Synthesis of bicyclic enediynes from bis[phenyl[trifluoromethanesulfonyl)oxy]iodo]acetylene: A tandem Diels-Alder/palladium(II)- and copper(I)cocatalyzed cross-coupling approach

Article abstract of DOI:10.1021/jo960750k

The reaction of bicycloalkenylbis(phenyliodonium) triflates 1a or b (available via the Diels-Alder reaction of bis[phenyl[(trifluoromethanesulfonyl)oxy]iodo]acetylene with cyclopentadiene or furan, respectively) with alkynylstannanes 2a-g at room temperature in DMF in the presence of catalytic amounts of trans-benzyl(chloro)bis(triphenylphosphine)palladium(II) and copper(I) iodide proceeds smoothly and with selectivity to afford good to excellent yields of bicyclic enediynes 3a-k.

Full text of DOI:10.1021/jo960750k

6
162
J . Org. Chem. 1996, 61, 6162-6165
Syn th esis of Bicyclic En ed iyn es fr om
Bis[p h en yl[(tr iflu or om eth a n esu lfon yl)oxy]iod o]a cetylen e: A
Ta n d em Diels-Ald er /P a lla d iu m (II)- a n d Cop p er (I)-Coca ta lyzed
Cr oss-Cou p lin g Ap p r oa ch
J ohn H. Ryan and Peter J . Stang*
Department of Chemistry, The University of Utah, Salt Lake City, Utah 84112
Received April 24, 1996X
The reaction of bicycloalkenylbis(phenyliodonium) triflates 1a or b (available via the Diels-Alder
reaction of bis[phenyl[(trifluoromethanesulfonyl)oxy]iodo]acetylene with cyclopentadiene or furan,
respectively) with alkynylstannanes 2a -g at room temperature in DMF in the presence of catalytic
amounts of trans-benzyl(chloro)bis(triphenylphosphine)palladium(II) and copper(I) iodide proceeds
smoothly and with selectivity to afford good to excellent yields of bicyclic enediynes 3a -k .
In tr od u ction
The discovery of new potent antitumor antibiotics, such
nanes, or alkynylzinc reagents.11,12 These procedures are
usually performed in polar solvents (e.g., DMF or THF)
at elevated temperatures over a period of 1-8 h and
generally proceed in good yields (with retention of diha-
loalkene stereochemistry). Unfortunately, few of these
methods allow for the installation of substituents (e.g.,
as calicheamicins, esperamicins, dynemicin, and more
recently, the kedarcidin and C-1027 chromophores, which
contain cis-enediynes, has sparked renewed interest in
the chemistry of enediynes with both open chain and
8
d
a carbocyclic framework) on the olefin of the enediyne.
1
cyclic structures. It is widely recognized that Bergman
Furthermore, few examples of coupling with unprotected
alkynes bearing an electron-withdrawing functionality,
such as a carbonyl group, have appeared.
2
cyclization sthe cycloaromatization of conjugated cis-
enediynes to 1,4-benzenoid diradicalsswithin these com-
pounds is responsible for their biological activity.3 Fur-
thermore, conjugated cis-enediynes are useful starting
materials in the synthesis of various carbocyclic com-
In recent years, a great variety of stable, crystalline
alkenyl(phenyl)iodonium salts have become readily avail-
able and are employed as versatile intermediates in
chemical synthesis.13 They undergo a large number of
carbon-carbon bond-forming reactions by nucleophilic
substitution of the iodobenzene moiety with organocu-
4
pounds such as tetrahydronaphthalenes, naphthoquino-
5
6
7
nes, dihydroindene, and dihydrobenzindene systems.
A number of interesting strategies have been recently
developed for the direct construction of hex-3-ene-1,5-
diyne systems that involve installation of the ene part
1
4
14
prates and soft enolates and by palladium-catalyzed
carbonylation1 and coupling of alkenyl(phenyl)iodonium
salts with olefins.15 More recently, we exploited the
electron-deficient character of these iodonium compounds
in a palladium(II)- and copper(I)-cocatalyzed coupling of
stereodefined alkenyl(phenyl)iodonium triflates with un-
saturated tri-n-butylstannanes.16 A variety of stannanes,
including alkenylstannanes and simple and functional-
4a
8
of cis-enediynes as the final step; however, the more
traditional and common syntheses involve metal-cata-
9
lyzed cross-coupling of halo enynes, 1,2-dihaloalkenes,
1
0
and 1,2-dihalobenzenes with alkynes, alkynylstan-
X
Abstract published in Advance ACS Abstracts, August 1, 1996.
(1) For recent reviews: (a) Danishefsky, S. J .; Shair, M. D. J . Org.
