ν 2932, 1746, 1732,
840 cm-1; 1H NMR δ 7.63 (dd, 1H, J ) 7.8, 1.5 Hz), 7.16-7.31
(m, 3H), 6.74 (t, 1H, J ) 1.8 Hz), 4.30 (d, 2H, J ) 1.8 Hz),
2.67 (m, 4H), 1.91 (s, 3H), 0.80 (s, 9H), 0.01 (s, 3H), 0.00 (s,
3H); 13C NMR δ 200.3, 169.7, 138.2, 132.4, 128.9, 128.3, 128.0,
122.9, 93.9, 86.2, 81.1, 78.3, 64.0, 52.0, 42.6, 26.0, 21.1, 18.6,
12.9, -1.1; HMRS (EI) calcd for C23H30O4Si (M+ - C4H9)
341.1209, found 341.1225.
1437, 1256, 1101 cm-1 1H NMR δ 9.76 (t, J ) 1.8 Hz, 1H),
;
7.85-7.73 (m, 2H), 7.49 (s, 1H), 7.48-7.36 (m, 2H), 4.15 (ddd,
J ) 11.4, 8.1, 3.0 Hz, 1H), 3.88-3.77 (m, 1H), 3.72 (s, 3H),
3.70-3.58 (m, 2H), 3.30-3.10 (m, 2H), 3.05 (ddd, J ) 16.8,
6.9, 1.8 Hz, 1H), 2.82 (ddd, J ) 16.8, 6.9, 1.8 Hz, 1H), 2.77
(dd, J ) 15.6, 2.7 Hz, 1H), 2.37 (dd, J ) 15.6, 11.4 Hz, 2H),
2.20-2.08 (m, 1H), 0.86 (s, 9H), -0.02 (s, 6H); 13C NMR δ
203.8, 201.6, 173.3, 141.3, 140.2, 136.0, 133.3, 128.4, 126.0,
125.1, 124.9, 123.5, 66.9, 51.7, 46.6, 40.6, 39.6, 38.6, 30.5, 30.0,
25.8, 18.2, -5.5; HRMS (EI) calcd for C26H36O4Si (M+) 440.2383,
found 440.2379.
5-[2-(1-Acetoxy-4-((tert-butyldimethylsilyl)oxy)-2-butynyl)-
phenyl]-4-pentynal (0.131 g, 0.33 mmol) was subjected to
Horner-Emmons reaction conditions similar to those for the
preparation of 11 using trimethyl phosphonoacetate (0.08 mL,
0.09 g, 0.5 mmol), acetonitrile (5 mL), lithium chloride (0.028
g, 0.66 mmol), and DBU (0.07 mL, 0.08 g, 0.5 mmol). The
reaction was stirred 10 min; then the reaction mixture was
passed through silica gel (3:2 hexanes/ethyl acetate) and
subsequently concentrated. The resulting residue was sub-
jected to silica gel chromatography (80:20 hexanes/ethyl
acetate) to afford methyl 7-[2-[1-acetoxy-4-((tert-butyldimeth-
ylsilyl)oxy))-2-butynyl]phenyl]hept-2-en-6-ynoate (0.125g, 86%)
as a slightly yellow oil: TLC Rf 0.56 (3:1 hexanes/ethyl
Meth yl 7-[2-[3-(((ter t-Bu tyld im eth ylsilyl)oxy)m eth yl)-
5-oxo-1,2-p en ta d ien yl]p h en yl]h ep t-2-en -6-yn oa te (31). To
a stirred solution of 17 (0.060 g, 0.140 mmol) in dichlo-
romethane (60 mL) was added a catalytic amount of silver
tetrafluoroborate at room temperature under nitrogen. The
reaction mixture was allowed to stir at room temperature for
15 min, upon which the starting material was consumed as
monitored by TLC. The reaction mixture was quickly passed
through a small amount of Florisil using a 1:1 mixture of
hexanes/ethyl acetate, and the solvent was removed in vacuo
to provide 31 as a pale yellow oil (0.059 g, 98%): TLC Rf 0.46
1
acetate); IR (neat) ν 2953, 1742, 1726, 1435 cm-1; H NMR δ

618 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
7.70 (dd, 1H, J ) 7.5, 1.5 Hz), 7.39 (dd, 1H, J ) 7.5, 1.5 Hz),
7.24-7.37 (m, 2H), 7.00 (dt, 1H, J ) 15.6, 6.5 Hz), 6.82 (t, 1H,
J ) 1.8 Hz), 5.92 (dt, 1H, J ) 15.6, 1.5 Hz), 4.37 (d, 2H, J )
1.8 Hz), 3.71 (s, 3H), 2.49-2.59 (m, 4H), 2.07 (s, 3H), 0.081 (s,
9H), 0.23 (s, 3H), 0.22 (s, 3H); 13C NMR δ 169.6, 165.1, 147.0,
138.2, 132.4, 128.9, 128.3, 128.0, 123.0, 122.2, 94.3, 86.2, 81.1,
78.5, 64.0, 52.0, 51.7, 31.4, 26.0, 21.1, 18.7, 18.5, -1.1; HMRS
(EI) calcd for C26H34O5Si (M+ - C4H9) 397.1471, found 397.1462.
7-[2-[1-Acetoxy-4-((tert-butyldimethylsilyl)oxy))-2-butynyl]-
phenyl]hept-2-en-6-ynoate (0.132 g, 0.32 mmol) was placed in
a nitrogen-flushed, oven-dried flask and dissolved in methanol
(15 mL). A catalytic amount of potassium carbonate (≈5 mg)
was then added under rapid stirring. After 2.5 h the reaction
mixture was filtered and concentrated. The residue was
purified by silica gel chromatography (3:1 hexanes/ethyl
acetate) to give alcohol 35 (0.049 g, 87%) as a yellow oil: TLC
Rf 0.54 (2:1 hexanes/ethyl acetate); IR (neat) ν 3435, 2953,
P r ep a r a tion of (4-((ter t-Bu tyld im eth ylsilyl)oxy)-1-(2-
eth yn ylph en yl)-1,2-bu tadien -3-yl)diph en ylph osph in e Ox-
id e (38). Compound 34 (0.047 g, 0.57 mmol) was transferred
to an oven-dried, nitrogen-flushed flask and diluted in THF
(3 mL) and triethylamine (0.076 mL, 0.047 g, 0.47 mmol). The
resulting solution was cooled to -78 °C in a dry ice-acetone
bath. Chlorodiphenylphosphine (0.019 mL, 0.035 g, 0.16
mmol) was added via syringe in a dropwise fashion to a
vigorously stirred reaction mixture. After 2 h, the reaction
mixture was concentrated at 0 °C and immediately subjected
to chromatography on deactivated silica gel (70:29:1 hexanes/
ethyl acetate/triethylamine) to yield the unstable allene 38
(0.050 g, 98%) as a light yellow oil: TLC Rf 0.07 (3:1 hexanes/
1
ethyl acetate); H NMR δ 7.73-7.87 (m, 4H), 7.30-7.56 (m,
7H), 7.16-7.25 (m, 3H), 6.87-6.94 (dt, 1H, J ) 10.5, 2.9 Hz),
4.60-4.65 (m, 2H), 3.29 (s, 1H), 0.82 (s, 9H), 0.01 (s, 3H), 0.00
(s, 3H); unstability of this compound precluded any attempts
at further characterization.
1
1724, 1660, 1080 cm-1; H NMR δ 7.57 (dd, 1H, J ) 7.2, 1.4
Hz), 7.31 (dd, 1H, J ) 7.2, 1.4 Hz), 7.13-7.26 (m, 2H), 6.98
(dt, 1H, J ) 15.6, 5.4 Hz), 5.88 (dt, 1H, J ) 15.6, 1.5 Hz), 5.78
(dt, 1H, J ) 5.4, 1.8 Hz), 4.30 (d, 2H, J ) 1.8 Hz), 3.66 (s, 3H),
2.75 (d, 1H, J ) 5.4 Hz), 2.54 (t, 2H, J ) 2.5 Hz), 2.44 (q, 2H,
J ) 2.5 Hz), 0.79 (s, 9H), 0.00 (s, 6H); 13C NMR δ 169.1, 147.1,
142.0, 132.5, 128.5, 128.3, 126.9, 122.4, 121.9, 93.8, 85.2, 84.2,
79.4, 63.1, 52.0, 51.9, 31.3, 25.9, 18.9, 18.5, -1.1; HMRS (EI)
calcd for C24H32O4Si (M+) 355.1366, found 355.1366.
F or m a t ion of (2-((ter t-Bu t yld im et h ylsilyl)oxy)-1-(2-
n aph th yl)eth yl)diph en ylph osph in e Oxide (40) via En yn e
Allen e Cycliza tion of En yn e Allen e 38. Compound 38
(0.050 g, 0.10 mmol) was dissolved in chlorobenzene (6.5 mL)
and transferred to a pressure tube. Nitrogen was passed
through the resulting solution for 10 min, after which 1,4-CHD
(1.5 mL, 1.3 g, 16 mmol) was added. The pressure tube was
then capped and immersed into a 37 °C oil bath for 3.5 h. The
reaction mixture was concentrated, and the resulting residue
was purified by silica gel chromatography (3:2 hexanes/ethyl
acetate) to give the cyclized product 40 as a colorless crystalline
solid (0.035 g, 70%): TLC Rf 0.40 (3:2 hexanes/ethyl acetate);
IR (neat) ν 2894, 1429, 1160, 1094 cm-1; 1H NMR δ 7.92-7.99
(m, 1H), 7.63-7.80 (m, 5H) 7.35-7.54 (m, 7H), 7.10-7.24 (m,
4H), 4.19-4.36 (m, 2H), 3.90 (dt, 1H, J ) 8.1, 5.1 Hz), 0.64 (s,
9H), -0.26 (s, 3H), -0.33 (s, 3H); 13C NMR δ 125.7-131.8
(aromatic), 63.9 (d, 1C, 2J PC ) 3.3 Hz), 50.5 (d, 1C, 1J PC ) 65.8
Hz), 25.9, 22.9, -1.7; 31P NMR δ 30.6; HMRS (EI) calcd for
C30H35SiPO2 (M+ - C4H9) 429.1440, found 429.1450.
P r ep a r a tion of 3-(2-Eth yn ylp h en yl)-2-p r op yn -1-ol (36).
3-(2-Iodophenyl)-2-propyn-1-ol (8) (1.200 g, 4.65 mmol) was
subjected to coupling conditions similar to those for the
preparation of 8 using triethylamine (1.944 mL, 1.411 g, 13.95
mmol), bis(triphenylphosphine)palladium (II) chloride (0.098
g, 0.14 mmol), copper(I) iodide (0.089 g, 0.47 mmol), and
(trimethylsilyl)acetylene (0.986 mL, 0.685 g, 6.98 mmol) and
stirring for 15 min at room temperature. Radial chromatog-
raphy with an 85:15 mixture of hexanes/diethyl ether gave
1.053 g (99%) of 3-[2-[(trimethylsilyl)ethynyl]phenyl]-2-propyn-
1-ol as a pale yellow oil: TLC Rf 0.37 (3:1 hexanes/ethyl
acetate); IR (neat) ν 3385 (br), 3063, 2961, 2899, 2866, 2234,
P r ep a r a tion of Meth yl 7-[2-(4-((ter t-bu tyld im eth ylsi-
lyl)oxy)-3-(d ip h en ylp h osp h in yl)-2-b u t a d ien yl)p h en yl]-
h ep -2-en -6-yn oa te (41). This compound was prepared in a
manner similar to that of 38 using alcohol 35 (0.048 g, 0.13
mmol), THF (3 mL) chlorodiphenylphosphine (0.02 mL, 0.03
g, 0.1 mmol), and triethylamine (0.06 mL, 0.04 g, 0.4 mmol)
with rapid stirring for 1.5 h. Purification on deactiviated silica
gel (70:29:1 hexanes/ethyl acetate/triethylamine) gave allene
41 (0.077 g, 99%) as a yellow oil: TLC Rf 0.12 (3:2 hexanes/
1
2160 cm-1; H NMR δ 0.25 (9H, s), 1.96 (1H, t, J ) 6.1 Hz),
4.51 (2H, d, J ) 6.1 Hz), 7.20-7.25 (2H, m), 7.38-7.45 (2H,
m); 13C NMR δ 132.0, 131.7, 128.2, 128.1, 125.6, 125.4, 103.3,
98.7, 91.3, 84.2, 51.6, -0.1. Anal. Calcd for C14H16OSi: C,
73.63; H, 7.06. Found: C, 73.38; H, 7.06.
3-[2-[(Trimethylsilyl)ethynyl]phenyl]-2-propyn-1-ol (0.850 g,
3.72 mmol) was subjected to the same desilylation conditions
as 35 using potassium carbonate (≈5 mg) dissolved in 10 mL
of methanol with stirring for 45 min. The solvent was then
removed in vacuo and the residue passed through a short silica
gel column with diethyl ether. The crude product was purified
by radial chromatography with a 70:30 mixture of hexanes/
diethyl ether to yield 0.564 g (97%) of 36 as a colorless
crystalline solid: TLC Rf 0.20 (3:1 hexanes/ethyl acetate); IR
(Nujol) ν 3273 (br), 2955, 2926, 2857, 2230, 2104 cm-1; 1H NMR
δ 2.11 (1H, t, J ) 5.7 Hz), 3.27 (1H, s), 4.48 (1H, d, J ) 5.7
Hz), 7.21 (2H, m), 7.36-7.44 (2H, m); 13C NMR δ 132.6, 132.1,
128.5, 128.2, 125.4, 124.4, 91.3, 83.9, 82.0, 81.1, 51.6. Anal.
Calcd for C11H8O: C, 84.59; H, 5.16. Found: C, 84.70; H, 5.30.
P r ep a r a tion of Meth yl 2-(3-Hyd r oxy-1-p r op yn ylp h en -
yl)h ep t-2-en -6-yn oa te (37). Methyl 7-(2-iodophenyl)hept-2-
en-6-ynoate (11) (0.300 g, 0.88 mmol) was transferred to a
nitrogen-flushed, oven-dried flask and dissolved in triethyl-
amine (6 mL). Tetrakis(triphenylphosphine)palladium(0) (0.021
g, 0.02 mmol) and copper(I) bromide (0.008 g, 0.03 mmol) were
added under rapid stirring. After 10 min, propargyl alcohol
(0.08 mL, 0.07 g, 1 mmol) was added via syringe and the
resulting reaction mixture was heated to 50 °C for 1.5 h. The
reaction mixture was then filtered and concentrated. The
resulting residue was purified by silica gel chromatography
(80:20 hexanes/ethyl acetate) to afford alcohol 37 (0.175 g, 74%)
as a slightly yellow oil: TLC Rf 0.20 (3:1 hexanes/ethyl
ethyl acetate); IR (neat) ν 3405, 1925, 1724, 1485 cm-1 1H
;
NMR δ 7.83-8.04 (m, 4H), 7.36-7.71 (m, 8H), 7.10-7.28 (m,
3H), 6.87 (dt, 1H, J ) 10.8, 3Hz), 6.05 (dt, 1H, J ) 15.6, 1.5Hz),
4.69-4.73 (m, 2H), 3.87 (s, 3H), 2.58-2.73 (m, 4H), 0.91 (s,
9H), 0.09 (s, 3H), 0.08 (s, 3H); 13C NMR δ 210.5, 166.8, 147.0,
1
126.8-133.9 (aromatic), 122.3, 103.8 (d, 1C, J PC ) 98.3 Hz),
2
96.6 (d, 1C,
10.8 Hz), 51.7, 31.6, 25.9, 18.8, 18.5, -1.4;
3J PC ) 13.0 Hz), 93.5, 79.6, 60.7 (d, 1C, J PC
)
31P NMR δ 27.9;
HMRS (EI) calcd for C36H41SiPO4 (M+) 596.2512, found
596.2516.
