Cascade radical cyclizations via biradicals generated from (Z)-1,2,4-heptatrien-6-ynes

Article abstract of DOI:10.1021/ja9622620

On heating in refluxing benzene, acyclic enyne-allene 4 underwent intramolecular transformations in a sequence with an initial Myers cycloaromatization to form α,3-didehydrotoluene biradical 5 followed by a 5-exo cyclization of the benzenoid radical cente

Full text of DOI:10.1021/ja9622620

J. Am. Chem. Soc. 1996, 118, 10783-10791
10783
Cascade Radical Cyclizations via Biradicals Generated from
(Z)-1,2,4-Heptatrien-6-ynes
Kung K. Wang,*,† Zhongguo Wang,† Anna Tarli,† and Peter Gannett‡
Contribution from the Department of Chemistry and School of Pharmacy,
West Virginia UniVersity, Morgantown, West Virginia 26506
ReceiVed July 3, 1996X
Abstract: On heating in refluxing benzene, acyclic enyne-allene 4 underwent intramolecular transformations in a
sequence with an initial Myers cycloaromatization to form R,3-didehydrotoluene biradical 5 followed by a 5-exo
cyclization of the benzenoid radical center in 5 to produce 6. Biradical 6 then decayed through a 1,5-hydrogen shift
to furnish o-quinodimethane 7, which in turn was captured in an intramolecular Diels-Alder reaction to afford 8
having the tetracyclic steroidal skeleton in a single step from 4 in 50% isolated yield. Similarly, acyclic enyne-
allene 16 having one of the tethers shortened by one carbon atom furnished 18 having the fused 5,6,6,5-ring system.
Tetracycle 19 substituted with an angular methyl group was obtained from 17. In the cases of 24 and 34, a predominant
1,5-hydrogen shift of an allylic hydrogen to the benzenoid radical center of biradicals 26 and 35 followed by a
homolytic coupling produced spiro derivatives 31 and 40, respectively. On the other hand, a preferential 7-endo
ring closure of biradicals 41 and 49, derived from 25 and 48, gave predominantly the tricyclic derivatives 46 and 54,
respectively. Similarly, cascade radical cyclizations via biradicals generated from enyne-allenes 67-70 produced
the bicyclic spiro compounds 77-80 having a four-membered ring.
Introduction
We recently reported a new method for synthesis of enyne-
allene 4 having two additional carbon-carbon double bonds
attached to the enyne-allene system by the synthetic sequence
outlined in Scheme 1.7b Lithiation of 5-(trimethylsilyl)-1,5,6-
octatriene with tert-butyllithium followed by B-methoxy-9-
Free radical reactions have many unique features, and their
synthetic applications are rapidly expanding.1 It is intriguing
to imagine the various possibilities of having two radical centers
in the same molecule simultaneously to induce synergistic and
cooperative effects between them and thereby create new
chemical transformations. Of the few reported methods for
generating biradicals suitable for subsequent synthetic
elaborations,2-6 the Myers cycloaromatization reaction of (Z)-
1,2,4-heptatrien-6-ynes (enyne-allenes) to R,3-didehydro-
toluene biradicals is particularly attractive because the reaction
occurs under mild thermal conditions2 and various synthetic
routes to enyne-allenes with diverse chemical structures are
becoming available.2,7
4
borabicyclo[3.3.1]nonane (B-MeO-9-BBN) and /3 BF3‚OEt2
produced γ-(trimethylsilyl)allenylborane 1. Condensation of 1
generated in situ with the conjugated allenic aldehyde 2
proceeded smoothly and furnished, after treatment with 2-ami-
noethanol, the condensation adduct 3. The subsequent H2SO4-
induced Peterson elimination produced 4 having predominantly
the Z geometry (Z:E ) 96:4). On heating in refluxing benzene,
acyclic enyne-allene 4 underwent intramolecular transforma-
tions in a sequence with an initial Myers cycloaromatization to
form R,3-didehydrotoluene biradical 5 followed by a 5-exo
cyclization of the benzenoid radical center in 5 to produce 6.
† Department of Chemistry.
‡ School of Pharmacy.
X Abstract published in AdVance ACS Abstracts, October 15, 1996.
(1) (a) Curran, D. P. Synthesis 1988, 417-439, 489-513. (b) Jasperse,
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S0002-7863(96)02262-7 CCC: $12.00 © 1996 American Chemical Society