Chem. 1996, 61, 16. (b) Nicoloau, K. C.; Smith, A. L. in Modern
Acetylene Chemistry; Stang, P. J ., Diederich, F., Eds.; VCH: Weinheim,
1
3
995; Chapter 7. (b) Nicolaou, K. C. Angew. Chem., Int. Ed. Engl. 1993,
2, 1377. (c) Pratveil, G.; Bernardou, J .; Meunier, B. Angew. Chem.,
(10) (a) Singh, R.; J ust, G. J . Org. Chem. 1989, 54, 4453. (b) Singh,
R.; J ust, G. Tetrahedron Lett. 1987, 28, 5981.
Int. Ed. Engl. 1995, 34, 746. (d) Magnus, P. Tetrahedron 1994, 50,
397. Part of Tetrahedron’s Symposia-in-print No. 53. Doyle, T. W.,
(11) For more traditonal procedures: (a) Duch eˆ ne, K.-H.; V o¨ gtle,
F. Synthesis 1986, 654. (b) Takahashi, S.; Kuroyama, Y.; Sonogashira,
K; Hagihara, N. Synthesis 1980, 627. (c) Sonogashira, K.; Tohda, Y.;
Hagihara, N. Tetrahedron Lett. 1975, 4467. (d) Review: Trost, B. M.
Tetrahedron 1977, 33, 2615. (e) Tsuji, J . Organic Synthesis with
Palladium Compounds; Springer-Verlag: New York, 1980.
(12) For recent examples that deal with the introduction of novel
acetylenic side chains: (a) K o¨ nig, B.; R u¨ tters, H. Tetrahedron Lett.
1994, 35, 3501. (b) Alami, M.; Crousse, B.; Linstrumelle, G. Tetrahe-
dron Lett. 1994, 35, 3543. (c) McGaffin, G.; de Meijere, A. Synthesis
1994, 583. (d) Stracker, E. C.; Zweifel, G. Tetrahedron Lett. 1991, 32,
3329. (e) Magriotis, P. A.; Scott, M. E.; Kim, K. D. Tetrahedron Lett.
1991, 32, 6085.
(13) Reviews: (a) Stang, P. J .; Zhdankin, V. V. Chem. Rev., in press.
(b) Koser, G. F. In The Chemistry of Halides, Pseudo-Halides and
Azides, Suppl. D2; Patai, S., Rappoport, Z., Eds.; Wiley-Interscience:
Chichester, 1995; Chapter 21, pp 1173-1274. (c) Varvoglis, A. The
Organic Chemistry of Polycoordinated Iodine; VCH Publishers: New
York, 1992.
1
Kadow, J . F., Eds.; Tetrahedron 1994, 50, 1311-1538. (e) Thebtara-
nonth, C.; Thebtaranonth, Y. Cyclization Reactions; CRC: Boca Raton,
FL, 1994; pp 346-357.
(2) (a) Bergman, R. G. Acc. Chem. Res. 1973, 6, 25. For other early
observations of the cyclization of enediynes see: (b) Mayer, J .;
Sondheimer, F. J . Am. Chem. Soc. 1966, 88, 603. (c) Darby, N.; Kim,
C. U.; Sala u¨ n, J . A.; Shelton, K. W.; Takada, S.; Masamune, S. J . Chem.
Soc., Chem. Commun. 1971, 1516.
(
3) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed. Engl. 1991,
3
0, 1387.
(
(
4) Magriotis, P. A.; Kim, K. D. J . Am. Chem. Soc. 1993, 115, 2972.
5) Grissom, J . W.; Gunawardena, G. U. Tetrahedron Lett. 1995, 36,
4
951.
(6) Grissom, J . W.; Huang, D. Angew. Chem., Int. Ed. Engl. 1995,
3
4, 2037 and references therein.
(
7) Grissom, J . W.; Klingberg, D. Tetrahedron Lett. 1995, 36, 6607
and references therein.
8) (a) Shibuya, M.; Sakai, Y.; Naoe, Y. Tetrahedron Lett. 1995, 36,
97. (b) J ones, G. B.; Huber, R. S.; Mathews, J . E. J . Chem. Soc., Chem.
Commun. 1995, 1791. (c) Nuss, J . M., Murphy, M. M. Tetrahedron Lett.
(
(14) (a) Ochiai, M.; Sumi, K.; Takaoka, Y.; Kunishima, M.; Nagao,
Y.; Shiro, M.; Fujita, E. Tetrahedron 1988, 44, 4095. (b) Ochiai, M.;
Sumi, K.; Nagao, Y.; Fujita, E. Tetrahedron Lett. 1985, 26, 2351.
(15) (a) Kurihara, Y.; Sodoeka, M.; Shibasaki, M. Chem. Pharm.
Bull. 1994, 42, 2357. (b) Moriarty, R. M.; Epa, W. R.; Awasthi, A. K.
J . Am. Chem. Soc. 1991, 113, 6315. (c) Ochiai, M.; Takaoka, Y.; Nagao,
Y. J . Am. Chem. Soc. 1988, 110, 6565.
8
1
1
1
994, 35, 37. (d) Hopf, H.; Theurig, M. Angew. Chem., Int. Ed. Engl.