P r ep a r a tion of Meth yl 1H-4-Vin yl-1,2-d ih yd r oben z[e]-
in d en e-1-a ceta te (43) via Ta n d em En yn e Allen e-Ra d ica l
Cycliza tion of En yn e Allen e 41. This reaction was similar
to the thermolysis of 38 using enyne allene 41 (0.077 g, 0.13
mmol). The pressure tube was immersed in a 75 °C oil bath
for 8 h, after which it was concentrated affording a yellow oil
which proved to be unstable when subjected to silica gel
chromatography. The residue was dissolved in THF (5 mL)
and transferred to an oven-dried, nitrogen-flushed flask. To
this rapidly stirred mixture was added a solution of tetra-n-
butylammonium fluoride in THF (0.13 mL, 1 M, 0.13 mmol).
After 1 h, the reaction mixture was concentrated and subjected
to chromatography (9:1 hexanes/ethyl acetate) to afford dihy-
drobenz[e]indene 43 as a light yellow oil (0.024 g, 70%): TLC
Rf 0.82 (3:2 hexanes/ethyl acetate); IR (neat) ν 2952, 1737,
1
acetate); IR (neat) ν 3465, 1724, 1664, 1227 cm-1; H NMR δ
1
7.63 (dd, 1H, J ) 7.8, 1.5 Hz), 7.20-7.33 (m, 3H), 7.04 (dt,
1H, J ) 15.6, 5.4 Hz), 5.92 (d, 1H, J ) 15.6 Hz), 4.53 (s, 2H),
3.70 (s, 3H), 2.87 (s, 1H), 2.60 (t, 2H, J ) 5.4 Hz), 2.44 (q, 2H,
J ) 5.4 Hz); 13C NMR δ 166.7, 147.0, 139.0, 132.9, 129.3, 128.1,
123.1, 101.3, 100.8, 93.0, 84.3, 77.5, 77.1, 60.8, 31.7, 30.3, 19.2.
1435, 1259 cm-1; H NMR δ 7.84 (m, 3H), 7.47 (td, 1H, J )
6.6, 1.2 Hz), 7.41 (t, 1H, J ) 6.6 Hz), 6.92 (dd, 1H, J ) 17.7,
11.1 Hz), 5.83 (dd, 1H, J ) 17.7 1.2 Hz), 5.37 (dd, 1H, J )
11.1, 1.2 Hz), 4.14 (ddd, 1H, J ) 9.3, 8.1, 3 Hz), 3.73 (s, 3H),
3.10-3.19 (m, 2H), 2.79 (dd, 1H, J ) 15.6, 3 Hz), 2.33-2.43

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 619
(m, 2H), 2.15 (dd, 1H, J ) 14.1, 6.0 Hz); 13C NMR δ 173.4,
141.5, 139.4, 135.3, 133.4, 133.0, 129.4, 129.0, 126.3, 125.3,
124.2, 123.7, 115.9, 51.9, 40.6, 38.8, 31.0, 30.6; HMRS (EI)
calcd for C18H18O2 (M+) 266.1307, found 266.1301.
pale yellow oil (0.322 g, 80%): TLC Rf 0.19 (2:1 hexanes/ethyl
acetate); IR (neat) ν 3460, 2951, 2212, 1711, 1651, 1277 cm-1
;
1H NMR δ 6.85 (tq, J ) 6.9, 1.5 Hz, 1H), 5.75-5.72 (m, 2H),
4.38 (d, J ) 0.6 Hz, 2H), 3.69 (s, 3H), 2.98 (s, 1H), 2.53-2.34
(m, 4H), 1.80 (m, 3H); 13C NMR δ 168.8, 140.4, 128.6, 120.0,
118.2, 97.0, 94.8, 82.2, 78.7, 51.8, 51.2, 27.5, 18.9, 12.4; HRMS
(EI) calcd for C14H16O3 (M+) 232.1100, found 232.1101.
The (Z,Z) compound 53 was prepared like 51 using methyl
(Z,Z)-2-methyl-12-((tert-butyldimethylsilyl)oxy)dodeca-2,8-di-
ene-6,10-diynoate (0.100 g, 0.289 mmol), dichloromethane (8
mL), and boron trifluoride diethyl etherate (0.107 mL, 0.870
mmol) with stirring for 1 h. Purification afforded 53 as a pale
yellow oil (0.055 g, 82%): TLC Rf 0.20 (2:1 hexanes/ethyl
P r ep a r a tion of [1-[2-(6-(Meth oxyca r bon yl)h ex-5-en -1-
yn yl)p h en yl]p r op a d ien -1-yl]d ip h en ylp h osp h in e Oxid e
(44). This compound was prepared in a manner similar to
that of 38 using enediyne alcohol 37 (0.150 g, 0.56 mmol), THF
(10 mL) chlorodiphenylphosphine (0.12 mL, 0.15 g, 0.7 mmol),
and triethylamine (0.27 mL, 0.2 g, 1.7 mmol) with rapid
stirring for 3 h. The reaction mixture was concentrated and
subjected to silica gel chromatography (60:39:1 hexanes/ethyl
acetate/triethylamine). Purification afforded allene 44 (0.245
g, 97%) as a light yellow oil: TLC Rf 0.05 (2:1 hexanes/ethyl
acetate); IR (neat) ν 3443, 2951, 2212, 1711, 1645, 1217 cm-1
;
1
acetate); IR (neat) ν 1720, 1437, 1192 cm-1; H NMR δ 8.22
1H NMR δ 6.02 (tq, J ) 6.9, 1.5 Hz, 1H), 5.78-5.75 (m, 2H),
4.42 (d, J ) 1.5 Hz, 2H), 3.70 (s, 3H), 2.77-2.67 (m, 2H), 2.50-
2.44 (m, 2H), 2.30 (s, 1H), 1.89 (m, 3H); 13C NMR δ 168.3,
141.2, 128.1, 120.5, 117.9, 98.0, 94.4, 82.8, 78.5, 51.5, 51.4, 28.7,
20.5, 19.7; HRMS (EI) calcd for C14H16O3 (M+) 232.1100, found
232.1110.
(m, 1H), 7.70-7.82 (m, 4H), 7.26-7.49 (m, 7H), 7.02-7.19 (m,
3H), 5.97 (d, 1H, J ) 14.4 Hz), 4.79 (d, 2H, J ) 10.8 Hz), 3.70
(s, 3H) 2.63 (t, 2H, J ) 5.4 Hz) 2.51 (q, 2H, J ) 5.4 Hz); 31P
NMR δ 31.9.
P r ep a r a tion of Meth yl (E,Z)-12-Hyd r oxyd od eca -2,8-
d ien e-6,10-d iyn oa te (51). To a stirred solution of methyl
(E,Z)-12-((tert-butyldimethylsilyl)oxy)dodeca-2,8-diene-6,10-
diynoate7c (0.700 g, 2.11 mmol) in dichloromethane (30 mL)
was added boron trifluoride diethyl etherate (0.775 mL, 6.30
mmol) via syringe. After being stirred at room temperature
under nitrogen for 30 min, the reaction mixture was quenched
with water and extracted with dichloromethane (2 × 40 mL).
The combined organic layers were dried over anhydrous
magnesium sulfate, filtered, and evaporated. Purification by
radial chromatography (3:1 hexanes/ethyl acetate) afforded 51
as a yellow oil (0.396 g, 86%): TLC Rf 0.18 (2:1 hexanes/ethyl
P r ep a r a tion of (Z,E)-12-Acetoxyd od eca -4,10-d ien e-2,6-
d iyn -1-ol (54). To a stirred solution of methyl (E,Z)-12-((tert-
butyldimethylsilyl)oxy)dodeca-2,8-diene-6,10-diynoate7c (1.00
g, 3.01 mmol) in dichloromethane (15 mL) at 0 °C was added
diisobutylaluminum hydride (1.5 M solution in toluene, 4.00
mL, 6.00 mmol) via syringe. After being stirred at 0 °C under
nitrogen for 20 min, the reaction mixture was quenched with
potassium fluoride monohydrate (0.560 g, 5.95 mmol) and
excess water followed by a dichloromethane/water extraction.
The combined organic layers were dried over anhydrous
magnesium sulfate, filtered, and concentrated in vacuo. The
resulting yellow residue was subjected to radial chromatog-
raphy (9:1 hexanes/ethyl acetate) to afford (E,Z)-12-((tert-
butyldimethylsilyl)oxy)dodeca-2,8-diene-6,10-diyn-1-ol as a light
yellow oil (0.715 g, 78%): TLC Rf 0.31 (2:1 hexanes/ethyl
acetate); IR (neat) ν 3379, 2930, 2212, 1672, 1579, 1255, 1076
cm-1; 1H NMR δ 5.81-5.63 (m, 4H), 4.47 (d, J ) 1.2 Hz, 2H),
4.09-4.05 (m, 2H), 2.48-2.40 (m, 2H), 2.32-2.23 (m, 2H), 1.79
(bs, 1H), 0.88 (s, 9H), 0.11 (s, 6H); 13C NMR δ 130.5, 130.4,
120.1, 118.0, 97.6, 94.6, 82.2, 78.5, 63.4, 52.3, 31.2, 25.8, 19.8,
18.3, -5.2; HRMS (EI) calcd for C18H28SiO2 (M+) 304.1859,
found 304.1866.
acetate); IR (neat) ν 3435, 2212, 1721, 1659, 1287 cm-1 1H
;
NMR δ 7.08 (dt, J ) 15.6, 6.6 Hz, 1H), 5.90 (dt, J ) 15.6, 1.5
Hz, 1H), 5.76-5.73 (m, 2H), 4.40 (d, J ) 1.2 Hz, 2H), 3.69 (s,
3H), 3.12 (bs, 1H), 2.56-2.37 (m, 4H); 13C NMR δ 167.3, 147.4,
121.9, 119.8, 118.4, 96.3, 95.0, 82.2, 79.2, 51.6, 51.2, 30.9, 18.7;
HRMS (EI) calcd for C13H14O3 (M+) 218.0943, found 218.0923.
P r ep a r a t ion of Met h yl (E,Z)- a n d (Z,Z)-2-Met h yl-12-
h yd r oxyd od eca -2,8-d ien e-6,10-d iyn oa te (52 a n d 53). (Z)-
10-((tert-Butyldimethylsilyl)oxy)dec-6-ene-4,8-diynal (50)7c (0.150
g, 0.543 mmol) was subjected to Horner-Emmons reaction
conditions similar to those for the preparation of 11 using
trimethyl 2-methylphosphonoacetate (0.160 g, 0.816 mmol),
acetonitrile (4 mL), lithium chloride (0.046 g, 1.09 mmol), and
DBU (0.122 mL, 0.816 mmol). The reaction mixture was
stirred at rt for 10 min, quenched with water, and extracted
with diethyl ether (3 × 40 mL). The combined organic layers
were dried over anhydrous magnesium sulfate, filtered, and
concentrated in vacuo. Purification of the product was achieved
by radial chromatography (98:2 hexanes/ethyl acetate) to
afford methyl (E,Z)-2-methyl-12-((tert-butyldimethylsilyl)oxy)-
dodeca-2,8-diene-6,10-diynoate and methyl (Z,Z)-2-methyl-12-
((tert-butyldimethylsilyl)oxy)dodeca-2,8-diene-6,10-diynoate in
an 8:1 ratio as yellow oils. Methyl (E,Z)-2-methyl-12-((tert-
butyldimethylsilyl)oxy)dodeca-2,8-diene-6,10-diynoate (0.138
g, 73%): TLC Rf 0.64 (2:1 hexanes/ethyl acetate); IR (neat) ν
(E,Z)-12-((tert-Butyldimethylsilyl)oxy)dodeca-2,8-diene-6,10-
diyn-1-ol (0.700 g, 2.30 mmol) was dissolved in dichlo-
romethane (15 mL); then triethylamine (1.60 mL, 11.5 mmol)
and acetic anhydride (0.434 mL, 4.60 mmol) were added via
syringe. After being stirred at room temperature overnight,
the reaction mixture was diluted with water and extracted
with dichloromethane (3 × 50 mL). The combined organic
layers were dried over anhydrous magnesium sulfate, filtered,
and concentrated in vacuo to give a yellow residue. Purifica-
tion was achieved by radial chromatography (95:5 hexanes/
ethyl acetate) to yield (E,Z)-1-acetoxy-12-((tert-butyldimeth-
ylsilyl)oxy)dodeca-2,8-diene-6,10-diyne as a pale yellow oil
(0.758 g, 95%): TLC Rf 0.56 (2:1 hexanes/ethyl acetate); IR
1
(neat) ν 2930, 2216, 1742, 1232, 1076 cm-1; H NMR δ 5.87-
1
2953, 2214, 1716, 1653, 1265 cm-1; H NMR δ 6.79-6.72 (m,
5.76 (m, 1H), 5.75-5.73 (m, 2H), 5.67-5.56 (m, 1H), 4.49 (dd,
J ) 6.3, 1.2 Hz, 2H), 4.47 (d, J ) 1.2 Hz, 2H), 2.47-2.40 (m,
2H), 2.33-2.23 (m, 2H), 2.02 (s, 3H), 0.88 (s, 9H), 0.10 (s, 6H);
13C NMR δ 170.7, 133.9, 125.2, 119.9, 118.1, 97.3, 94.8, 82.1,
78.6, 64.9, 52.2, 31.3, 25.8, 20.9, 19.6, 18.2, -5.2; HRMS (EI)
calcd for C20H30SiO3 (M+) 346.1965, found 346.1945.
1H), 5.76-5.74 (m, 2H), 4.47 (d, J ) 0.9 Hz, 2H), 3.71 (s, 3H),
2.53-2.36 (m, 4H), 1.84-1.82 (m, 3H), 0.88 (s, 9H), 0.11 (s,
6H); 13C NMR δ 139.8, 128.9, 127.4, 119.8, 118.3, 96.9, 94.9,
82.1, 78.6, 52.2, 51.7, 27.9, 25.8, 19.1, 18.2, 12.5, -5.2; HRMS
(EI) calcd for C20H30SiO3 (M+) 346.1964, found 346.1965.
Methyl (Z,Z)-2-methyl-12-((tert-butyldimethylsilyl)oxy)dodeca-
2,8-diene-6,10-diynoate (0.017 g, 9%): TLC Rf 0.66 (2:1 hex-
anes/ethyl acetate); IR (neat) ν 2953, 2212, 1719, 1649, 1254
cm-1; 1H NMR δ 6.04 (tq, J ) 6.9, 1.5 Hz, 1H), 5.77-5.74 (m,
2H), 4.47 (d, J ) 1.5 Hz, 2H), 3.70 (s, 3H), 2.74-2.64 (m, 2H),
To a stirred solution of (E,Z)-1-acetoxy-12-((tert-butyldimeth-
ylsilyl)oxy)dodeca-2,8-diene-6,10-diyne (0.600 g, 1.73 mmol) in
THF (10 mL) was added tetra-n-butylammonium fluoride (1.0
M solution in THF, 5.00 mL, 5.00 mmol) at room temperature
under nitrogen. After the reaction mixture was stirred for 2
min, it was quenched with water and extracted with diethyl
ether (2 × 50 mL). The combined organic layers were dried
over anhydrous magnesium sulfate, filtered, and evaporated.
Purification by radial chromatography (3:1 hexanes/ethyl
acetate) afforded 54 as a light yellow oil (0.335 g, 83%): TLC
Rf 0.15 (2:1 hexanes/ethyl acetate); IR (neat) ν 3435, 2936,
2.49-2.43 (m, 2H), 1.89 (m, 3H), 0.88 (s, 9H), 0.11 (s, 6H); 13
C
NMR δ 168.1, 141.0, 128.1, 120.0, 118.0, 97.5, 94.8, 82.1, 78.6,
52.3, 51.3, 28.6, 25.8, 20.6, 19.8, 18.3, -5.1; HRMS (EI) calcd
for C20H30SiO3 (M+) 346.1964, found 346.1945.