10784 J. Am. Chem. Soc., Vol. 118, No. 44, 1996
Wang et al.
Scheme 1
Scheme 2
9
double bonds. Treatment of 1-hexen-5-yne (9)8 with BBr3
followed by esterification with isopropyl alcohol10 furnished the
corresponding (Z)-alkenylboronic ester 10 in 58% isolated yield.
The presence of a terminal carbon-carbon double bond in 9
did not appear to interfere with bromoboration. Conversion of
10 to enynyl iodide 12 was achieved by using the Pd(PPh3)4-
catalyzed cross-coupling reaction with alkynylzinc chloride
11,9,11 derived from 1-lithio-1-propyne and anhydrous zinc
Biradical 6 then decayed through a 1,5-hydrogen shift to furnish
o-quinodimethane 7, which in turn was captured in an intra-
molecular Diels-Alder reaction to afford 8 having the tetra-
cyclic steroidal skeleton in a single step from 4 in 50% isolated
yield.7b We now have extended this synthetic pathway to other
carbocyclic structures by varying the length of the tethers
connecting the two additional carbon-carbon double bonds to
the enyne-allene system. The use of simple alkyl side chains
attached to the enyne-allene system for cascade radical
cyclizations was also investigated.
chloride, followed by treatment with NaOH and iodine.10,12
A
second Pd(PPh3)4-catalyzed cross-coupling reaction between 12
and allenylzinc chloride 13,13 derived from treating 1,2,8-
nonatriene with n-butyllithium followed by anhydrous zinc
chloride, proceeded smoothly to furnish enyne-allene 4 having
predominantly the Z geometry (Z:E ) 97:3). Similarly, enyne-
allene 16 having one of the tethers shortened by one carbon
atom and 17 having a methyl substituent at the internal position
of one of the additional double bonds as well as a shorter tether
were synthesized by cross coupling with allenylzinc chlorides
14 and 15, derived from 1,2,7-octatriene and 7-methyl-1,2,7-
octatriene, respectively.
Results and Discussion
In addition to the method described in Scheme 1 for synthesis
of acyclic enyne-allenes, we also reported an alternative
procedure involving bromoboration of a terminal alkyne with
BBr3 followed by two consecutive Pd(PPh3)4-catalyzed cross-
coupling reactions with organozinc chlorides derived from
terminal alkynes and allenes.7c We elected to use this highly
convergent synthetic method at the outset to prepare acyclic
enyne-allenes 4, 16, and 17 for the cascade radical cyclizations
(Scheme 2). Enyne-allene 4 was again synthesized by this
new procedure in order to determine whether this synthetic
method will tolerate the presence of additional carbon-carbon
The thermally-induced cascade cyclization of 4, synthesized
by the procedure outlined in Scheme 2, gave essentially identical
results as observed previously (Scheme 1).7b The carbon