994, 33, 1099. (e) Wang, K. K.; Wang, Z.; Gu, Y. G. Tetrahedron Lett.
993, 34, 8391.
(9) (a) Myers, A. G.; Harrison, P. M.; Kuo, E. Y. J . Am. Chem. Soc.
1
991, 113, 694. (b) Magnus, P.; Lewis, R. T.; Huffman, J . C. J . Am.
(16) Hinkle, R. J .; Poulter, G. T.; Stang, P. J . J . Am. Chem. Soc.
1993, 115, 11626.
Chem. Soc. 1988, 110, 6921.
S0022-3263(96)00750-5 CCC: $12.00 © 1996 American Chemical Society

Synthesis of Bicyclic Enediynes
J . Org. Chem., Vol. 61, No. 18, 1996 6163
ized alkynylstannanes, couple in good yields under
exceedingly mild conditions and afford stereodefined
products (eq 1).
Ta ble 1. P a lla d iu m (II)/Cop p er (I)-Coca ta lyzed Cou p lin g
of Alk en ylbis(p h en yliod on iu m ) Bistr ifla tes 1a ,b w ith
Alk yn ylsta n n a n es 2a -g
diiodonium
salt
alkynyl-
stannane
yielda
product (%)
entry
X
R
1
2
3
4
5
6
7
8
9
1a
1a
1b
1a
1b
1a
1b
1a
1b
1a
1a
CH2
CH2
O
CH2
O
CH2
O
CH2
O
2a
2b
2b
2c
2c
2d
2d
2e
2e
2f
CH3
nBu
nBu
SiMe3
SiMe3
3a
3b
3c
3d
3e
3f
3g
3h
3i
82
76
55
60
63
92
54
77
53
52
86
In 1991, we reported a general approach to the
synthesis of bicycloalkenylbis(phenyliodonium) bistri-
flates 1 by the Diels-Alder reaction of bis(phenyliodonio)-
Ph
Ph
(CO)N(CH2)5
(CO)N(CH )
(CO) Bu
(CO)C10H15
1
7
acetylene bistriflate with dienes such as cyclopentadi-
2
5
ene and furan (eq 2).1 This new class of alkenyl
7a
t
10
1
CH2
CH2
3j
3k
1
2g
a
Isolated yields of pure compounds based on the starting
diiodonium salts.
DMF at room temperature results in rapid formation of
the desired enediynes in good to excellent yields (eq 4,
1
Table 1). H NMR and analytical TLC analyses of the
crude reaction products indicated that clean coupling had
occurred; the major components were iodobenzene, the
enediyne 3, and small amounts of the starting tributyltin
acetylene (even after KF treatment). Importantly, com-
petitive coupling of iodobenzene (produced as a byproduct
of the reaction) with the alkynylstannanes occurs to less
than 5%, which is in accord with our earlier observations
diiodonium salts undergoes reaction with a range of
1
8
nucleophiles in the presence of copper(I) salts, and in
almost all cases, the products observed are those result-
ing from vinylic nucleophilic substitution of the iodoben-
zene moiety. In particular, the coupling reaction of the
bicycloalkenyldiiodonium salts with simple lithium-
alkynyl cuprates results in selective nucleophilic substi-
1
6
associated with alkenyl(phenyliodonium) triflates. How-
ever longer reaction times do result in the formation of
varying amounts (10-20%) of such undesired, coupled
products. Both the palladium(II) and copper(I) catalysts
are necessary for the reaction to occur. The lower yields
observed for the 3,5-epoxy-1,4-cyclohexadienes 3c,e,g,i,j
are thought to be due to their instability in the reaction
mixtures. Indeed, the ratios of iodobenzene to enediyne
in the crude reaction products were much lower than the
tution of the two iodobenzene groups with the alkynes
8b
(
eq 3).1 These reactions occur under mild conditions
to afford the respective bicyclic enediynes substituted by
alkyl, trimethylsilyl, or aryl groups; however, in some
cases the yields are only moderate. This methodology is
also restricted to using those alkynes that will form stable
alkynyl cuprates. In contrast, a wide variety of alkynyl-
stannanes are known,19 including those substituted by
electron-withdrawing groups. In this paper, we report
that the palladium(II) and copper(I) cocatalyzed double
coupling reaction of alkenyl bis(phenyliodonium)triflates
with a variety of alkynylstannanes proceeds under mild
conditions to give good to excellent yields of bicyclic
enediynes, including those with functionalized substit-
uents.
1
expected 2:1, as determined by H NMR analyses.
Analytically pure enediynes 3 were isolated as viscous
yellow oils by column or radial chromatography, on silica
gel. Those containing electron-withdrawing substituents
3h -k were markedly less stable than the alkyl-, (tri-
methylsilyl)-, and aryl-substituted compounds; however,
all could be stored for weeks, as dilute solutions, at -20
°
C with only minimal deterioration.