The (E,Z) compound 52 was prepared like 51 using methyl
(E,Z)-2-methyl-12-((tert-butyldimethylsilyl)oxy)dodeca-2,8-di-
ene-6,10-diynoate (0.600 g, 1.73 mmol), dichloromethane (15
mL), and boron trifluoride diethyl etherate (0.640 mL, 5.20
mmol) with stirring for 40 min. Purification afforded 52 as a
1
2212, 1738, 1240, 1024 cm-1; H NMR δ 5.86-5.75 (m, 1H),
5.74-5.71 (m, 2H), 5.65-5.54 (m, 1H), 4.47 (dd, J ) 6.3, 1.2
Hz, 2H), 4.38 (d, J ) 1.5 Hz, 2H), 2.77 (bs, 1H), 2.46-2.39 (m,

620 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
2H), 2.30-2.21 (m, 2H), 2.00 (s, 3H); 13C NMR δ 171.0, 133.9,
125.1, 120.2, 117.8, 97.6, 94.4, 82.5, 78.5, 64.9, 51.2, 31.1, 20.9,
19.4; HRMS (EI) calcd for C14H16O3 (M+) 232.1099, found
232.1120.
(Z)-10-((tert-Butyldimethylsilyl)oxy)-N-(phenylmethoxy)dec-
6-ene-4,8-diyn-1-imine (0.360 g, 0.940 mmol) was subjected to
desilylation reaction conditions similar to those for the prepa-
ration of 54 using tetra-n-butylammonium fluoride (1.0 M
solution in THF, 2.82 mL, 2.82 mmol). Purification by radial
chromatography (3:1 hexanes/ethyl acetate) afforded 56 as a
pale yellow oil (0.203 g, 1:1 mixture of E/Z imine isomers,
81%): TLC Rf 0.12 (3:1 hexanes/ethyl acetate); IR (neat) ν
P r ep a r a tion of (Z,E)- a n d (Z,Z)-11-Meth oxyu n d eca -4,-
10-d ien e-2,6-d iyn -1-ol (55). To a stirred solution of (meth-
oxymethyl)triphenylphosphonium chloride (0.771 g, 2.25 mmol)
in THF (20 mL) at -78 °C under nitrogen was added
potassium tert-butoxide (0.252 g, 2.25 mmol). After being
warmed to room temperature and stirred for 1 h, the reaction
mixture was cooled to -78° C and (Z)-10-((tert-butyldimeth-
ylsilyl)oxy)dec-6-ene-4,8-diynal (50)7c (0.250 g, 0.906 mmol),
dissolved in THF (5 mL), was added dropwise via syringe.
After the mixture was stirred at -78° C for 10 min, it was
quenched with water and extracted with diethyl ether (3 ×
40 mL). The combined organic layers were dried over anhy-
drous magnesium sulfate, filtered, and concentrated in vacuo.
The residue was purified by radial chromatography (95:5
hexanes/ethyl acetate) to afford a mixture of (E,Z)- and (Z,Z)-
1-methoxy-11-((tert-butyldimethylsilyl)oxy)undeca-1,7-diene-
5,9-diyne as a pale yellow oil (0.171 g, 6:1 mixture of E:Z
isomers, 62% combined yield): TLC Rf 0.64 (2:1 hexanes/ethyl
1
3406, 2924, 2214, 1635, 1020, 748 cm-1; H NMR E isomer δ
7.66 (t, J ) 6.0 Hz, 1H), 7.37-7.25 (m, 5H), 5.80-5.76 (m, 2H),
5.07 (s, 2H), 4.31 (d, J ) 1.8 Hz, 2H), 3.04 (bs, 1H), 2.66-2.41
(m, 4H); Z isomer δ 7.10 (t, J ) 4.8 Hz, 1H), 7.37-7.25 (m,
5H), 5.80-5.76 (m, 2H), 5.11 (s, 2H), 4.35 (d, J ) 1.2 Hz, 2H),
3.04 (bs, 1H), 2.66-2.41 (m, 4H); 13C NMR δ 151.2, 150.3,
137.4, 137.1, 128.4, 128.3, 128.2, 128.0, 127.9, 127.8, 120.0,
119.9, 119.1, 118.6, 96.1, 96.0, 95.2, 94.9, 82.7, 82.3, 79.9, 79.5,
75.9, 75.7, 51.2, 51.0, 28.4, 24.6, 17.5, 16.6; HRMS (EI) calcd
for C17H17NO2 (M+) 267.1259, found 267.1247.
P r ep a r a tion of (Z)-10-Hyd r oxy-N-(d ip h en yla m in o)d ec-
6-en e-4,8-d iyn -1-im in e (57). To a stirred solution of (Z)-10-
((tert-butyldimethylsilyl)oxy)dec-6-ene-4,8-diynal (50)7c (0.400
g, 1.45 mmol) in dichloromethane (10 mL) were added 1,1-
diphenylhydrazine hydrochloride (0.384 g, 1.74 mmol) and
pyridine (0.140 mL, 1.74 mmol). The reaction mixture was
allowed to stir at room temperature for 10 min, upon which
the aldehyde had been consumed as monitored by TLC. The
solvent was removed in vacuo, and the residue was filtered
through silica gel using a 3:1 mixture of hexanes/ethyl acetate.
The filtrate was evaporated, and the residue was subjected to
radial chromatography (98:2 hexanes/ethyl acetate) to afford
(Z)-10-((tert-butyldimethylsilyl)oxy)-N-(diphenylamino)dec-6-
ene-4,8-diyn-1-imine as a yellow oil (0.610 g, 95%): TLC Rf
0.72 (3:1 hexanes/ethyl acetate); IR (neat) ν 2930, 2247, 2214,
1
acetate); IR (neat) ν 2930, 2212, 1657, 1211 cm-1; H NMR E
isomer δ 6.34 (dt, J ) 12.3, 1.2 Hz, 1H), 5.80-5.69 (m, 2H),
4.76 (dt, J ) 12.3, 7.2 Hz, 1H), 4.48 (d, J ) 1.5 Hz, 2H), 3.48
(s, 3H), 2.42-2.35 (m, 2H), 2.20-2.11 (m, 2H), 0.88 (s, 9H),
0.11 (s, 6H); Z isomer δ 5.89 (dt, J ) 6.6, 1.2 Hz, 1H), 5.80-
5.69 (m, 2H), 4.49-4.46 (m, 1H), 4.48 (d, J ) 1.5 Hz, 2H), 3.55
(s, 3H), 2.42-2.35 (m, 2H), 2.33-2.23 (m, 2H), 0.88 (s, 9H),
0.11 (s, 6H); 13C NMR δ 148.1, 146.9, 120.3, 120.1, 117.8, 117.7,
104.7, 101.0, 98.0, 94.7, 82.2, 78.4, 55.8, 52.3, 27.2, 25.8, 23.2,
21.6, 20.2, 18.2, -5.2. Anal. Calcd for C18H28SiO2: C, 71.00;
H, 9.27. Found: C, 70.80; H, 9.35.
1
1591, 1495, 1211, 1072 cm-1; H NMR δ 7.39-7.31 (m, 4H),
The subsequent desilylation was carried out as described
for 54 using (E,Z)/(Z,Z)-1-methoxy-11-((tert-butyldimethylsi-
lyl)oxy)undeca-1,7-diene-5,9-diyne (0.125 g, 0.411 mmol), THF
(20 mL), and tetra-n-butylammonium fluoride (1.0 M solution
in THF) (1.23 mL, 1.23 mmol) to provide 55 as a light yellow
oil (0.069 g, 6:1 mixture of E:Z isomers, 88% combined yield):
TLC Rf 0.21 (2:1 hexanes/ethyl acetate); IR (neat) ν 3410, 2934,
2211, 1657, 1209 cm-1; 1H NMR E isomer δ 6.36 (dt, J ) 12.3,
1.2 Hz, 1H), 5.82-5.71 (m, 2H), 4.86 (dt, J ) 12.3, 7.2 Hz,
1H), 4.41 (d, J ) 2.7 Hz, 2H), 3.50 (s, 3H), 2.50-2.37 (m, 3H),
2.20-2.11 (m, 2H); Z isomer δ 5.90 (dt, J ) 6.6, 1.2 Hz, 1H),
5.82-5.71 (m, 2H), 4.50-4.43 (m, 1H), 4.41 (d, J ) 2.7 Hz,
2H), 3.56 (s, 3H), 2.50-2.37 (m, 3H), 2.34-2.25 (m, 2H); 13C
NMR δ 147.9, 146.9, 120.8, 120.5, 117.7, 117.5, 104.7, 101.5,
98.3, 94.3, 82.7, 78.6, 59.5, 56.1, 51.6, 51.5, 26.8, 23.2, 21.4,
20.2; HRMS (EI) calcd for C12H13O2 (M+ - H) 189.0916, found
189.0930.
7.15-7.05 (m, 6H), 6.56 (t, J ) 4.8 Hz, 1H), 5.76-5.74 (m, 2H),
4.47 (s, 2H), 2.68-2.61 (m, 2H), 2.57-2.48 (m, 2H), 0.90 (s,
9H), 0.13 (s, 6H); 13C NMR δ 144.0, 136.9, 129.7, 124.0, 122.3,
120.0, 118.0, 97.6, 94.8, 82.1, 78.4, 52.3, 31.8, 25.8, 18.3, 17.7,
-5.1; HRMS (EI) calcd for C28H34SiN2O (M+) 442.2440, found
442.2451.
(Z)-10-((tert-Butyldimethylsilyl)oxy)-N-(diphenylamino)dec-
6-ene-4,8-diyn-1-imine (0.550 g, 1.24 mmol) was subjected to
desilylation reaction conditions similar to those used for the
preparation of 54 using tetra-n-butylammonium fluoride (1.0
M solution in THF, 3.70 mL, 3.70 mmol). Purification by
radial chromatography (3:1 hexanes/ethyl acetate) gave 57 as
a light yellow oil (0.380 g, 93%): TLC Rf 0.18 (3:1 hexanes/
ethyl acetate); IR (neat) ν 3393, 2924, 2212, 1591, 1495, 1211,
1092 cm-1; 1H NMR δ 7.39-7.32 (m, 4H), 7.15-7.07 (m, 6H),
6.61 (t, J ) 4.8 Hz, 1H), 5.79-5.76 (m, 2H), 4.29 (d, J ) 5.1
Hz, 2H), 2.69-2.61 (m, 2H), 2.60-2.49 (m, 3H); 13C NMR δ
144.0. 138.4, 129.6, 124.0, 122.4, 120.3, 117.9, 97.7, 94.6, 82.8,
78.6, 51.3, 31.6, 17.6; HRMS (EI) calcd for C22H20N2O (M+)
328.1576, found 328.1582.
P r ep a r a tion of (Z)-10-Hyd r oxy-N-(p h en ylm eth oxy)-
d ec-6-en e-4,8-d iyn -1-im in e (56). To a stirred solution of (Z)-
10-((tert-butyldimethylsilyl)oxy)dec-6-ene-4,8-diynal (50)7c (0.320
g, 1.16 mmol) in dichloromethane (15 mL) were added O-
benzylhydroxylamine hydrochloride (0.222 g, 1.39 mmol) and
pyridine (0.112 mL, 1.39 mmol). The reaction mixture was
allowed to stir at room temperature for 30 min, upon which
the aldehyde had been consumed as monitored by TLC. The
solvent was removed in vacuo, and the residue was washed
through silica gel using a 3:1 mixture of hexanes/ethyl acetate.
The filtrate was evaporated, and the residue was subjected to
radial chromatography (98:2 hexanes/ethyl acetate) to provide
(Z)-10-((tert-butyldimethylsilyl)oxy)-N-(phenylmethoxy)dec-6-
ene-4,8-diyn-1-imine as a pale yellow oil (0.425 g, 1:1 mixture
of E/Z imine isomers, 96%): TLC Rf 0.53 (3:1 hexanes/ethyl
acetate); IR (neat) ν 2930, 2216, 1256, 1076, 837 cm-1; 1H NMR
E isomer δ 7.57 (t, J ) 6.0 Hz, 1H), 7.37-7.25 (m, 5H), 5.79-
5.75 (m, 2H), 5.05 (s, 2H), 4.50-4.48 (m, 2H), 2.66-2.40 (m,
4H), 0.90 (s, 9H), 0.12 (s, 6H); Z isomer δ 6.83 (t, J ) 4.8 Hz,
1H), 7.37-7.25 (m, 5H), 5.79-5.75 (m, 2H), 5.11 (s, 2H), 4.50-
P r ep a r a tion of (Z)-10-((ter t-Bu tyld im eth ylsilyl)oxy)-
u n d ec-6-en e-4,8-d iyn a l (58). To a stirred solution of (Z)-7-
chlorohept-6-en-4-yn-1-ol7c (1.90 g, 13.1 mmol) and n-butyl-
amine (2.20 mL, 22.3 mmol) in anhydrous benzene (25 mL)
was added tetrakis(triphenylphosphine)palladium(0) (0.258 g,
0.223 mmol) under nitrogen. After the reaction mixture was
stirred at room temperature for 10 min, copper(I) iodide (0.100
g, 0.525 mmol) was added and the resulting mixture was
stirred for an additional 10 min. 3-((tert-Butyldimethylsilyl)-
oxy)-1-butyne (2.90 g, 15.8 mmol) was then added, and the
reaction mixture was allowed to stir at 50 °C under nitrogen
for 24 h. The solvent was removed in vacuo and the residue
filtered through silica gel using a 2:1 mixture of hexanes/ethyl
acetate. The filtrate was evaporated and the residue subjected
to radial chromatography (9:1 hexanes/ethyl acetate) to yield
(Z)-10-((tert-butyldimethylsilyl)oxy)undec-6-ene-4,8-diyn-1-ol
as a pale yellow oil (3.04 g, 79%): TLC Rf 0.32 (2:1 hexanes/
4.48 (m, 2H), 2.66-2.40 (m, 4H), 0.90 (s, 9H), 0.12 (s, 6H); 13
C
NMR δ 150.1, 149.4, 137.8, 137.5, 128.3, 128.2, 127.9, 127.8,
127.7, 127.6, 119.7, 119.6, 118.6, 118.5, 96.3, 96.1, 95.1, 95.0,
82.1, 82.0, 79.1, 79.0, 75.8, 75.6, 52.3, 52.2, 28.7, 25.8, 25.0,
18.3, 17.6, 16.8, -5.1; HRMS (EI) calcd for C19H22NSiO2 (M+
- C4H9) 324.1420, found 324.1436.
ethyl acetate); IR (neat) ν 3364, 2953, 2212, 1256, 1099 cm-1
;
1H NMR δ 5.74-5.72 (m, 2H), 4.67 (dq, J ) 0.6, 6.6 Hz, 1H),
3.77 (t, J ) 6.6 Hz, 2H), 2.47 (dt, J ) 0.9, 6.6 Hz, 2H), 2.11
(bs, 1H), 1.76 (quintet, J ) 6.6 Hz, 2H), 1.43 (d, J ) 6.6 Hz,
3H), 0.87 (s, 9H), 0.11 (s, 3H), 0.10 (s, 3H); 13C NMR δ 119.9,

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 621
118.3, 98.5, 97.5, 80.8, 78.7, 61.2, 59.6, 31.0, 25.8, 25.3, 18.2,
16.2, -4.6, -5.1; HRMS (EI) calcd for C13H19SiO2 (M+ - C4H9)
235.1154, found 235.1148.