tetracycle 8 having predominantly the trans ring junction (trans:
cis ) 92:8) was obtained in 51% isolated yield (0.233 g, 0.971
mmol) by dropwise addition of a solution of 4 (0.460 g, 1.92
mmol) in 250 mL of benzene into 600 mL of refluxing benzene
over a period of 10 h followed by an additional 4 h of reflux.
The assignment of the trans ring junction to the major isomers
was based on the chemical shift correlation of the 13C NMR
signals with those of other closely related structures.14 Because
the stereogenic center on the five-membered ring did not exert
a significant influence on the facial selectivity of the Diels-
(7) (a) Andemichael, Y. W.; Gu, Y. G.; Wang, K. K. J. Org. Chem.
1992, 57, 794-796. (b) Andemichael, Y. W.; Huang, Y.; Wang, K. K. J.
Org. Chem. 1993, 58, 1651-1652. (c) Wang, K. K.; Wang, Z. Tetrahedron
Lett. 1994, 35, 1829-1832. (d) Wang, Z.; Wang, K. K. J. Org. Chem. 1994,
59, 4738-4742. (e) Ezcurra, J. E.; Pham, C.; Moore, H. W. J. Org. Chem.
1992, 57, 4787-4789. (f) Grissom, J. W.; Huang, D. J. Org. Chem. 1994,
59, 5114-5116. (g) Grissom, J. W.; Slattery, B. J. Tetrahedron Lett. 1994,
35, 5137-5140. (h) Wu, M.-J.; Lin, C.-F.; Wu, J.-S.; Chen, H.-T.
Tetrahedron Lett. 1994, 35, 1879-1882. (i) Sakai, Y.; Bando, Y.; Shishido,
K.; Shibuya, M. Tetrahedron Lett. 1992, 33, 957-960. (j) Schmittel, M.;
Strittmatter, M.; Kiau, S. Tetrahedron Lett. 1995, 36, 4975-4978. (k) Naoe,
Y.; Kikuishi, J.; Ishigaki, K.; Iitsuka, H.; Nemoto, H.; Shibuya, M.
Tetrahedron Lett. 1995, 36, 9165-9168. (l) Gillmann, T.; Hulsen, T.; Massa,
W.; Wocadlo, S. Synlett 1995, 1257-1259. (m) Shibuya, M.; Wakayama,
M.; Naoe, Y.; Kawakami, T.; Ishigaki, K.; Nemoto, H.; Shimizu, H.; Nagao,
Y. Tetrahedron Lett. 1996, 37, 865-868. (n) Schmittel, M.; Strittmatter,
M.; Vollmann, K.; Kiau, S. Tetrahedron Lett. 1996, 37, 999-1002. (o)
Krause, N.; Hohmann, M. Synlett 1996, 89-91. (p) Dai, W.-M.; Fong, K.
C.; Danjo, H.; Nishimoto, S.-i. Angew. Chem., Int. Ed. Engl. 1996, 35,
779-781.
(8) Priebe, H.; Hopf, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 286.
(9) (a) Satoh, Y.; Serizawa, H.; Miyaura, N.; Hara, S.; Suzuki, A.
Tetrahedron Lett. 1988, 29, 1811-1814. (b) Yamashina, N.; Hyuga, S.;
Hara, S.; Suzuki, A. Tetrahedron Lett. 1989, 30, 6555-6558.
(10) Brown, H. C.; Somayaji, V. Synthesis 1984, 919-920.
(11) King, A. O.; Okukado, N.; Negishi, E.-i. J. Chem. Soc., Chem.
Commun. 1977, 683-684.
(12) Brown, H. C.; Hamaoka, T.; Ravindran, N. J. Am. Chem. Soc. 1973,
95, 5786-5788.
(13) Ruitenberg, K.; Kleijn, H.; Meijer, J.; Oostveen, E. A.; Vermeer,
P. J. Organomet. Chem. 1982, 224, 399-405.
(14) Nicolaou, K. C.; Barnette, W. E.; Ma, P. J. Org. Chem. 1980, 45,
1463-1470.