Resu lts a n d Discu ssion
The products were identified by the IR, UV, NMR and
high-resolution mass spectral data and in the cases of
Reaction of the bicycloalkenylbis(phenyliodonio) bis-
triflates 117 with alkynylstannanes 2 in the presence
of 5 mol % of trans-benzyl(chloro)bis(triphenylphosphine)-
palladium(II)20 and 8 mol % of copper iodide in degassed
b-f agreed closely with literature data.1
8b
The IR
3
19
spectra all show the triple bond absorption at 2215-2125
-1
cm . Frequently, these bands resolved into two separate
absorptions, a phenomenon also observed in the case of
2
1
the parent cis-hex-3-ene-1,5-diyne and expected with
compounds of such symmetry.22 The UV spectra all
contain an absorption maximum between 284 and 364
nm. As expected, the λmax increases with extent of
(
17) (a) Stang, P. J .; Zhdankin, V. V. J . Am. Chem. Soc. 1991, 113,
4
6
571.(b) Stang, P. J .; Zhdankin, V. V. J . Am. Chem. Soc. 1990, 112,
437.
(
18) (a) Stang, P. J .; Schwarz, A.; Blume, T.; Zhdankin, V. V.
Tetrahedron Lett. 1992, 33, 6759. (b) Stang, P. J .; Blume, T.; Zhdankin,
V. V. Synthesis 1993, 35.
(
19) (a) Cauletti, C.; Furlani, C.; Sebald, A. Gazz. Chim. Ital. 1988,
(21) Okamura, W. H.; Sondheimer, F. J . Am. Chem. Soc. 1967, 89,
1
7
18, 1. (b) Kleiner, F. G.; Neumann, W. P. Leibigs Ann. Chem. 1968,
16, 19. (c) Davidsohn, W. E.; Henry, M. C. Chem. Rev. 1967, 67, 73.
5991.
(22) Eliel, E. N.; Wilen, S. H.; Mander, L. N. Stereochemistry of
(
20) Fitton, P.; McKeon, J . E.; Beam, B. C. J . Chem. Soc., Chem.
Organic Compounds; Wiley-Interscience: New York, 1994; Chapter
4.
Commun. 1969, 370.

6
164 J . Org. Chem., Vol. 61, No. 18, 1996
Ryan and Stang
conjugation and polarization of the enediyne system in
order of alkyl < trimethylsilyl < amido < carbonyl <
phenyl.23 In addition, for any given R group, the λmax for
the oxy-bridged analogues is 10-15 nm greater than the
tion of one of the propargyl positions of an enediyne, by
an electron-withdrawing group, such as a carbonyl,
causes an increase in the rate of Bergman cyclization.
26
In conclusion, we have developed a two-step synthesis
of functionalized bicyclic enediynes starting from bis-
(phenyliodonio)acetylene bistriflate utilizing a tandem
Diels-Alder/metal-catalyzed cross-coupling approach.
The second step, the focus of this paper, is the first
example of a 2-fold, metal-catalyzed, cross-coupling reac-
tion of alkenyldiiodonium salts and illustrates the emer-
gence of such compounds as useful synthons for bifunc-
tional electrophilic alkenes. In contrast to the great
variety of nucleophiles available for metal-catalyzed
cross-coupling reactions, only a few types of biselectro-
corresponding methylene-bridged compounds. The 1
H
NMR spectra display patterns indicative of 1,2-disubsti-
tuted norbornadienes24 or 3,5-epoxy-1,4-cyclohexadienes
along with the corresponding signals of the alkynyl R
groups. For 3a ,b,d ,f,h ,j,k , the olefinic protons are found
at 6.90-6.78 ppm, the allylic bridgehead protons at 3.84-
3
.53 ppm, and the geminally-coupled (J ∼ 7 Hz), bridging,
methylene protons at 2.33-2.05 ppm. Similarly, for
c,e,g,i, the olefinic protons resonate at 7.21-7.10 ppm
3
and the allylic, bridgehead protons at 5.58-5.33 ppm.
Particularly characteristic in the 13C NMR spectra are
the signals due to the acetylenic carbons at 76-114 ppm
and olefinic carbons at 140-143 ppm. For 3a ,b,d ,f,h ,j,k ,
the signals at ca. 56 ppm and ca. 72 ppm are due to the
bridgehead-methine and bridging-methylene carbons,
respectively, whereas for 3c,e,g,i, the oxygenated, bridge-
head methine is found at 87 ppm. The mass spectra
afford, in most cases, the appropriate molecular ions. For
compounds 3j and 3k , no molecular ion was observed
under a variety of conditions; however, the fragmentation
pattern and all other spectroscopic data are in accord
with the proposed structures. For compounds 3a ,c,f,g,
an interesting fragmentation takes place under EI condi-
11
philes (e.g, dihaloalkenes and benzenes) are available.
The stable alkenyldiiodonium salts can be thought of as
new, highly reactive members of this select group of
bifunctional electrophilic alkenes.