0.35 (2:1 hexanes/ethyl acetate); IR (neat) ν 3356, 2932, 2214,
1
1256, 1076, 837 cm-1; H NMR δ 5.76-5.73 (m, 2H), 4.47 (d,
J ) 1.8 Hz, 2H), 3.64 (t, J ) 6.3 Hz, 2H), 2.40 (dt, J ) 1.8, 6.6
Hz, 2H), 1.89 (s, 1H), 1.77-1.54 (m, 4H), 0.88 (s, 9H), 0.11 (s,
6H); 13C NMR δ 120.4, 117.9, 98.2, 94.5, 82.3, 78.5, 62.3, 52.3,
Pyridinium chlorochromate (2.48 g, 11.5 mmol) was added
to a stirred solution of (Z)-10-((tert-butyldimethylsilyl)oxy)-
undec-6-ene-4,8-diyn-1-ol (2.80 g, 9.60 mmol) in dichlo-
romethane (50 mL). The resulting reaction mixture was
allowed to stir at room temperature for 24 h, upon which the
alcohol had been consumed as monitored by TLC. The solvent
was removed in vacuo and the residue filtered through silica
gel using a 2:1 mixture of hexanes/ethyl acetate. The filtrate
was evaporated and the residue subjected to radial chroma-
tography (95:5 hexanes/ethyl acetate) to afford 58 as a colorless
oil (2.15 g, 77%): TLC Rf 0.54 (2:1 hexanes/ethyl acetate); IR
(neat) ν 2955, 2216, 1728, 1256, 1099 cm-1; 1H NMR δ 9.78 (t,
J ) 0.9 Hz, 1H), 5.74-5.70 (m, 2H), 4.67 (dq, J ) 1.2, 6.6 Hz,
1H), 2.69-2.65 (m, 4H), 1.42 (d, J ) 6.6 Hz, 3H), 0.87 (s, 9H),
0.11 (s, 3H), 0.10 (s, 3H); 13C NMR δ 200.2, 119.3, 118.8, 99.0,
95.5, 80.5, 78.9, 59.4, 42.4, 25.7, 25.3, 18.2, 13.0, -4.6, -5.0;
HRMS (EI) calcd for C13H17SiO2 (M+ - C4H9) 233.0998, found
233.0998.
31.8, 25.8, 24.7, 19.5, 18.3, -5.2; HRMS (EI) calcd for C17H28
-
SiO2 (M+) 292.1859, found 292.1852.
(Z)-11-((tert-Butyldimethylsilyl)oxy)undec-7-ene-5,9-diyn-
1-ol (1.00 g, 3.42 mmol) was subjected to PCC oxidation
reaction conditions similar to those used for the preparation
of 58 using pyridinium chlorochromate (1.10 g, 5.10 mmol).
Purification by radial chromatography (95:5 hexanes/ethyl
acetate) furnished 60 as a pale yellow oil (0.845 g, 85%): TLC
Rf 0.58 (2:1 hexanes/ethyl acetate); IR (neat) ν 2932, 2214,
1726, 1256, 1076, 837 cm-1 1H NMR δ 9.78 (t, J ) 1.5 Hz,
;
1H), 5.76-5.73 (m, 2H), 4.46 (d, J ) 0.9 Hz, 2H), 2.61 (dt, J )
1.5, 7.2 Hz, 2H), 2.44 (dt, J ) 0.6, 7.2 Hz, 2H), 1.85 (quintet,
J ) 7.2 Hz, 2H), 0.87 (s, 9H), 0.10 (s, 6H); 13C NMR δ 201.7,
119.8, 118.3, 96.8, 94.8, 82.1, 79.1, 52.2, 42.6, 25.8, 20.9, 19.1,
18.2, -5.2; HRMS (EI) calcd for C17H26SiO2 (M+) 290.1702,
found 290.1693.
P r ep a r a tion of Meth yl (E,Z)-12-Hyd r oxytr id eca -2,8-
d ien e-6,10-d iyn oa te (59). Aldehyde 58 (0.450 g, 1.55 mmol)-
was subjected to Horner-Emmons reaction conditions similar
to those for the preparation of 11 and 52 using trimethyl
phosphonoacetate (0.422 g, 2.32 mmol), acetonitrile (10 mL),
lithium chloride (0.131 g, 3.10 mmol), and DBU (0.347 mL,
2.32 mmol). Purification afforded methyl (E,Z)-12-((tert-bu-
tyldimethylsilyl)oxy)trideca-2,8-diene-6,10-diynoate as a yellow
oil (0.492 g, 92%): TLC Rf 0.65 (2:1 hexanes/ethyl acetate); IR
P r ep a r a tion of (Z)-11-Hyd r oxy-N-(d ip h en yla m in o)u n -
d ec-7-en e-5,9-d iyn -1-im in e (61). Aldehyde 60 (0.350g, 1.20
mmol) was subjected to reaction conditions similar to those
for the preparation of 57 using 1,1-diphenylhydrazine hydro-
chloride (0.318 g, 1.44 mmol) and pyridine (0.116 mL, 1.44
mmol). Purification was accomplished by radial chromatog-
raphy (98:2 hexanes/ethyl acetate) to afford (Z)-10-((tert-
butyldimethylsilyl)oxy)-N-(diphenylamino)undec-7-ene-5,9-
diyn-1-imine as a pale yellow oil (0.505 g, 92%): TLC Rf 0.74
(3:1 hexanes/ethyl acetate); IR (neat) ν 2930, 2214, 1591, 1495,
1211, 1074 cm-1; 1H NMR δ 7.40-7.32 (m, 4H), 7.15-7.05 (m,
6H), 6.53 (t, J ) 5.4 Hz, 1H), 5.79-5.75 (m, 2H), 4.48 (d, J )
1.2 Hz, 2H), 2.49-2.37 (m, 4H), 1.79 (quintet, J ) 7.2 Hz, 2H),
0.90 (s, 9H), 0.12 (s, 6H); 13C NMR δ 144.1, 138.3, 129.6, 123.9,
122.2, 120.1, 117.9, 98.0, 94.7, 82.2, 78.5, 52.3, 31.7, 25.9, 25.8,
19.4, 18.2, -5.1; HRMS (EI) calcd for C29H36SiN2O (M+)
456.2597, found 456.2590.
1
(neat) ν 2953, 2214, 1728, 1660, 1257, 1099 cm-1; H NMR δ
6.96 (dt, J ) 15.6, 6.6 Hz, 1H), 5.86 (dt, J ) 15.6, 1.5 Hz, 1H),
5.74-5.72 (m, 2H), 4.67 (dq, J ) 0.6, 6.6 Hz, 1H), 3.69 (s, 3H),
2.54-2.38 (m, 4H), 1.41 (d, J ) 6.6 Hz, 3H), 0.86 (s, 9H), 0.11
(s, 3H), 0.10 (s, 3H); 13C NMR δ 166.7, 146.8, 122.0, 119.5,
118.5, 98.9, 96.1, 80.6, 78.9, 59.4, 51.4, 31.3, 25.7, 25.3, 18.7,
18.2, -4.6, -5.0; HRMS (EI) calcd for C20H30SiO3 (M+)
346.1964, found 346.1963.
Alcohol 59 was prepared like 51 using (E,Z)-12-((tert-
butyldimethylsilyl)oxy)trideca-2,8-diene-6,10-diynoate (0.415
g, 1.20 mmol), dichloromethane (10 mL), and boron trifluoride
diethyl etherate (0.440 mL, 3.58 mmol) with stirring for 1 h
to afford 59 as a pale yellow oil (0.234 g, 84%): TLC Rf 0.19
(2:1 hexanes/ethyl acetate); IR (neat) ν 3430, 2984, 2211, 1722,
(Z)-10-((tert-Butyldimethylsilyl)oxy)-N-(diphenylamino)un-
dec-7-ene-5,9-diyn-1-imine (0.500 g, 1.10 mmol) was subjected
to desilylation conditions similar to those used for the prepara-
tion of 54 using tetra-n-butylammonium fluoride (1.0 M
solution in THF, 3.30 mL, 3.30 mmol). Purification was
achieved by radial chromatography (3:1 hexanes/ethyl acetate)
to provide 61 as a pale yellow oil (0.358 g, 95%): TLC Rf 0.19
(3:1 hexanes/ethyl acetate); IR (neat) ν 3387, 2933, 2212, 1591,
1
1659, 1285 cm-1; H NMR δ 7.06 (dt, J ) 15.6, 6.6 Hz, 1H),
5.89 (dt, J ) 15.6, 1.5 Hz, 1H), 5.74-5.71 (m, 2H), 4.66 (dq, J
) 1.2, 6.6 Hz, 1H), 3.68 (s, 3H), 3.12 (bs, 1H), 2.55-2.48 (m,
2H), 2.45-2.36 (m, 2H), 1.44 (d, J ) 6.6 Hz, 3H); 13C NMR δ
167.2, 147.3, 121.8, 119.7, 118.5, 98.6, 96.2, 80.7, 79.2, 58.4,
51.6, 30.9, 24.0, 18.6; HRMS (EI) calcd for C14H16O3 (M+)
232.1100, found 232.1102.
1
1495, 1211, 1092 cm-1; H NMR δ 7.40-7.32 (m, 4H), 7.15-
7.05 (m, 6H), 6.55 (t, J ) 5.4 Hz, 1H), 5.81-5.77 (m, 2H), 4.38
(dd, J ) 6.6, 1.2 Hz, 2H), 2.53-2.42 (m, 5H), 1.76 (quintet, J
) 7.2 Hz, 2H); 13C NMR δ 144.1, 139.4, 129.6, 124.0, 122.4,
120.5, 117.9, 98.1, 94.5, 82.8, 78.7, 51.4, 31.4, 25.7, 19.2; HRMS
(EI) calcd for C23H22N2O (M+) 342.1732, found 342.1744.
Gen er a l P r oced u r e for th e [2,3] Sigm a tr op ic Rea r -
r a n gem en t Rea ction of th e En ed iyn e Su bstr a tes 51-57,
59, a n d 61. To a stirred solution of the respective enediyne
in dichloromethane (≈0.02 M) at -78° C were added trieth-
ylamine (2.0 equiv) and chlorodiphenylphosphine (1.5 equiv)
via syringe. After being stirred at -78 °C under nitrogen for
30 min, the reaction mixture was allowed to warm up to 0 °C
and stirred for an additional 30 min. The mixture was then
concentrated in vacuo at 0 °C, and the residue was dissolved
in diethyl ether (60 mL). The solution was washed with 10%
aqueous sodium bicarbonate (3 × 50 mL). The combined
organic layers were dried over anhydrous magnesium sulfate,
filtered, and evaporated in vacuo at 0 °C to provide the
respective crude enyne allene as a yellow oil.
Gen er a l P r oced u r e for th e Ta n d em En yn e Allen e-
Ra d ica l Cycliza tion Rea ction of th e En yn e Allen e Su b-
str a tes 62-67, 73, 74, a n d 78. The respective crude enyne
allene was dissolved in anhydrous benzene (6.0 mL), and the
resulting solution was transferred to a predried high-pressure
vial. The reaction mixture was degassed by passing dry
nitrogen through the solution for 20 min, and 1,4-CHD (3.00
mL, 31.7 mmol, 3.5 M) was added via syringe. The reaction
vial was sealed under nitrogen with a nylon screw cap and
heated to 37 °C for 12 h, upon which the starting material
P r ep a r a tion of (Z)-11-((ter t-Bu tyld im eth ylsilyl)oxy)-
u n d ec-7-en e-5,9-d iyn a l (60). cis-Dichloroethylene (4.30 mL,
57.5 mmol) was subjected to palladium-catalyzed coupling
reaction conditions similar to those used for the preparation
of 58 using tetrakis(triphenylphosphine)palladium(0) (0.092
g, 0.780 mmol), copper(I) iodide (0.350 g, 0.184 mmol), n-
butylamine (7.70 mL, 78.2 mmol), and 5-hexynol (4.53 g, 46.0
mmol). Purification by radial chromatography (5:1 hexanes/
ethyl acetate) provided (Z)-8-chlorooct-7-en-5-yn-1-ol as a
colorless oil (5.46 g, 75%): TLC Rf 0.22 (2:1 hexanes/ethyl
acetate); IR (neat) ν 3345, 2942, 2214, 1335, 1059 cm-1 1H
;
NMR δ 6.26 (dt, J ) 7.5, 0.6 Hz, 1H), 5.80 (dt, J ) 7.5, 2.1 Hz,
1H), 3.63 (t, J ) 6.3 Hz, 2H), 2.43-2.36 (m, 2H), 1.94 (s, 1H),
1.73-1.55 (m, 4H); 13C NMR δ 126.9, 112.3, 98.8, 74.9, 62.2,
31.6, 24.7, 19.3; HRMS (EI) calcd for C8H11OCl (M+) 158.0499,
found 158.0490.
(Z)-8-Chlorooct-7-en-5-yn-1-ol (2.00 g, 12.6 mmol) was sub-
jected to palladium-catalyzed coupling reaction conditions
similar to those described above using tetrakis(triphenylphos-
phine)palladium(0) (0.248 g, 0.214 mmol), copper(I) iodide
(0.096 g, 0.500 mmol), n-butylamine (2.10 mL, 21.4 mmol), and
3-((tert-butyldimethylsilyl)oxy)propyne (2.57 g, 15.2 mmol).
Purification by radial chromatography (5:1 hexanes/ethyl
acetate) afforded (Z)-11-((tert-butyldimethylsilyl)oxy)undec-7-
ene-5,9-diyn-1-ol as a pale yellow oil (2.80 g, 76%): TLC Rf

622 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
had been consumed on the basis of TLC. The reaction mixture
was concentrated in vacuo, and the residue was filtered
through a small amount of silica gel using a 1:4 mixture of
hexanes/ethyl acetate. The filtrate was evaporated, and the
residue was subjected to radial chromatography to provide the
respective 2,3-dihydroindene or 1,2,3,4-tetrahydronaphthalene
derivatives.
P r epar ation of 2-[2,3-Dih ydr o-5-(diph en ylph osph in yl)-
4-m eth ylin d en yl]eth yl Aceta te (70). Enyne allene 65 was
prepared from 54 (0.100 g, 0.431 mmol) according to the
general procedure for the [2,3] sigmatropic rearrangement
reaction using triethylamine (0.120 mL, 0.860 mmol) and
chlorodiphenylphosphine (0.115 mL, 0.640 mmol) in dichlo-
romethane (20 mL). Crude allene 65 was then subjected to
thermolysis according to the general procedure for the tandem
enyne allene-radical cyclization. Purification was achieved
by radial chromatography (1:3 hexanes/ethyl acetate) to
provide 70 as a pale yellow oil (0.112 g, 62% from 54): TLC
Rf 0.27 (1:4 hexanes/ethyl acetate); IR (neat) ν 2955, 2220,
1738, 1242 cm-1; 1H NMR δ 7.68-7.57 (m, 4H), 7.55-7.39 (m,
6H), 6.92 (dd, J ) 7.8, 2.4 Hz, 1H), 6.82 (dd, J ) 13.8, 7.8 Hz,
1H), 4.15 (t, J ) 6.9 Hz, 2H), 3.20 (m, 1H), 2.87 (ddd, J )
16.2, 8.7, 4.8 Hz, 1H), 2.80-2.65 (m, 1H), 2.37-2.24 (m, 1H),
P r ep a r a tion of Meth yl 2,3-Dih yd r o-5-(d ip h en ylp h os-
p h in yl)-4-m eth ylin d en e-1-a ceta te (68). Enyne allene ester
62 was prepared from 51 (0.050 g, 0.23 mmol) according to
the general procedure for the [2,3] sigmatropic rearrangement
reaction using triethylamine (0.064 mL, 0.46 mmol) and
chlorodiphenylphosphine (0.061 mL, 0.34 mmol) in dichlo-
romethane (10 mL). Crude allene 62 was then subjected to
thermolysis according to the general procedure for the tandem
enyne allene-radical cyclization. Purification was achieved
by radial chromatography (1:2 hexanes/ethyl acetate) to
provide 68 as a pale yellow oil (0.063 g, 68% from 51): TLC
Rf 0.30 (1:4 hexanes/ethyl acetate); IR (neat) ν 2955, 1736,
2.32 (s, 3H), 2.11 (m, 1H), 2.03 (s, 3H), 1.78-1.64 (m, 2H); 13
C
NMR δ 171.1, 150.7 (d, J PC ) 2.1 Hz), 145.0 (d, J PC ) 11.3
Hz), 138.9 (d, J PC ) 8.7 Hz), 133.9 (d, J PC ) 3.6 Hz), 132.4 (d,
J PC ) 14.0 Hz), 131.8 (d, J PC ) 9.2 Hz), 131.5 (d, J PC ) 3.1
Hz), 129.5, 128.4 (d, J PC ) 12.4 Hz), 120.2 (d, J PC ) 14.4 Hz),
62.8, 42.0, 33.4, 31.2, 30.1, 21.0, 18.4 (d, J PC ) 5.2 Hz); 31P
NMR δ 32.5; HRMS (EI) calcd for C26H26PO3 (M+ - H)
417.1620, found 417.1624.