Exp er im en ta l Section
Gen er a l Meth od s. Reactions were generally performed in
flame-dried glassware under an atmosphere of argon, using
anhydrous solvents. DMF was distilled under reduced pres-
sure from CaH
2
, stored over 4 Å molecular sieves, and purged
with argon for 15 min before use. Starting diiodonium salts
17b
1
a ,b were prepared according to the known procedure and
dried for 2 h under vacuum prior to use. Alkynylstannanes
tions; the molecular ion loses C
a retro Diels-Alder reaction (eq 5).
4
H
4
X, presumably due to
2a -g were prepared according to known methods from the
2
5
19a,27
corresponding terminal acetylenes.
Analytical thin layer
chromatography (TLC) was conducted on aluminum-backed
UV254 TLC plates. Column chromatography was performed
2
8
in the usual manner using silica gel (230-400 mesh). Radial
chromatography (silica gel, 200-400 mesh) was performed
with a Harrison Research chromatotron, Model 7924T. In-
frared spectra were recorded using neat samples on NaCl
plates. UV spectra were recorded as dilute solutions in a 1
1
3
cm pathlength cell. Proton and C NMR spectra were
measured in CDCl at 300 and 75 MHz, respectively, and were
calibrated against internal standards (residual CHCl (7.27
(77.23 ppm)
3
3
1
ppm) for H NMR and the central peak of CDCl
3
for 13C NMR). Mass spectra were obtained under electron
impact (EI) conditions at 70 eV, and perfluorokerosine was
used as a reference for peak-matching.
The yields of bicyclic enediynes using the palladium-
II)- and copper(I)-cocatalyzed double coupling of bicyclic
(
alkenylbis(phenyliodonium) bistriflates with alkynyl-
stannanes are generally higher than those observed for
the corresponding coupling reaction with lithium alkynyl-
cuprates.1 More importantly, the current work allows
for the formation and isolation of the sensitive, function-
alized enediynes, such as 3i and 3k . Little is known about
Gen er a l P r oced u r e for t h e P r ep a r a t ion of Bicyclic
En ed iyn es. To degassed DMF (2.5-5 mL) at room temper-
ature under an atmosphere of argon was added diiodonoium
salt 1 (0.5-1.0 mmol) followed by alkynylstannane 2 (1.2-
2.4 mmol), trans-benzyl(chloro)bis(triphenylphosphine)pal-
ladium(II) (5 mol %), 0.025-0.050 mmol), and copper iodide
8b
(
8 mol %, 0.04-0.08 mmol). After the mixture had stirred at
rt for 30 min it was worked up as follows: The reaction
mixture was poured into saturated NH
Cl (20 mL) and
4
extracted with ether (3 × 10 mL). The combined ether extracts
were stirred vigorously with KF (10% aqueous, 10 mL) for 15
min, the mixture was filtered to remove precipitated Bu
and then the phases were separated. The organic phase was
), filtered, and
3
SnF,
washed with water (3 × 10 mL), dried (MgSO
4
concentrated to give the crude product, which was subjected
to chromatographic purification.
2
,3-Di-1′-pr opyn ylbicyclo[2.2.1]h epta-2,5-dien e (3a). The
reaction of diiodonium 1a (796 mg, 1.00 mmol) with alkynyl-
stannane 2a (823 mg, 2.4 mmol) under the usual conditions
gave an orange oil that was subjected to column chromatog-
such compounds in terms of their properties and reactiv-
ity (e.g., Bergman cyclization) since these species would
be difficult to obtain via more traditional methods, e.g.,
the coupling of dihaloalkenes, which require, amongst
other things, elevated temperatures. Such compounds
are of interest because it has been shown that substitu-
raphy (hexanes). Concentration of the fractions (R
afforded 3a (138 mg, 82%) as a light yellow oil: H NMR δ
f
0.20)
1
6.79 (dd, J ) 1.9, 1.9 Hz, 2H), 3.57-3.54 (m, 2H), 2.15 (dt, J
) 6.5, 1.5 Hz, 1H), 2.11 (s, 6H), 2.04 (dt, J ) 6.5, 1.6 Hz, 1H);
(
23) Rao, C. N. R. Ultra Violet and Visible Spectroscopy; Chemical
Applications, 3rd ed.; Butterworths: London, 1975.
24) Abraham, R. J .; Loftus, P. Proton and Carbon-13 NMR Spec-
troscopy; An Integrated Approach; Heyden: London, 1978.
25) Silverstein, R. M.; Bassler, G. C.; Morrill, T. C. Spectrometric
Identification of Organic Compounds, 4th ed.; Wiley: New York, 1981.
(26) Semmelhack, M. F.; Neu, T.; Foubelo, F. J . Org. Chem. 1994,
59, 5038.
(27) Brandsma, L. Preparative Acetylenic Chemistry; Elsevier: Am-
sterdam, The Netherlands, 1971. Williamson, B. L.; Stang, P. J .; Arif,
A. M. J . Am. Chem. Soc. 1993, 115, 2590 and references therein.
(28) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(
(

Synthesis of Bicyclic Enediynes
J . Org. Chem., Vol. 61, No. 18, 1996 6165
1
3
7.21 (dd, J ) 1.0, 1.0 Hz, 2H), 5.58 (dd, J ) 1.0 Hz, 2H); 13
C
C NMR δ 142.0, 140.4, 98.9, 76.3, 71.6, 56.1, 5.6; IR νmax 3080,
2
(
993, 2931, 2866, 2209, 1448, 1375, 1297 cm-1; UV-vis λmax
log ꢀ, chloroform) 284 (3.7) nm; MS 168 (100), 102 (49); HRMS
NMR δ 143.2, 141.2, 131.7, 129.0, 128.6, 123.1, 106.9, 86.9,
83.6; IR νmax 3061, 3024, 2931, 2194, 2172, 1596, 1484, 1443,
-1
calcd for C13
H
12 168.0939, found 168.0928.
1288, 1273, 1031, 910, 880, 850, 755, 731, 709, 689 cm ; UV-
vis (hexane) λmax (log ꢀ, cyclohexane) 364 (4.7) nm; MS 294
1
8b
2
,3-Di-1′-h exyn ylbicyclo[2.2.1]h ep ta -2,5-d ien e (3b).
The reaction of diiodonium 1a (796 mg, 1.00 mmol) with
alkynylstannane 2a (891 mg, 2.4 mmol) under the usual
conditions gave an orange oil which was subjected to column
(17), 226 (100); HRMS calcd for C22
H
14O 294.1045, found
294.1063; calcd for M - C H O (C18H10) 226.0783, found
4 4
226.0771.
chromatography (hexanes). Concentration of the fractions (R
.25) afforded 3a (190 mg, 76%) as a light yellow oil: 1H NMR
δ 6.79 (dd, J ) 2.0, 2.0 Hz, 2H), 3.57-3.53 (m, 2H), 2.46 (t, J
7.0 Hz, 4H), 2.17 (dt, J ) 6.5, 1.7 Hz, 1H), 2.05 (dt, J ) 6.5,
.6 Hz, 1H), 1.62-1.42 (m, 8H), 0.93 (t, J ) 7.2 Hz, 6H); 13
NMR δ 142.0, 140.6, 103.4, 77.1, 71.6, 56.0, 31.1, 22.2, 20.2,
3.9; IR νmax 3070, 2961, 2932, 2871, 2205, 1466, 1458, 1296
f
2,3-Bis[[(N,N-pen tam eth ylen eam in o)car bon yl]eth yn yl]-
bicyclo[2.2.1]h ep ta -2,5-d ien e (3h ). The reaction of bis
iodonium 1a (798 mg, 1.00 mmol) with alkynylstannane 2e
(1.02g, 2.4 mmol) under the usual conditions gave an orange
oil that was subjected to column chromatography (1:1 ethyl
0
)
1
C
f
acetate/hexanes). Concentration of the fractions (R 0.3)
afforded 3h (280 mg, 77%) as an unstable yellow oil: 1H NMR
δ 6.78 (dd, J ) 1.9, 1.9 Hz, 2H), 3.79-3.75 (m, 2H), 3.67 (t, J
) 5.4H), 4H), 3.55 (t, J ) 5.6 Hz, 4H), 2.23 (dt, J ) 6.9, 1.6
1
-
1
cm ; UV-vis λmax (log ꢀ, cyclohexane) 302 (3.7) nm; MS 252
(100); HRMS calcd for C19
H
24 252.1878, found 252.1891.
2
3c).
,3-Di-1′-h exyn yl-7-oxa b icyclo[2.2.1]h ep t a -2,5-d ien e
Hz, 1H), 2.15 (dt, J ) 6.9, 1.6 Hz, 1H), 1.70 -1.48 (m, 12H);
1
8b
13C NMR δ 152.6, 144.4, 141.8, 95.4, 85.3, 72.5, 56.0, 48.4, 42.5,
(
The reaction of diiodonium 1b (399 mg, 0.50 mmol)
with alkynylstannane 2b (446 mg, 1.2 mmol) under the usual
conditions gave an orange oil that was subjected to radial
chromatography (1:40 ethyl acetate/hexanes). Concentration
26.6, 25.6, 24.6; IR νmax 3071, 2981, 2956, 2930, 2869, 2198,
-
1
1623, 1448, 1260, 1213, 1130, 1021, 668 cm ; UV-vis (hex-
anes) λmax (log ꢀ, cyclohexane) 330 (4.0) nm; MS 363 (9), 279
of the fractions (R
f
0.20) afforded 3c (70 mg, 55%) as a light
(28), 86 (63), 84 (100); HRMS calcd for C23
found 363.2090.