1190, 1170, 752 cm-1 1H NMR δ 7.67-7.57 (m, 4H), 7.54-
;
7.38 (m, 6H), 6.90 (dd, J ) 7.8, 2.4 Hz, 1H), 6.82 (dd, J ) 13.8,
7.8 Hz, 1H), 3.67 (s, 3H), 3.65-3.52 (m, 1H), 2.85 (ddd, J )
16.2, 8.7, 4.8 Hz, 1H), 2.81-2.69 (m, 1H), 2.69 (dd, J ) 15.6,
6.0 Hz, 1H), 2.46-2.33 (m, 2H), 2.32 (s, 3H), 1.73 (m, 1H); 13
C
NMR δ 172.8, 149.8 (d, J PC ) 2.6 Hz), 145.0 (d, J PC ) 11.3
Hz), 139.0 (d, J PC ) 8.8 Hz), 133.9, 132.5 (d, J PC ) 14.0 Hz),
131.8 (d, J PC ) 9.8 Hz), 131.5 (d, J PC ) 2.6 Hz), 129.8, 128.4
(d, J PC ) 11.9 Hz), 120.1 (d, J PC ) 14.4 Hz), 51.6, 41.6, 39.4,
31.5, 29.9, 18.3 (d, J PC ) 5.2 Hz); 31P NMR (121 MHz, CDCl3)
d 32.4; HRMS (EI) calcd for C25H25PO3 (M+) 404.1541, found
404.1549.
P r ep a r a t ion of 2,3-Dih yd r o-5-(d ip h en ylp h osp h in yl)-
1-(m eth oxym eth yl)-4-m eth ylin d en e (71). Enyne allene 66
was prepared from 55 (0.080 g, 0.42 mmol) according to the
general procedure for the [2,3] sigmatropic rearrangement
reaction using triethylamine (0.117 mL, 0.840 mmol) and
chlorodiphenylphosphine (0.113 mL, 0.630 mmol) in dichlo-
romethane (20 mL). The crude allene was then subjected to
thermolysis according to the general procedure for the tandem
enyne allene-radical cyclization. Purification was accom-
plished by radial chromatography (1:3 hexanes/ethyl acetate)
to furnish 71 as a pale yellow oil (0.087 g, 55% from 55): TLC
Rf 0.28 (1:4 hexanes/ethyl acetate); IR (neat) ν 2968, 1437,
P r ep a r a t ion of Met h yl r-Met h yl-2,3-d ih yd r o-5-(d i-
p h en ylp h osp h in yl)-4-m et h ylin d en e-1-a cet a t e (69a ,b ).
Enyne allene 63 was prepared from 52 (0.080 g, 0.34 mmol)
according to the general procedure for the [2,3] sigmatropic
rearrangement reaction using triethylamine (0.095 mL, 0.68
mmol) and chlorodiphenylphosphine (0.091 mL, 0.51 mmol)
in dichloromethane (18 mL). Crude allene 63 was then
subjected to thermolysis according to the general procedure
for the tandem enyne allene-radical cyclization. Purification
was accomplished by radial chromatography (1:2 hexanes/ethyl
acetate) to afford 69a ,b as a pale yellow oil (0.101 g, 3.5:1
diastereomeric mixture, 70% combined yield from 52): TLC
Rf 0.32 (1:4 hexanes/ethyl acetate); IR (neat) ν 2953, 1732,
1437, 1192, 1170 cm-1; 1H NMR major isomer δ 7.66-7.56 (m,
4H), 7.53-7.38 (m, 6H), 6.91 (dd, J ) 7.8, 2.1 Hz, 1H), 6.82
(dd, J ) 13.8, 7.8 Hz, 1H), 3.61 (s, 3H), 3.59-3.42 (m, 1H),
2.90-2.62 (m, 3H), 2.31 (s, 3H), 2.29-2.08 (m, 1H), 1.89 (m,
1H), 1.09 (d, J ) 7.2 Hz, 3H); minor isomer δ 7.66-7.56 (m,
4H), 7.53-7.38 (m, 6H), 6.91 (dd, J ) 7.8, 2.1 Hz, 1H), 6.82
(dd, J ) 13.8, 7.8 Hz, 1H), 3.65 (s, 3H), 3.59-3.42 (m, 1H),
2.90-2.62 (m, 3H), 2.31 (s, 3H), 2.29-2.08 (m, 1H), 1.89 (m,
1H), 1.01 (d, J ) 7.2 Hz, 3H); 13C NMR major isomer δ 175.9,
148.2 (d, J PC ) 2.6 Hz), 145.6 (d, J PC ) 10.9 Hz), 138.8 (d, J PC
) 8.8 Hz), 133.8, 132.4 (d, J PC ) 14.0 Hz), 131.8 (d, J PC ) 9.3
Hz), 131.5 (d, J PC ) 2.6 Hz), 129.7, 128.4 (d, J PC ) 11.9 Hz),
121.6 (d, J PC ) 14.0 Hz), 51.5, 47.9, 42.5, 29.9, 29.1, 18.3 (d,
J PC ) 5.1 Hz), 14.2; minor isomer δ 176.0, 148.9 (d, J PC ) 2.6
Hz), 145.5 (d, J PC ) 10.9 Hz), 138.9 (d, J PC ) 8.8 Hz), 133.9,
132.4 (d, J PC ) 14.0 Hz), 131.7 (d, J PC ) 9.2 Hz), 131.5 (d, J PC
) 2.6 Hz), 129.7, 128.4 (d, J PC ) 11.9 Hz), 120.3 (d, J PC ) 14.0
Hz), 51.6, 47.3, 42.6, 30.3, 26.8, 18.3 (d, J PC ) 5.1 Hz), 12.7;
31P NMR major isomer δ 32.6; minor isomer δ 32.6; HRMS
(EI) calcd for C26H27PO3 (M+) 418.1698, found 418.1695.
P r ep a r a t ion of Met h yl r-Met h yl-2,3-d ih yd r o-5-(d i-
p h en ylp h osp h in yl)-4-m et h ylin d en e-1-a cet a t e (69a ,b ).
Enyne allene ester 64 was prepared from 53 (0.055 g, 0.24
mmol) according to the general procedure for the [2,3] sigma-
tropic rearrangement reaction using triethylamine (0.066 mL,
0.47 mmol) and chlorodiphenylphosphine (0.064 mL, 0.36
mmol) in dichloromethane (12 mL). Crude allene 64 was then
subjected to thermolysis according to the general procedure
for the tandem enyne allene-radical cyclization. Purification
was achieved by radial chromatography (1:2 hexanes/ethyl
acetate) to provide 69a ,b as a pale yellow oil (0.066 g, 3.5:1
diastereomeric mixture, 67% combined yield from 53).
1190, 1117, 752 cm-1 1H NMR δ 7.68-7.57 (m, 4H), 7.54-
;
7.39 (m, 6H), 7.03 (dd, J ) 7.8, 2.4 Hz, 1H), 6.82 (dd, J ) 13.8,
7.8 Hz, 1H), 3.57-3.35 (m, 3H), 3.34 (s, 3H), 2.93-2.70 (m,
2H), 2.32 (s, 3H), 2.31-2.17 (m, 1H), 1.85 (m, 1H); 13C NMR δ
148.9 (d, J PC ) 2.6 Hz), 145.5 (d, J PC ) 11.4 Hz), 138.8 (d, J PC
) 8.8 Hz), 134.0, 132.4 (d, J PC ) 14.0 Hz), 131.8 (d, J PC ) 9.8
Hz), 131.5 (d, J PC ) 3.1 Hz), 129.7, 128.4 (d, J PC ) 11.9 Hz),
121.0 (d, J PC ) 14.5 Hz), 76.0, 58.9, 45.6, 30.1, 28.1, 18.4 (d,
J PC ) 5.2 Hz); 31P NMR δ 32.5; HRMS (EI) calcd for C24H25
-
PO2 (M+) 376.1592, found 376.1608.
P r ep a r a tion of Meth yl 2,3-Dih yd r o-5-(d ip h en ylp h os-
p h in yl)-4-eth ylin d en e-1-a ceta te (72). Enyne allene 67 was
prepared from 59 (0.060 g, 0.26 mmol) according to the general
procedure for the [2,3] sigmatropic rearrangement reaction
using triethylamine (0.072 mL, 0.52 mmol) and chlorodiphen-
ylphosphine (0.070 mL, 0.39 mmol) in dichloromethane (13
mL). The crude allene was then subjected to thermolysis
according to the general procedure for the tandem enyne
allene-radical cyclization. Purification was achieved by radial
chromatography (1:1 hexanes/ethyl acetate) to afford 72 as a
pale yellow oil (0.056 g, 52% from 59): TLC Rf 0.35 (1:4
hexanes/ethyl acetate); IR (neat) ν 2971, 1736, 1437, 1188
1
cm-1; H NMR δ 7.67-7.58 (m, 4H), 7.54-7.38 (m, 6H), 6.91
(dd, J ) 7.8, 2.4 Hz, 1H), 6.84 (dd, J ) 13.8, 7.8 Hz, 1H), 3.68
(s, 3H), 3.64-3.51 (m, 1H), 2.98-2.77 (m, 4H), 2.72 (dd, J )
15.6, 5.7 Hz, 1H), 2.43 (dd, J ) 15.6, 8.7 Hz, 1H), 2.42-2.32
(m, 1H), 1.72 (m, 1H), 0.87 (t, J ) 7.5 Hz, 3H); 13C NMR δ
172.9, 150.4 (d, J PC ) 2.1 Hz), 145.4 (d, J PC ) 9.2 Hz), 144.8
(d, J PC ) 10.9 Hz), 134.4, 132.7 (d, J PC ) 14.0 Hz), 131.9 (d,
J PC ) 9.8 Hz), 131.5 (d, J PC ) 2.6 Hz), 129.5, 128.3 (d, J PC
)
11.9 Hz), 120.2 (d, J PC ) 14.5 Hz), 51.6, 41.4, 39.3, 31.9, 29.4,
25.6 (d, J PC ) 5.2 Hz), 13.5; 31P NMR δ 32.3; HRMS (EI) calcd
for C26H27PO3 (M+) 418.1698, found 418.1689.
P r ep a r a tion of N-(p h en ylm eth oxy)-2,3-d ih yd r o-5-(d i-
p h en ylp h osp h in yl)-4-m eth ylin d en e-1-a m in e (75). Enyne
allene 73 was prepared from 56 (0.100 g, 0.370 mmol)
according to the general procedure for the [2,3] sigmatropic
rearrangement reaction using triethylamine (0.103 mL, 0.740
mmol) and chlorodiphenylphosphine (0.100 mL, 0.560 mmol)
in dichloromethane (18 mL). Crude 73 was then subjected to

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 623
thermolysis according to the general procedure for the tandem
enyne allene-radical cyclization. Purification was accom-
plished by radial chromatography (1:2 hexanes/ethyl acetate)
to produce 75 as a pale yellow oil (0.042 g, 25% from 56): TLC
Rf 0.14 (1:4 hexanes/ethyl acetate); IR (neat) ν 2972, 1437,
anesulfonate as a pale yellow oil: TLC Rf 0.24 (3:1 hexanes/
ethyl acetate); IR (neat) ν 3285, 3065, 3028, 2940, 2239, 2110
1
cm-1; H NMR δ 3.18 (3H, s), 3.31 (1H, s), 5.12 (2H, s), 7.31
(2H, m), 7.42-7.47 (1H, m), 7.47-7.53 (1H, m); 13C NMR δ
132.7, 132.3, 129.1, 128.6, 124.9, 124.0, 87.5, 84.6, 81.7, 81.6,
58.4, 39.4; HRMS (EI) calcd for C12H10O3S (M+) 234.0351,
found 234.0367.
1
1190, 752 cm-1; H NMR δ 7.67-7.58 (m, 4H), 7.56-7.39 (m,
6H), 7.35-7.25 (m, 5H), 7.19 (dd, J ) 7.8, 2.1 Hz, 1H), 6.86
(dd, J ) 14.1, 7.8 Hz, 1H), 5.70 (bs, NH), 4.67 (s, 2H), 4.60
(dd, J ) 7.8, 5.1 Hz, 1H), 2.93 (ddd, J ) 16.5, 8.7, 5.7 Hz, 1H),
2.75 (ddd, J ) 16.5, 8.7, 5.4 Hz, 1H), 2.38-2.33 (m, 1H), 2.33
(s, 3H), 2.02 (m, 1H); 13C NMR δ 146.4, 145.6 (d, J PC ) 11.3
Hz), 139.3 (d, J PC ) 8.8 Hz), 137.6, 133.8 (d, J PC ) 4.7 Hz),
132.4 (d, J PC ) 14.0 Hz), 131.8 (d, J PC ) 9.8 Hz), 131.6 (d, J PC
) 3.1 Hz), 129.6, 128.5 (d, J PC ) 11.3 Hz), 128.4, 128.3, 127.8,
To a solution of thiophenol (0.123 mL, 0.132 g, 1.20 mmol)
in 10 mL of THF was added at room temperature a 15.1 M
aqueous sodium hydroxide solution (0.080 mL, 0.048 g, 1.20
mmol). Then a solution of 3-(2-ethynylphenyl)-2-propynyl
methanesulfonate (0.200 g, 0.85 mmol) in 5 mL of THF was
added slowly via syringe and the reaction mixture was
vigorously stirred for 1 h. The solvent was removed in vacuo
and the residue passed through a short silica gel column with
dichloromethane. Purification of the crude product by radial
chromatography with hexanes afforded 0.200 g (94%) of
1-ethynyl-2-[3-(phenylthio)-1-propynyl]benzene as a pale yel-
low oil: TLC Rf 0.56 (3:1 hexanes/ethyl acetate); IR (neat) ν
3287, 3061, 2957, 2911, 2245, 2108, 1479, 1441 cm-1; 1H NMR
δ 3.16 (1H, s), 3.89 (2H, s), 7.20-7.25 (3H, m), 7.27-7.36 (3H,
121.8 (d, J PC ) 14.5 Hz), 76.6, 66.0, 29.4, 29.4, 18.2 (d, J PC
)
5.2 Hz); 31P NMR δ 32.5; HRMS (EI) calcd for C29H28NPO2
(M+) 453.1858, found 453.1852.
P r ep a r a tion of N-(Dip h en yla m in o)-2,3-d ih yd r o-5-(d i-
p h en ylp h osp h in yl)-4-m eth ylin d en e-1-a m in e (76). Enyne
allene 74 was prepared from 57 (0.100 g, 0.300 mmol)
according to the general procedure for the [2,3] sigmatropic
rearrangement reaction using triethylamine (0.063 mL, 0.45
mmol) and chlorodiphenylphosphine (0.065mL, 0.36 mmol) in
dichloromethane (15 mL). Crude allene 74 was then subjected
to thermolysis according to the general procedure for the
tandem enyne allene-radical cyclization. Purification was
achieved by radial chromatography (1:2 hexanes/ethyl acetate)
to furnish 76 as a pale yellow oil (0.090 g, 58% from 57): TLC
Rf 0.17 (1:4 hexanes/ethyl acetate); IR (neat) ν 3378, 2940,
m), 7.43-7.46 (1H, m), 7.50-7.54 (2H, m);
13C NMR δ 135.3,
132.4, 132.1, 130.1, 128.9, 128.4, 127.8, 126.7, 125.9, 124.5,
89.5, 81.9, 81.8, 80.9, 23.6; HRMS (EI) calcd for C17H12S (M+)
248.0660, found 248.0668.
m-Chloroperbenzoic acid (0.229 g, 1.33 mmol) was dissolved
in 10 mL of dichloromethane, and the solution was cooled to
0 °C. To this mixture was added via syringe a solution of
1-ethynyl-2-[3-(phenylthio)-1-propynyl]benzene (0.150 g, 0.60
mmol) in 3 mL of dichloromethane, and the reaction mixture
was stirred for 1 h at 0 °C. Then the solution was passed
through a short Florisil column with dichloromethane. The
crude product was purified by radial chromatography with an
80:20 mixture of hexanes/ethyl acetate to afford 0.164 g (97%)
of 81 as a pale yellow oil: TLC Rf 0.22 (3:1 hexanes/ethyl
acetate); IR (neat) ν 3283, 3063, 2953, 2907, 2230, 2108, 1323,
1138 cm-1; 1H NMR δ 3.17 (1H, s), 4.24 (2H, s), 7.25-7.28 (2H,
m), 7.30-7.34 (1H, m), 7.43-7.46 (1H, m), 7.52-7.58 (2H, m),
7.63-7.69 (1H, m), 8.02-8.06 (2H, m); 13C NMR δ 137.8, 134.1,
132.6, 132.3, 129.1, 129.0, 128.7, 128.5, 124.8, 124.6, 85.8, 81.5,
81.4, 80.7, 49.5; HRMS (EI) calcd for C17H12O2S (M+) 280.0558,
found 280.0579.
P r ep a r a tion of 2-[(P h en ylsu lfon yl)m eth yl]n a p h th a -
len e (82) via Ta n d em Acetylen e Isom er iza tion -En yn e
Allen e Cycliza tion of 1-Eth yn yl-2-[3-(p h en ylsu lfon yl)-1-
p r op yn yl]ben zen e (81). A stirred solution of 1-ethynyl-2-
[3-(phenylsulfonyl)-1-propynyl]benzene (81) (0.075 g, 0.27
mmol) in 4.8 mL of anhydrous benzene in a pressure vial was
degassed with dry nitrogen for 30 min. Then triethylamine
(0.186 mL, 0.135 g, 1.34 mmol) and 1,4-CHD (2.480 mL, 2.101
g, 26.21 mmol) were added via syringe and the vial was sealed
with a Teflon screw cap. The reaction mixture was heated at
30 °C for 11 h. The volatile components were removed in
vacuo, and the residue was passed through a short silica gel
column with a 1:1 mixture of hexanes/ethyl acetate. Subject-
ing the crude product to radial chromatography with an 80:
20 mixture of hexanes/ethyl acetate yielded 0.051 g (68%) of
1
1589, 1495, 1192 cm-1; H NMR δ 7.68-7.57 (m, 4H), 7.57-
7.39 (m, 6H), 7.30-7.22 (m, 4H), 7.12-6.94 (m, 7H), 6.82 (dd,
J ) 14.1, 7.8 Hz, 1H), 4.51 (dd, J ) 6.6, 3.6 Hz, 1H), 4.17 (bs,
1H), 3.15-3.00 (m, 1H), 2.79 (ddd, J ) 15.9, 8.4, 4.5 Hz, 1H),
2.39 (s, 3H), 2.25-1.98 (m, 2H); 13C NMR δ 147.7, 147.2 (d,
J PC ) 2.6 Hz), 145.9 (d, J PC ) 11.3 Hz), 139.3 (d, J PC ) 8.3
Hz), 133.8 (d, J PC ) 2.6 Hz), 132.5 (d, J PC ) 14.0 Hz), 131.8
(d, J PC ) 9.8 Hz), 131.6 (d, J PC ) 2.6 Hz), 129.5, 129.0, 128.4
(d, J PC ) 11.9 Hz), 122.3, 121.4 (d, J PC ) 13.9 Hz), 120.3, 62.2,
30.7, 29.6, 18.4 (d, J PC ) 4.7 Hz); 31P NMR δ 32.5; HRMS (EI)
calcd for C34H31N2PO (M+) 514.2174, found 514.2168.
P r ep a r a tion of N-(Dip h en yla m in o)-6-(d ip h en ylp h os-
p h in y l)-5-m e t h y l-1,2,3,4-t e t r a h y d r o n a p h t h a le n e -1-
a m in e (79). Enyne allene 78 was prepared from 77 (0.100 g,
0.290 mmol) according to the general procedure for the [2,3]
sigmatropic rearrangement reaction using triethylamine (0.061
mL, 0.44 mmol) and chlorodiphenylphosphine (0.063 mL, 0.35
mmol) in dichloromethane (15 mL). Crude allene 78 was then
subjected to thermolysis according to the general procedure
for the tandem enyne allene-radical cyclization. Purification
was acomplished by radial chromatography (1:1 hexanes/ethyl
acetate) to afford 79 as a pale yellow oil (0.034 g, 22% from
77): TLC Rf 0.25 (1:4 hexanes/ethyl acetate); IR (neat) ν 3378,
1
2944, 1590, 1485, 1192 cm-1; H NMR δ 7.65-7.56 (m, 4H),
7.54-7.38 (m, 6H), 7.32-7.10 (m, 8H), 7.03-6.96 (m, 2H),
6.78-6.70 (m, 2H), 3.97 (m, 1H), 2.87-2.76 (m, 1H), 2.53-
2.38 (m, 1H), 2.36 (s, 3H), 2.34-2.10 (m, 2H), 1.90-1.80 (m,
1H), 1.54 (m, 1H); 13C NMR δ 148.1, 142.1 (d, J PC ) 8.3 Hz),
139.8 (d, J PC ) 2.6 Hz), 139.2 (d, J PC ) 10.3 Hz), 133.8 (d, J PC
) 18.1 Hz), 132.5 (d, J PC ) 20.1 Hz), 131.9 (d, J PC ) 9.8 Hz),
131.6 (d, J PC ) 6.2 Hz), 130.8 (d, J PC ) 13.4 Hz), 129.2, 128.5
(d, J PC ) 11.9 Hz), 126.3 (d, J PC ) 13.4 Hz), 122.5, 120.6, 54.3,
26.9, 25.0, 18.4 (d, J PC ) 6.2 Hz), 18.0; 31P NMR δ 32.9; HRMS
(EI) calcd for C35H33N2PO (M+) 528.2330, found 528.2336.
P r ep a r a tion of 1-Eth yn yl-2-[3-(p h en ylsu lfon yl)-1-p r o-
p yn yl]ben zen e (81). 3-(2-Ethynylphenyl)-2-propyn-1-ol (36)
(0.145 g, 0.93 mmol) was dissolved in 4 mL of dichloromethane,
and the solution was cooled to 0 °C under nitrogen. To this
solution was added triethylamine (0.181 mL, 0.132 g, 1.30
mmol) via syringe. Then methanesulfonyl chloride (0.093 mL,
0.138 g, 1.21 mmol) was added slowly via syringe and the
reaction mixture was stirred for 1 h at room temperature. The
solvent was removed in vacuo and the residue passed through
a short silica gel column with a 1:1 mixture of hexanes/ethyl
acetate. Purification of the crude product by radial chroma-
tography with a 90:10 mixture of hexanes/ethyl acetate af-
forded 0.204 g (94%) of 3-(2-ethynylphenyl)-2-propynyl meth-
82 as a colorless solid: TLC Rf
0.22 (3:1 hexanes/ethyl acetate);
1
IR ν 3052, 2932, 2857, 1377, 1150 cm-1; H NMR δ 4.45 (2H,
s), 7.18 (1H, dd, J ) 8.3, 2.0 Hz), 7.36-7.43 (2H, m), 7.46 (2H,
m), 7.51 (1H, s), 7.54-7.60 (1H, m), 7.60-7.63 (2H, m), 7.67-
7.74 (2H, m), 7.77-7.81 (1H, m);
13C NMR δ 137.8, 133.7,
133.0, 133.0, 130.5, 128.9, 128.6, 128.3, 127.9, 127.8, 127.6,
126.7, 126.4, 125.5, 63.0; HRMS (EI) calcd for C17H14O2S (M+)
282.0744, found 282.0729. Anal. Calcd for C17H14O2S: C,
72.31; H, 5.00; S, 11.36. Found: C, 72.39; H, 5.06; S, 11.44.
P r ep a r a tion of 5-[2-[3-(P h en ylth io)-1-p r op yn yl]p h en -
yl]-4-p en tyn a l (83). 3-(2-Iodophenyl)-2-propyn-1-ol (8) (1.001
g, 3.88 mmol) was subjected to coupling conditions similar to
those for the preparation of 8 using triethylamine (1.622 mL,
1.178 g, 11.64 mmol), bis(triphenylphosphine)palladium(II)
chloride (0.082 g, 0.12 mmol), copper(I) iodide (0.074 g, 0.39
mmol), and 5-((tert-butyldimethylsilyl)oxy)-1-pentyne (0.923 g,
4.65 mmol) Purification by radial chromatography with a 90:
10 mixture of hexanes/diethyl ether afforded 1.249 g (98%) of
3-[2-5-((tert-butyldimethylsilyl)oxy)-1-pentynyl)phenyl]-2-pro-

624 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
pyn-1-ol as a pale yellow oil: TLC Rf 0.36 (3:1 hexanes/ethyl
acetate); IR (neat) ν 3385 (br), 3063, 2953, 2930, 2859, 2247,
2232 cm-1; 1H NMR δ 0.06 (6H, s), 0.89 (9H, s), 1.84 (2H, q, J
) 6.6 Hz), 2.42 (1H, s, br), 2.51 (2H, t, J ) 6.8 Hz), 3.84 (2H,
t, J ) 6.5 Hz), 4.50 (2H, s), 7.16-7.24 (2H, m), 7.34-7.40 (2H,
m); 13C NMR δ 131.8, 131.5, 128.0, 127.2, 126.4, 125.1, 94.0,
91.0, 84.2, 79.6, 61.9, 51.4, 31.6, 25.9, 18.3, 15.9, -5.3; HRMS
(EI) calcd for C19H25O2Si (M+ - CH3) 313.1624, found 313.1619.
This compound was prepared by a mesylation reaction
similar to that used for the preparation of 81 using 3-[2-(5-
((tert-butyldimethylsilyl)oxy)-1-pentynyl)phenyl]-2-propyn-1-
ol (0.400 g, 1.22 mmol), dichloromethane (10 mL), triethyl-
amine (0.238 mL, 0.172 g, 1.70 mmol), and methanesulfonyl
chloride (0.123 mL, 0.181 g, 1.58 mmol) Purification afforded
0.465 g (94%) of 3-[2-((5-(tert-butyldimethylsilyl)oxy)-1-pentyn-
yl)phenyl]-2-propynyl methanesulfonate as a pale yellow oil:
TLC Rf 0.38 (3:1 hexanes/ethyl acetate); IR (neat) ν 3063, 3028,
2953, 2932, 2895, 2232, 1366, 1177 cm-1; 1H NMR δ 0.05 (6H,
s), 0.89 (9H, s), 1.81 (2H, m), 2.53 (2H, t, J ) 7.1 Hz), 3.18
(3H, s), 3.75 (2H, t, J ) 6.1 Hz), 5.11 (2H, s), 7.19-7.31 (2H,
m), 7.38-7.43 (2H, m); 13C NMR δ 132.2, 132.1, 129.1, 127.3,
127.0, 123.3, 95.0, 88.3, 83.9, 78.9, 61.5, 58.5, 39.2, 31.7, 25.9,
18.3, 16.0, -5.4.
To a solution of thiophenol (0.148 mL, 0.159 g, 1.45 mmol)
in 20 mL of THF was added at room temperature a 15.1 M
aqueous sodium hydroxide solution (0.096 mL, 0.058 g, 1.45
mmol). Then a solution of 3-[2-(5-((tert-butyldimethylsilyl)-
oxy)-1-pentynyl)phenyl]-2-propynyl methanesulfonate (0.420
g, 1.03 mmol) in 5 mL of THF was added slowly via syringe
and the reaction mixture was vigorously stirred for 1 h. The
solvent was removed in vacuo and the residue passed through
a silica gel column with dichloromethane. Purification of the
crude product by radial chromatography with hexanes afforded
0.422 g (97%) of 1-[5-((tert-butyldimethylsilyl)oxy)-1-pentynyl]-
2-[3-(phenylthio)-1-propynyl]benzene as a pale yellow oil: TLC
Rf 0.66 (3:1 hexanes/ethyl acetate); IR (neat) ν 3061, 2951,
2930, 2897, 2857, 2230, 1479, 1441 cm-1; 1H NMR δ 0.05 (6H,
s), 0.88 (9H, s), 1.78 (2H, q, J ) 6.5 Hz), 2.47 (2H, t, J ) 7.1
Hz), 3.73 (2H, t, J ) 6.1 Hz), 3.88 (2H, s), 7.17 (2H, m), 7.22-
7.25 (1H, m), 7.28-7.36 (4H, m), 7.49-7.53 (2H, m); 13C NMR
δ 135.5, 132.0, 131.7, 130.1, 128.9, 127.8, 127.1, 126.7, 126.5,
125.2, 94.2, 88.7, 82.5, 79.3, 61.7, 31.8, 25.9, 23.9, 18.3, 16.0,
-5.3; HRMS (EI) calcd for C26H32OSSi (M+) 420.1943, found
420.1962.
To a solution of 1-[5-((tert-butyldimethylsilyl)oxy)-1-pentyn-
yl]-2-[3-(phenylthio)-1-propynyl]benzene (0.410 g, 0.97 mmol)
were added 6 mL of acetic acid, 2 mL of water, and 2 mL of
THF, and the reaction mixture was stirred at room temper-
ature, until no starting material could be detected by TLC (4-7
h). Then THF was removed in vacuo, 25 mL of water and 25
mL of dichloromethane were added to the residue, and the
organic layer was washed several times with sodium bicarbon-
ate. The aqueous layer was extracted twice with dichlo-
romethane (20 mL each). The organic layers were combined,
dried over magnesium sulfate, and concentrated. The residue
was subjected to radial chromatography with a 70:30 mixture
of hexanes/diethyl ether to afford 0.272 g (91%) of 5-[2-[3-
(phenylthio)-1-propynyl]phenyl]-4-pentyn-1-ol as a pale yellow
oil: TLC Rf 0.15 (3:1 hexanes/ethyl acetate); IR (neat) ν 3378
(br), 3059, 3022, 2945, 2878, 2228, 1481, 1441 cm-1; 1H NMR
δ 1.62 (1H, s), 1.82 (2H, q, J ) 6.5 Hz), 2.52 (2H, t, J ) 6.7
Hz), 3.82 (2H, t, J ) 6.1 Hz), 3.89 (2H, s), 7.18 (2H, m), 7.22-
7.25 (1H, m), 7.28-7.36 (4H, m), 7.49-7.53 (2H, m); 13C NMR
δ 135.3, 132.0, 131.7, 130.1, 128.9, 127.8, 127.2, 126.8, 126.1,
125.1, 93.5, 88.7, 82.5, 79.8, 61.5, 31.1, 23.8, 16.1; HRMS (EI)
calcd for C20H18OS (M+) 306.1078, found 306.1097.
A dry 25 mL flask under nitrogen was charged with a
solution of oxalyl chloride in dichloromethane (2 M) (0.605 mL,
0.153 g, 1.21 mmol) and 15 mL of dichloromethane. This
solution was cooled to -78 °C. Then a solution of dimethyl
sulfoxide (0.172 mL, 0.189 g, 2.42 mmol) in 3 mL of dichlo-
romethane was slowly added via syringe and the mixture was
stirred for 15 min. Then a solution of 5-[2-[3-(phenylthio)-1-
propynyl]phenyl]-4-pentyn-1-ol (0.285 g, 0.93 mmol) in 5 mL
of dichloromethane was slowly added via syringe, and the
reaction mixture was stirred for an additional 25 min, before
triethylamine (0.648 mL, 0.471 g, 4.65 mmol) was added at
once via syringe. The mixture was stirred for 1 h at -78 °C
and then allowed to warm to 0 °C, and 2 mL of a saturated
ammonium chloride solution was added. After the mixture
was extracted three times with dichloromethane, the organic
layers were combined and dried over magnesium sulfate. The
crude product was subjected to radial chromatography with a
90:10 mixture of hexanes/ethyl acetate to afford 0.260 g (92%)
of 83 as a pale yellow oil: TLC Rf 0.33 (3:1 hexanes/ethyl
acetate); IR (neat) ν 3059, 2909, 2827, 2729, 2231, 1725, 1481,
1439 cm-1; 1H NMR δ 2.67 (4H, s), 3.89 (2H, s), 7.16-7.24 (3H,
m), 7.27-7.36 (4H, m), 7.48-7.53 (2H, m), 9.77 (1H, s); 13C
NMR δ 200.5, 135.4, 131.9, 131.7, 129.9, 128.9, 127.8, 127.4,
126.7, 125.8, 125.3, 91.9, 88.9, 82.3, 80.0, 42.4, 23.7, 12.8;
HRMS (EI) calcd for C20H16OS (M+) 304.0922, found 304.0936.