26 2 2
H N O 363.2073,
1
yellow oil: H NMR δ 7.10 (dd, J ) 1.1, 1.1 Hz, 2H), 5.33 (dd,
J )1.1, 1.1 Hz, 2H), 2.48 (t, J ) 3.1 Hz, 4H), 1.62-1.41 (m,
2,3-Bis[[(N,N-pen tam eth ylen eam in o)car bon yl]eth yn yl]-
7-oxa bicyclo[2.2.1]h ep ta -2,5-d ien e (3i). The reaction of
diiodonium 1b (399 mg, 0.50 mmol) with alkynylstannane 2e
(511 mg, 1.2 mmol) occurred under the usual conditions except
that the crude black reaction mixture was subjected directly
to column chromatography (ethyl acetate) rather than aqueous
H), 0.94 (t, J ) 7.3 Hz, 6H); 13C NMR δ 143.2, 140.5, 107.4,
6.7, 74.7, 30.9, 22.2, 20.3, 13.9; IR νmax 3017, 2934, 2873, 2215,
8
8
2
203, 1733, 1466, 1273, 1031, 879, 707 cm-1; UV-vis λmax (log
ꢀ
, cyclohexane) 314 (3.5) nm; MS 254 (87), 186 (69), 129 (100);
HRMS calcd for C18
H
22O 254.1671, found 254.1682.
f
workup. Concentration of the fractions (R 0.4) afforded 3i (110
2
,3-Bis[(tr im eth ylsilyl)eth yn yl]bicyclo[2.2.1]h ep ta -2,5-
mg, 53%) as an unstable yellow oil: 1H NMR δ 7.13 (dd, J )
1
8b
d ien e (3d ).
The reaction of diiodonium 1a (796 mg, 1.00
1
4
.1, 1.1 Hz, 2H), 5.56 (dd, J ) 1.1, 1.1 Hz, 2H), 3.71-3.65 (m,
mmol) with alkynylstannane 2c (929 mg, 2.4 mmol) under the
usual conditions gave an orange oil that was subjected to
column chromatography (1:40 ethyl acetate/hexanes). Con-
13
H), 3.60 (dt, J ) 7.7, 5.0 Hz, 4H), 1.71-1.53 (m, 12H);
C
NMR δ 152.2, 144.3, 143.1, 98.9, 86.6, 82.7, 48.5, 42.7, 26.7,
2
1137, 1014, 912, 848, 724 cm ; UV-vis λmax (log ꢀ, chloroform)
5.6, 24.7; IR νmax 2941, 2860, 2199, 2185, 1613, 1434, 1258,
centration of the fractions (R
as a light yellow oil: H NMR δ 6.80 (dd, J ) 1.9, 1.9 Hz, 2H),
f
0.21) afforded 3d (170 mg, 60%)
-1
1
3
40 (3.8); MS 277 (4), 113 (10), 84 (100).
3
6
1
2
λ
.67-3.63 (m, 2H), 2.19 (dt, J ) 6.6, 1.6 Hz, 1H), 2.09 (dt, J )
.6, 1.5 Hz, 1H), 0.22 (s, 18H); 13C NMR δ 143.5, 142.0, 109.1,
00.7, 71.9, 55.9, 0.2; IR νmax 3070, 2997, 2961, 2900, 2871,
2,3-Bis[(ter t-bu tylcar bon yl)eth yn yl]bicyclo[2.2.1]h epta-
,5-d ien e (3j). The reaction of diiodonium 1a (798 mg, 1.00
2
-
1
mmol) with alkynylstannane 2e (958 mg, 2.4 mmol) under the
usual conditions gave a dark brown oil that was subjected to
column chromatography (1:20 ethyl acetate/hexanes). Con-
142, 2127, 1250, 846, 759, 742, 623 cm ; UV-vis (hexanes)
max (log ꢀ, cyclohexane) 314 (4.0) nm; MS 284 (88), 203 (100);
HRMS calcd for C17
H
24Si
2
284.1417, found 284.1397.
f
centration of the fractions (R 0.4) afforded 3j (160 mg, 52%)
2
,3-Bis[(t r im et h ylsilyl)et h yn yl]-7-oxa b icyclo[2.2.1]-
1
1
8b
as an unstable yellow oil: H NMR δ 6.85 (dd, J ) 1.9, 1.9
h ep ta -2,5-d ien e (3e).
The reaction of diiodonium 1b (399
Hz, 2H), 3.86-3.82 (m, 2H), 2.31 (dt, J ) 6.9, 1.6 Hz, 1H),
mg, 0.50 mmol) with alkynylstannane 2c (465 mg, 1.2 mmol)
under the usual conditions gave an orange oil that was
2
1
2
.22 (dt, J ) 6.9, 1.5 Hz, 1H), 1.24 (s, 18H); 13C NMR δ 194.1,
45.9, 142.0, 100.3, 86.4, 72.6, 56.6, 45.1, 26.3; IR νmax 2968,
957, 2187, 2170, 1655, 1478, 1458, 1171, 1084, 1066, 1045,
subjected to radial chromatography (1:1 CH
2 2
Cl /hexanes).