P r ep a r a tion of Meth yl (E)-7-[2-[3-(P h en ylsu lfon yl)-1-
pr opyn yl]ph en yl]h ept-2-en -6-yn oate (84). Trimethyl phos-
phonoacetate (0.136 mL, 0.153 g, 0.84 mmol) was dissolved in
4 mL of acetonitrile. To this solution were added under
nitrogen lithium chloride (0.047 g, 1.12 mmol) and 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) (0.125 mL, 0.128 g, 0.84
mmol), and the reaction mixture was stirred at room temper-
ature for 15 min. Then a solution of 5-[2-[3-(phenylthio)-1-
propynyl]phenyl]-4-pentynal (83) (0.170 g, 0.56 mmol) in 2 mL
of acetonitrile was added via syringe and the reaction stirred
for 1 min. The reaction mixture was passed through a short
silica gel column with a 1:1 mixture of hexanes/ethyl acetate.
Purification of the crude product by radial chromatography
with a 97:3 mixture of hexanes/ethyl acetate afforded 0.165 g
(82%) of (E)-7-[2-[3-(phenylthio)-1-propynyl]phenyl]hept-2-en-
6-ynoate as a pale yellow oil: TLC Rf 0.42 (3:1 hexanes/ethyl
acetate); IR (neat) ν 3059, 3023, 2949, 2911, 2843, 2232, 1723,
1659, 1481, 1439 cm-1; 1H NMR δ 2.42-2.55 (4H, m), 3.71 (3H,
s), 3.90 (2H, s), 5.90 (1H, dt, J ) 15.6, 1.5 Hz), 7.03 (1H, dt, J
) 15.6, 6.6 Hz), 7.16-7.24 (3H, m), 7.27-7.36 (4H, m), 7.48-
7.53 (2H, m); 13C NMR δ 166.8, 147.1, 135.5, 131.9, 131.8,
130.0, 128.9, 127.8, 127.4, 126.7, 126.0, 125.3, 121.9, 92.4, 88.9,
82.4, 80.2, 51.4, 31.3, 23.7, 18.5; HRMS (EI) calcd for C23H20O2S
(M+) 360.1184, found 360.1189.
m-Chloroperbenzoic acid (0.126 g, 0.73 mmol) was dissolved
in 10 mL of dichloromethane, and the solution was cooled to
0 °C. To this mixture was added via syringe a solution of
methyl (E)-7-[2-[3-(phenylthio)-1-propynyl]phenyl]hept-2-en-
6-ynoate (0.120 g, 0.33 mmol), and the reaction was stirred
for 1 h at 0 °C. Then the solution was passed through a short
Florisil column with dichloromethane. The crude product was
purified by radial chromatography with an 80:20 mixture of
hexanes/ethyl acetate to afford 0.110 g (84%) of 84 as a pale
yellow oil: TLC Rf
0.52 (1:1 hexanes/ethyl acetate); IR (neat)
ν 3065, 2953, 2911, 2851, 2255, 1721, 1659, 1325, 1163 cm-1
;
1H NMR δ 2.47 (2H, m), 2.55-2.60 (2H, m), 3.72 (3H, s), 4.27
(2H, s), 5.91 (1H, dt, J ) 15.6, 1.6 Hz), 7.03 (1H, dt, J ) 15.6,
6.6 Hz), 7.15-7.29 (3H, m), 7.36 (1H, m), 7.52-7.58 (2H, m),
7.66 (1H, m), 8.02-8.06 (2H, m); 13C NMR δ 166.8, 147.1,
137.9, 134.0, 132.1, 132.0, 129.0, 129.0, 128.6, 127.4, 126.4,
124.0, 121.9, 93.0, 86.3, 80.2, 79.8, 51.5, 49.5, 31.1, 18.5; HRMS
(EI) calcd for C23H20O4S (M+) 392.1082, found 392.1101.
P r ep a r a tion of Meth yl (E)-7-[2-[3-(P h en ylsu lfon yl)-1-
p r op yn yl]p h en yl]-3-m eth ylh ep t-2-en -6-yn oa te (85). 5-[2-
[3-(Phenylthio)-1-propynyl]phenyl]-4-pentynal (83) (0.150 g,
0.49 mmol) was subjected to Horner-Emmons reaction condi-
tions similar to those used in the preparation of 84 using
trimethyl methylphosphonoacetate (0.145 g, 0.74 mmol), ac-
etonitrile (4 mL), lithium chloride (0.042 g, 0.99 mmol), and
DBU (0.111 mL, 0.113 g, 0.74 mmol). Purification afforded
0.114 g (62%) of the E isomer of methyl (E)-7-[2-[3-(phenylthio)-
1-propynyl]phenyl]-3-methylhept-2-en-6-ynoate (next to 0.039
g [21%] of the corresponding Z isomer) as a pale yellow oil:
TLC Rf 0.40 (3:1 hexanes/ethyl acetate); IR (neat) ν 3059, 3000,
2950, 2839, 2231, 1717, 1653, 1481, 1437 cm-1; 1H NMR δ 1.86
(3H, d, J ) 1.5 Hz), 2.42-2.55 (4H, m), 3.73 (3H, s), 3.89 (2H,
s), 6.83 (1H, m), 7.15-7.26 (3H, m), 7.28-7.38 (4H, m), 7.50-
7.54 (2H, m); 13C NMR δ 168.4, 140.1, 135.5, 131.9, 131.8,
130.0, 128.9, 128.7, 127.8, 127.3, 126.7, 126.1, 125.3, 93.0, 88.9,
82.4, 79.8, 51.8, 28.1, 23.8, 18.9, 12.6; HRMS (EI) calcd for
C24H22O2S (M+) 374.1341, found 374.1328.

Tandem Enyne Allene-Radical Cyclization
J . Org. Chem., Vol. 62, No. 3, 1997 625
The sulfone was prepared by an m-CPBA oxidation similar
to that used for the preparation of 84 using m-chloroperbenzoic
acid (0.096 g, 0.56 mmol), dichloromethane (10 mL), and
methyl (E)-7-[2-[3-(phenylthio)-1-propynyl]phenyl]-3-methyl-
hept-2-en-6-ynoate (0.095 g, 0.25 mmol) to afford 0.073 g (71%)
of 85 as a pale yellow oil: TLC Rf 0.57 (1:2 hexanes/ethyl
acetate); IR (neat) ν 3065, 2996, 2951, 2907, 2843, 2255, 1711,
0.52 mmol) was dissolved in 15 mL of dichloromethane, and
the solution was cooled to 0 °C. Then a 1 M solution of
diisobutylaluminum hydride in n-hexane (1.290 mL, 0.183 g,
1.29 mmol) was slowly added via syringe and the reaction
mixture was stirred for 30 min at 0 °C. Next, 1 mL of a
concentrated aqueous potassium fluoride solution was added
and the biphasic mixture was stirred for an additional 10 min.
After the aqueous layer was extracted several times with
dichloromethane, the organic layers were combined and dried
over magnesium sulfate. Purification of the crude product by
radial chromatography with a 70:30 mixture of hexanes/diethyl
ether afforded 0.124 g (72%) of (E)-7-[2-[3-(phenylthio)-1-
propynyl]phenyl]hept-2-en-6-yn-1-ol as a pale yellow oil: TLC
Rf 0.32 (2:1 hexanes/ethyl acetate); IR (neat) ν 3385 (br), 3059,
2924, 2868, 2232, 1584, 1481, 1441 cm-1; 1H NMR δ 1.45 (1H,
s, br), 2.29-2.36 (2H, m), 2.44-2.49 (2H, m), 3.88 (2H, s), 4.08
(2H, d, br), 5.66-5.85 (2H, m), 7.18 (2H, m), 7.19-7.24 (1H,
m), 7.28-7.37 (4H, m), 7.49-7.53 (2H, m); 13C NMR δ 135.4,
132.0, 131.8, 130.9, 130.3, 130.1, 128.9, 127.8, 127.2, 126.8,
126.3, 125.2, 93.6, 88.7, 82.5, 79.7, 63.5, 31.4, 23.9, 19.6; HRMS
(EI) calcd for C22H20OS (M+) 332.1235, found 332.1263.
This compound was prepared by an m-CPBA oxidation
similar to that used for the preparation of 84 using m-
chloroperbenzoic acid (0.126 g, 0.73 mmol), dichloromethane
(10 mL), and (E)-7-[2-[3-(phenylthio)-1-propynyl]phenyl]hept-
2-en-6-yn-1-ol (0.110 g, 0.33 mmol). The solution was passed
through a short Florisil column with a 3:1 mixture of ethyl
acetate/hexanes. The crude product was purified by radial
chromatography with a 65:35 mixture of hexanes/ethyl acetate
to afford 0.055 g (46%) of 87 as a pale yellow oil: TLC Rf 0.47
(1:2 hexanes/ethyl acetate); IR (neat) ν 3405 (br), 3063, 2953,
2926, 2870, 2243, 1586, 1325, 1138 cm-1; 1H NMR δ 1.74 (1H,
s, br), 2.28-2.34 (2H, m), 2.47-2.52 (2H, m), 4.09 (2H, s), 4.23
(2H, s), 5.67 (2H, m), 7.14-7.27 (3H, m), 7.34-7.37 (1H, m),
1
1649, 1325, 1138 cm-1; H NMR δ 1.84 (3H, d, J ) 1.5 Hz),
2.45 (2H, m), 2.53-2.58 (2H, m), 3.72 (3H, s), 4.24 (2H, s), 6.82
(1H, tq, J ) 7.3, 1.5 Hz), 7.15-7.28 (3H, m), 7.34-7.42 (1H,
m), 7.51-7.58 (2H, m), 7.65 (1H, m), 8.02-8.07 (2H, m); 13C
NMR δ 168.5, 140.2, 137.9, 134.1, 133.7, 132.1, 132.0, 130.2,
129.8, 129.0, 128.8, 128.6, 128.2, 127.4, 126.5, 124.0, 93.6, 86.3,
80.1, 79.4, 51.8, 49.5, 27.8, 18.9, 12.6; HRMS (EI) calcd for
C24H22O4S (M+) 406.1239, found 406.1243.
P r ep a r a tion of (E)-7-[2-[3-(P h en ylsu lfon yl)-1-p r op yn -
yl]p h en yl]h ep t -2-en -6-yn en it r ile/(Z)-7-[2-(3-(P h en ylsu l-
fon yl)-1-p r op yn yl)p h en yl]h ep t-2-en -6-yn en itr ile (86). Po-
tassium tert-butoxide (0.106 g, 0.95 mmol) was dissolved in
10 mL of THF. To this solution was added diethyl (cyano-
methyl)phosphonate (0.163 mL, 0.178 g, 1.01 mmol) under
nitrogen, and the reaction mixture was stirred at room
temperature for 30 min. Then a solution of 5-[2-[3-(phenyl-
thio)-1-propynyl]phenyl]-4-pentynal (83) (0.180 g, 0.59 mmol)
in 3 mL of THF was added via syringe and the reaction stirred
for 1 min. The solvent was removed in vacuo, and the residue
was passed through a short silica gel column with a 2:1
mixture of ethyl acetate/hexanes. Purification of the crude
product by radial chromatography with a 96:4 mixture of
hexanes/ethyl acetate afforded 0.147 g (76%) of (E)-7-[2-[3-
(phenylthio)-1-propynyl]phenyl]hept-2-en-6-ynenitrile/(Z)-7-[2-
[3-(phenylthio)-1-propynyl]phenyl]hept-2-en-6-ynenitrile as a
pale yellow oil (3:2 mixture of cis/trans isomers): TLC Rf 0.37
(3:1 hexanes/ethyl acetate); IR (neat) ν 3061, 2951, 2922, 2222,
1624, 1584, 1481, 1441 cm-1; 1H NMR cis isomer δ 2.40-2.57
(3H, m), 2.63-2.70 (1H, m), 3.88 (2H, s), 5.36 (1H, dt, J )
11.0, 1.2 Hz), 6.66 (1H, dt, J ) 11.0, 7.6 Hz), 7.18-7.25 (3H,
m), 7.28-7.38 (4H, m), 7.48-7.53 (2H, m); trans isomer δ
2.40-2.57 (3H, m), 2.63-2.70 (1H, m), 3.90 (2H, s), 5.41 (1H,
dt, J ) 16.4, 1.5 Hz), 6.78 (1H, dt, J ) 16.4, 6.6 Hz), 7.18-
7.25 (3H, m), 7.28-7.38 (4H, m), 7.48-7.53 (2H, m); 13C NMR
cis isomer δ 152.9, 135.4, 132.0, 131.8, 129.9, 128.9, 127.9,
127.5, 126.8, 125.7, 125.2, 117.3, 100.6, 91.5, 88.8, 82.4, 80.7,
30.6, 23.8, 18.6; trans isomer δ 153.5, 135.4, 132.0, 131.7, 129.9,
128.9, 127.9, 127.6, 126.7, 125.6, 125.2, 115.8, 101.0, 91.3, 88.9,
82.4, 80.8, 32.1, 23.8, 18.1; HRMS (EI) calcd for C22H17NS (M+)
327.1084, found 360.1083.
7.52-7.58 (2H, m), 7.63-7.69 (1H, m), 8.02-8.06 (2H, m); 13
C
NMR δ 137.8, 134.1, 132.1, 132.0, 130.5, 130.4, 129.0, 129.0,
128.6, 127.3, 126.7, 123.9, 94.3, 86.5, 79.9, 79.3, 63.4, 49.6, 31.2,
19.6; HRMS (EI) calcd for C22H20O3S (M+) 364.1133, found
364.1133.
P r ep a r a tion of N-(P h en ylm eth oxy)-5-[2-[3-(p h en ylsu l-
fon yl)-1-p r op yn yl]p h en yl]p en t-4-yn -1-im in e (88). To a
solution of 5-[2-[3-(phenylthio)-1-propynyl]phenyl]-4-pentynal
(83) (0.200 g, 0.66 mmol) in 5 mL of dichloromethane were
added O-benzylhydroxylamine hydrochloride (0.147 g, 0.92
mmol) and pyridine (0.074 mL, 0.073 g, 0.92 mmol), and the
reaction mixture was stirred at room temperature for 30 min.
Then the heterogeneous mixture was passed through a Florisil
column with dichloromethane. Purification of the crude
product by radial chromatography with a 90:10 mixture of
hexanes/ethyl acetate afforded 0.253 g (94%) of N-(phenyl-
methoxy)-5-[2-[3-(phenylthio)-1-propynyl]phenyl]pent-4-yn-1-
imine as a pale yellow oil (1:1 mixture of syn/anti isomers):
TLC Rf 0.52 (2:1 hexanes/ethyl acetate); IR (neat) ν 3063, 3032,
2918, 2875, 2242, 1480, 1439 cm-1; 1H NMR δ 2.43-2.68 (4H,
m), 3.86 (1H, s), 3.88 (1H, s), 5.06 (1H, s), 5.11 (1H, s), 6.90
(1/2H, t, J ) 4.9 Hz), 7.17-7.24 (3H, m), 7.27-7.37 (9H, m),
7.48-7.52 (2H, m), 7.64 (1/2H, t, J ) 5.7 Hz); 13C NMR δ 150.4,
149.8, 137.9, 137.5, 135.4, 132.0, 131.9, 131.7, 131.7, 130.1,
130.0, 128.9, 128.3, 128.2, 127.9, 127.8, 127.7, 127.4, 127.4,
126.7, 126.0, 125.4, 125.3, 92.4, 92.2, 89.0, 88.9, 82.4, 82.3, 80.3,
80.3, 75.8, 75.6, 28.8, 25.1, 23.7, 23.7, 17.4, 16.6; HRMS (EI)
calcd for C27H23NOS (M+) 409.1500, found 409.1506.
The sulfone was prepared by an m-CPBA oxidation similar
to that used for the preparation of 84 using m-chloroperbenzoic
acid (0.139 g, 0.81 mmol), dichloromethane (10 mL), (E)-7-[2-
[3-(phenylthio)-1-propynyl]phenyl]hept-2-en-6-ynenitrile, and
(Z)-7-[2-[3-(phenylthio)-1-propynyl]phenyl]hept-2-en-6-yneni-
trile (0.120 g, 0.37 mmol). The solution was passed through
a short Florisil column with a 1:1 mixture of hexanes/ethyl
acetate. The crude product was purified by radial chroma-
tography with an 80:20 mixture of hexanes/ethyl acetate to
afford 0.111 g (84%) of 86 as a pale yellow oil (3:2 mixture of
cis/trans isomers): TLC Rf 0.52 (1:1 hexanes/ethyl acetate);
IR (neat) ν 3065, 2951, 2909, 2843, 2224, 1634, 1586, 1323,
1163 cm-1 1H NMR cis isomer δ 2.46-2.54 (1H, m), 2.59-
;
2.72 (3H, m), 4.22 (2H, s), 5.40 (1H, dt, J ) 11.0, 1.2 Hz), 6.65
(1H, dt, J ) 11.0, 7.3 Hz), 7.15-7.28 (3H, m), 7.35-7.39 (1H,
m), 7.51-7.57 (2H, m), 7.62-7.68 (1H, m), 8.01-8.05 (2H, m);
trans isomer δ 2.59-2.72 (4H, m), 4.23 (2H, s), 5.46 (1H, dt, J
) 16.4, 1.5 Hz), 6.80 (1H, dt, J ) 16.4, 6.6 Hz), 7.15-7.28 (3H,
m), 7.35-7.39 (1H, m), 7.51-7.57 (2H, m), 7.62-7.68 (1H, m),
8.01-8.05 (2H, m); 13C NMR cis isomer δ 152.8, 137.8, 134.1,
132.1, 132.0, 129.0, 128.8, 128.7, 127.5, 126.1, 123.9, 117.4,
100.7, 92.2, 86.3, 80.1, 80.0, 49.5, 30.6, 18.6; trans isomer δ
153.7, 137.8, 134.1, 132.1, 131.9, 129.0, 128.8, 128.7, 127.6,
126.0, 124.0, 115.8, 101.0, 92.1, 86.3, 80.3, 80.0, 49.5, 31.9, 18.2;
HRMS (EI) calcd for C22H17NO2S (M+) 359.0980, found
359.0955.
This compound was prepared by an m-CPBA oxidation
similar to that used for the preparation of 86 using m-chlo-
roperbenzoic acid (0.232 g, 1.34 mmol), dichloromethane (17
mL), and N-(phenylmethoxy)-5-[2-[3-(phenylthio)-1-propynyl]-
phenyl]pent-4-yn-1-imine (0.250 g, 0.61 mmol) to afford 0.183
g (68%) of 88 as a pale yellow oil (1:1 mixture of syn/anti
isomers): TLC Rf 0.52 (1:1 hexanes/ethyl acetate); IR (neat) ν
3061, 3028, 2940, 2907, 2232, 1325, 1138 cm-1 1H NMR δ
;
2.38-2.45 (1H, m), 2.55-2.60 (3H, m), 4.18 (1H, s), 4.22 (1H,
s), 5.05 (1H, s), 5.10 (1H, s), 6.82 (1/2H, t, J ) 4.9 Hz), 7.17-
7.35 (9H, m), 7.49-7.65 (3H, m), 7.56 (1/2H, t, J ) 5.9 Hz),
7.98-8.03 (2H, m); 13C NMR δ 150.4, 149.7, 137.8, 137.8, 137.4,
134.0, 132.1, 132.1, 131.8, 131.7, 129.0, 128.9, 128.9, 128.6,
128.4, 128.2, 127.9, 127.8, 127.7, 127.4, 127.4, 126.3, 124.1,
P r ep a r a tion of (E)-7-[2-[3-(P h en ylsu lfon yl)-1-p r op yn -
yl]p h en yl]h ep t -2-en -6-yn -1-ol (87). Methyl (E)-7-[2-[3-
(phenylthio)-1-propynyl]phenyl]hept-2-en-6-ynoate (0.186 g,

626 J . Org. Chem., Vol. 62, No. 3, 1997
Grissom et al.
124.1, 93.0, 92.7, 86.3, 86.2, 80.3, 80.2, 79.9, 79.9, 75.8, 75.6,
triethylamine (0.145 mL, 0.106 g, 1.04 mmol) to provide 0.055
g (72%) of 2,3-dihydro-4-[(phenylsulfonyl)methyl]-1H-benz[e]-
indene-1-acetonitrile (91) as a colorless solid: TLC Rf 0.47 (1:1
hexanes/ethyl acetate); IR (Nujol) ν 3061, 2945, 2872, 2253,
1319, 1154 cm-1; 1H NMR δ 2.17 (1H, m), 2.26-2.40 (1H, m),
2.34 (1H, dd, J ) 16.9, 9.7 Hz), 2.72 (1H, dd, J ) 16.9, 3.7
Hz), 2.77-2.87 (2H, m), 3.99 (1H, m), 4.43 (1H, A of AB q, J
) 13.9 Hz), 4.45 (1H, B of AB q, J ) 13.9 Hz), 7.39-7.47 (3H,
m), 7.51 (1H, s), 7.54 (1H, m), 7.62 (1H, m), 7.61-7.64 (2H,
m), 7.71 (1H, d, J ) 8.8 Hz), 7.76 (1H, d, J ) 8.1 Hz); 13C NMR
δ 141.3, 139.5, 138.1, 133.9, 133.0, 131.7, 129.2, 129.1, 129.0,
128.7, 127.5, 125.7, 123.0, 122.7, 118.9, 60.7, 40.8, 30.4, 29.8,
22.2; HRMS (EI) calcd for C22H19NO2S (M+) 361.1137, found
361.1137.
49.4, 49.4, 28.5, 24.9, 17.4, 16.6; HRMS (EI) calcd for C27H23
-
NO3S (M+) 441.1399, found 441.1389.
Gen er a l P r oced u r e for th e Ta n d em En yn e Allen e-
Ra d ica l Cycliza tion of th e En ed iyn e Su lfon es 84-88. A
stirred solution of the respective enediyne sulfone (approxi-
mately 0.2 mmol) in anhydrous benzene (5.35 mL) in a
pressure vial was degassed with dry nitrogen for 30 min. Then
triethylamine (5.0 equiv) and 1,4-CHD (2.649 mL, 2.244 g,
28.00 mmol, c ) 3.5 M) were added via syringe and the vial
was sealed with a Teflon screw cap. The reaction mixture was
heated at 37 °C for 16 h. The volatile components were
removed in vacuo, and the residue was passed through a short
silica gel column with a 1:1 (1:3 for 92) mixture of hexanes/
ethyl acetate. Products 89-93 were obtained after the respec-
tive crude product was subjected to radial chromatography
with an 85:15 (65:35 for 92) mixture of hexanes/ethyl acetate.
Ta n d em En yn e Allen e-Ra d ica l Cycliza tion of Meth yl
(E)-7-[2-[3-(P h en ylsu lfon yl)-1-p r op yn yl]p h en yl]h ep t -2-
en -6-yn oa te (84). The reaction was performed according to
the general procedure for the tandem enyne allene-radical
cyclization using 84 (0.070 g, 0.18 mmol) and triethylamine
(0.124 mL, 0.090 g, 0.89 mmol) to provide 0.0535 g (76%) of
methyl 2,3-dihydro-4-[(phenylsulfonyl)methyl]-1H-benz[e]in-
dene-1-acetate (89) as a yellow oil: TLC Rf 0.52 (1:1 hexanes/
Ta n d em En yn e Allen e-Ra d ica l Cycliza tion of (E)-7-
[2-[3-(P h en ylsu lfon yl)-1-p r op yn yl]p h en yl]h ep t -2-en -6-
yn -1-ol (87). The reaction was performed according to the
general procedure for the tandem enyne allene-radical cy-
clization using 87 (0.069 g, 0.19 mmol) and triethylamine
(0.132 mL, 0.096 g, 0.95 mmol) to provide 0.047 g (68%) of
2,3-dihydro-4-[(phenylsulfonyl)methyl]-1H-benz[e]indene-1-
ethanol (92) as a yellow oil: TLC Rf 0.37 (1:2 hexanes/ethyl
acetate); IR (neat) ν 3420 (br), 3061, 2932, 2886, 1308, 1152
cm-1; 1H NMR δ 1.49 (1H, s, br), 1.59 (1H, m), 1.87-1.98 (2H,
m), 2.04-2.17 (1H, m), 2.65 (2H, dd, J ) 9.8, 4.5 Hz), 3.72
(2H, dd, J ) 7.5, 5.7 Hz), 3.77 (1H, m), 4.45 (2H, s), 7.36-7.42
(3H, m), 7.45-7.51 (1H, m), 7.47 (1H, s), 7.55-7.61 (3H, m),
7.73 (1H, d, J ) 8.1 Hz), 7.83 (1H, d, J ) 8.3 Hz); 13C NMR δ
143.6, 140.6, 138.1, 133.7, 132.9, 130.2, 129.7, 128.9, 128.8,
126.7, 125.3, 124.0, 122.6, 61.6, 60.8, 40.3, 36.9, 30.2, 30.1;
HRMS (EI) calcd for C22H22O3S (M+) 366.1290, found 366.1312.
Ta n d em E n yn e Allen e-R a d ica l Cycliza t ion of N-
(P h en ylm et h oxy)-5-[2-[3-(p h en ylsu lfon yl)-1-p r op yn yl]-
p h en yl]p en t-4-yn -1-im in e (88). The reaction was performed
according to the general procedure for the tandem enyne
allene-radical cyclization using 88 (0.081 g, 0.18 mmol) and
triethylamine (0.128 mL, 0.093 g, 0.92 mmol) to provide 0.058
g (71%) of 2,3-dihydro-N-(phenylmethoxy)-4-[(phenylsulfonyl)-
methyl]-1H-benz[e]inden-1-amine (93) as a pale yellow oil:
TLC Rf 0.47 (1:1 hexanes/ethyl acetate); IR (neat) ν 3258, 3063,
3032, 2928, 2859, 1317, 1152 cm-1; 1H NMR δ 2.04-2.17 (1H,
m), 2.26-2.33 (1H, m), 2.58-2.66 (1H, m), 2.72-2.83 (1H, m),
4.40 (1H, A of AB q, J ) 14.0 Hz), 4.44 (1H, B of AB q, J )
14.0 Hz), 4.61 (1H, A of AB q, J ) 11.6 Hz), 4.64 (1H, B of AB
q, J ) 11.6 Hz), 5.00 (1H, d, J ) 6.6 Hz), 5.45 (1H, s, br), 7.28-
7.43 (8H, m), 7.47 (1H, ddd, J ) 8.3, 6.8, 1.2 Hz), 7.51 (1H, s),
7.54-7.59 (3H, m), 7.71 (1H, d, J ) 8.4 Hz), 7.88 (1H, d, J )
8.3 Hz); 13C NMR δ 143.2, 138.0, 138.0, 136.9, 133.8, 132.8,
132.0, 130.5, 128.9, 128.8, 128.6, 128.5, 128.3, 127.8, 127.1,
125.5, 124.2, 122.7, 65.3, 60.6, 29.8, 29.6; HRMS (EI) calcd for
C27H25NO3S (M+) 443.1555, found 443.1552.
ethyl acetate); IR (neat) ν 3057, 2947, 1730, 1319, 1152 cm-1
;
1H NMR δ 1.94 (1H, m), 2.16 (1H, m), 2.21 (1H, dd, J ) 15.4,
11.0 Hz), 2.61-2.70 (3H, m), 3.69 (3H, s), 4.06 (1H, ddd, J )
11.1, 8.0, 3.2 Hz), 4.44 (2H, s), 7.37-7.44 (3H, m), 7.50 (1H,
m), 7.51 (1H, s), 7.57-7.63 (3H, m), 7.77 (2H, t, J ) 8.5 Hz);
13C NMR δ 173.0, 141.8, 140.9, 138.1, 133.8, 132.9, 130.7,
129.3, 128.9, 128.9, 128.8, 127.0, 125.4, 123.5, 122.7, 60.8, 51.7,
40.5, 38.3, 30.6, 29.6; HRMS (EI) calcd for C23H22O4S (M+)
394.1239, found 394.1244.
Ta n d em En yn e Allen e-Ra d ica l Cycliza tion of Meth yl
(E)-7-[2-[3-(p h en ylsu lfon yl)-1-p r op yn yl]p h en yl]-3-m eth -
ylh ep t-2-en -6-yn oa te (85). The reaction was performed
according to the general procedure for the tandem enyne
allene-radical cyclization using 85 (0.077 g, 0.19 mmol) and
triethylamine (0.132 mL, 0.096 g, 0.95 mmol) to provide 0.060
g (78%) of methyl 2,3-dihydro-R-methyl-4-[(phenylsulfonyl)-
methyl]-1H-benz[e]indene-1-acetate (90) as a yellow oil (3.5:1
mixture of diastereomers): TLC Rf 0.57 (1:2 hexanes/ethyl
acetate); IR (neat) ν 3063, 2951, 2854, 1727, 1318, 1154 cm-1
;
1H NMR major diastereoisomer d 1.13 (3H, d, J ) 7.1 Hz),
2.05-2.16 (2H, m), 2.58-2.85 (3H, m), 3.53 (3H, s), 3.88 (1H,
m), 4.43 (2H, s), 7.36-7.44 (3H, m), 7.48 (1H, ddd, J ) 8.3,
6.8, 1.5 Hz), 7.55-7.63 (4H, m), 7.70 (1H, d, J ) 8.1 Hz), 7.80
(1H, d, J ) 8.4 Hz); 1H NMR minor diastereoisomer δ 0.68
(3H, d, J ) 7.1 Hz), 2.05-2.16 (2H, m), 2.58-2.85 (2H, m),
3.09 (1H, m), 3.68 (3H, s), 4.20 (1H, m), 4.45 (2H, s), 7.36-
7.44 (3H, m), 7.51 (1H, s), 7.55 (1H, m), 7.55-7.63 (3H, m),
7.75 (1H, d, J ) 8.1 Hz), 7.84 (1H, d, J ) 8.4 Hz); 13C NMR
(major diastereoisomer) δ 176.1, 141.9, 141.4, 138.1, 133.7,
132.7, 130.7, 130.6, 128.9, 128.7, 128.7, 126.6, 125.2, 125.0,
122.6, 60.7, 51.7, 47.1, 43.3, 30.3, 29.7, 16.8; HRMS (EI) calcd
for C24H24O4S (M+) 408.1396, found 408.1387.
Ack n ow led gm en t. We gratefully acknowledge fi-
nancial support from the University of Utah and the
National Institutes of Health (GM 49991-01).
Su p p or tin g In for m a tion Ava ila ble: NMR spectra of all
new compounds (89 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
Ta n d em En yn e Allen e-Ra d ica l Cycliza tion of (E)-7-
[2-[3-(P h en ylsu lfon yl)-1-p r op yn yl]p h en yl]h ep t -2-en -6-
yn en itr ile/(Z)-7-[2-(3-(P h en ylsu lfon yl)-1-pr opyn yl)ph en yl]-
h ep t-2-en -6-yn en itr ile (86). The reaction was performed
according to the general procedure for the tandem enyne
allene-radical cyclization using 86 (0.075 g, 0.21 mmol) and
J O961049J