Concentration of the fractions (R 0.35) afforded 3e (90 mg,
f
-
1
1
1017, 1002, 703 cm ; UV-vis λmax (log ꢀ, hexanes) 338 (3.7)
nm; MS 308 (36), 280 (36), 252 (46), 223 (74), 196 (39), 181
6
3%) as a light yellow oil: H NMR δ 7.11 (dd, J ) 1.0, 1.0
13
Hz, 2H), 5.42 (dd, J ) 1.1, 1.0 Hz, 2H), 0.24 (s, 18H); C NMR
(
33), 167 (37), 157 (33), 69 (61), 57 (100); HRMS calcd for
308.1776. Found 308.1777.
,3-Bis[(a d a m a n t ylca r b on yl)e t h yn yl]b icyclo[2.2.1]-
h ep ta -2,5-d ien e (3k ). The reaction of diiodonium 1a (798 mg,
.00 mmol) with alkynylstannane 2e (1.15g, 2.4 mmol) under
the usual conditions gave a dark brown oil that was subjected
to column chromatography (2:1 CH Cl /hexanes). Concentra-
tion of the fractions (R 0.35) afforded 3k (400 mg, 86%) as an
unstable yellow oil: 1H NMR δ 6.85 (dd, J ) 1.9, 1.9 Hz, 2H),
.84-3.82 (m, 2H), 2.31 (dt, J ) 6.9, 1.5 Hz, 1H), 2.21 (dt, J )
6.9, 1.5 Hz, 1H), 2.07(m, 6H), 1.93-1.84 (m, 10H), 1.79-1.62
m, 14H); 13C NMR δ 193.6, 145.5, 141.9, 100.4, 86.5, 72.6,
56.6, 47.1. 38.2, 36.7, 28.1; IR νmax 2959, 2937, 2928, 2917,
δ 143.1, 143.1, 113.6, 97.9, 86.6, 0.1; IR νmax 3020, 2961, 2900,
-1
21 24 2
C H O
2
2
143, 2125, 1409, 1291, 1251, 1187, 1032, 959, 849 cm ; UV-
vis (hexanes) λmax (log ꢀ, cyclohexane) 328 (3.4) nm; MS 286
(70), 218 (60), 203 (100), 73 (31).
1
2
3f).
,3-Bis(p h en ylet h yn yl)b icyclo[2.2.1]h ep t a -2,5-d ien e
1
8b
(
The reaction of diiodonium 1a (796 mg, 1.00 mmol)
2
2
with alkynylstannane 2d (939 mg, 2.4 mmol) under the usual
conditions gave an orange oil that was subjected to column
chromatography (1:99 ethyl acetate/hexanes). Concentration
f
3
f
of the fractions (R 0.30) afforded 3f (270 mg, 92%) as a light
1
yellow oil: H NMR δ 7.52-7.49 (m, 4H), 7.39-7.31 (m, 6H),
(
6
)
1
.90 (dd, J ) 1.9, 1.9 Hz, 2H), 3.82-3.78 (m, 2H), 2.33 (dt, J
1
3
6.7, 1.5 Hz, 1H), 2.19 (dt, J ) 6.7, 1.5 Hz, 1H); C NMR δ
2
7
907, 2872, 2853, 2177, 2170, 1659, 1452, 1232, 1224, 1022,
36, 657 cm ; UV-vis λmax (log ꢀ, hexanes) 334 (3.7) nm; MS
42.2, 141.8, 131.6, 128.5, 128.5, 123.7, 103.4, 86.2, 71.6, 56.3;
-
1
IR νmax 3061, 2993, 2942, 2868, 2187, 1484, 1443, 1297, 754,
-
1
136 (100) 135 (52).
7
3
2
2
20, 689, 617 cm ; UV-vis (hexane) λmax (log ꢀ, cyclohexane)
50 (4.3) nm; MS 292 (62), 226 (100); HRMS calcd for C23
92.1252, found 292.1259; calcd for M - C
26.0783, found 226.0799.
H
16
Ack n ow led gm en t. Financial support by the NCI of
NIH (CA16903) is gratefully acknowledged.
5
H
6
(C18
H
10
)
2
,3-Bis(p h en yleth yn yl)-7-oxa bicyclo[2.2.1]h ep ta -2,5-d i-
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra of
en e (3g). The reaction of diiodonium 1b (399 mg, 0.50 mmol)
with alkynylstannane 2d (469 mg, 1.2 mmol) under the usual
conditions gave an orange oil that was subjected to radial
chromatography (1:40 ethyl acetate/hexanes). Concentration
of the fractions (R
yellow oil: H NMR δ 7.55-7.50 (m, 4H), 7.40-7.34 (m, 6H),
compounds 3a -k (11 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.
f
0.25) afforded 3g (80 mg, 54%) as a light
1
J O960750K