Cascade Radical Cyclization
J. Am. Chem. Soc., Vol. 118, No. 44, 1996 10785
Alder reaction, a 1:1 mixture of the two diastereomers of the
Scheme 3
trans isomers of 8 was produced.7b
Thermolysis of enyne-allene 16 with a shorter tether was
likewise conducted in refluxing benzene to furnish 18 having
the fused 5,6,6,5-ring system in 39% yield (eq 1). The
tetracyclic compound 18 was found to be a 3:3:2:2 mixture of
all four possible diastereomers presumably because of a lack
of facial selectivity as well as little preference for either the
exo or the endo attack during the intramolecular Diels-Alder
reaction to capture the corresponding o-quinodimethane at the
last step of the cascade sequence.14 Placing a methyl substituent
at the internal position of one of the additional carbon-carbon
double bonds in 17 was intended to produce an angular methyl
group in the final tetracyclic structure. Indeed, 19 having the
5,6,6,5-ring system with an angular methyl group was obtained
as a 1:1:7:9 mixture of four diastereomers in 41% yield (eq 2).
The improved stereoselectivity is presumably due to a preference
for either an exo or an endo attack during the intramolecular
Diels-Alder reaction, producing either the cis or the trans ring
junction (not determined) predominantly.
Scheme 4
The possibility of constructing the fused 6,6,6,6-ring system
by using enyne-allene 24 having one of the tethers elongated
by one carbon atom compared to 4 for the cascade radical
cyclization was also investigated. Attempts to synthesize 24
by the reaction sequence outlined in Scheme 2 were un-
successful. Bromoboration of 1-hepten-6-yne with BBr3 fol-
lowed by treatment with isopropyl alcohol produced the desired
alkenylboronic ester only in very low isolated yield. The
reaction produced mostly an intractable tar. Fortunately, it was
possible to synthesize acyclic enyne-allene 24 (Z:E ) 97:3)
by reverting back to the reaction sequence outlined in Scheme
1 with an initial condensation between the conjugated allenic
aldehyde 2 and γ-(trimethylsilyl)allenylborane 20 to afford 22
followed by an H2SO4-induced Peterson elimination (Scheme
3).
Thermolysis of 24 produced, in addition to a small amount
of the anticipated tetracyclic compound 30 (ca. 4% isolated
yield, 1:1 mixture of two diastereomers) having the fused
6,6,6,6-ring system, the bicyclic spiro derivative 31 as the major
product (30:31 ) 6:94) (Scheme 4). Apparently, instead of
trapping the benzenoid radical in 26 by one of the intramolecular
carbon-carbon double bonds in a 6-exo fashion to afford
biradical 27 leading to 30, the majority of the reaction proceeded
through a 1,5-hydrogen shift to furnish 28 containing an allylic
radical. The preference for the benzenoid radical center in 26
to undergo a 1,5-hydrogen shift instead of the desired 6-exo
radical cyclization had also been observed in other closely
related systems.15 The subsequent attack on the ipso carbon of
the benzene ring by the terminus of the allylic radical led to
homolytic coupling that produced 31.
It was difficult to separate 31 from 30 by column chroma-
1
tography and HPLC. However, the H and 13C NMR spectra
of the crude reaction mixture obtained by simple removal of
benzene appeared to indicate a clean transformation of 24 to
30 and 31 (ca. 80-90%) with minor contamination from other
unidentified products. The assignment of the bicyclic spiro
structure to 31 was further supported by additional one- and
two-dimensional NMR measurements (COSY, HETCOR, and
DEPT). The exocyclic double bond in 31 was assigned the E
geometry on the basis of the measurement of the nuclear
Overhauser effect. We were able to isolate 30 only by treating
the crude reaction mixture with an excess of BH3‚SMe2 followed
by an oxidative treatment with alkaline H2O2 to convert 31 to
(15) (a) Grissom, J. W.; Calkins, T. L. J. Org. Chem. 1993, 58, 5422-
5427. (b) Grissom, J. W.; Calkins, T. L.; Huang, D.; McMillen, H.
Tetrahedron 1994, 50, 4635-4650. (c) Curran, D. P.; Kim, D.; Liu, H. T.;
Shen, W. J. Am. Chem. Soc. 1988, 110, 5900-5902. (d) Abeywickrema,
A. N.; Beckwith, A. L. J. J. Chem. Soc., Chem. Commun. 1986, 464-465.

10786 J. Am. Chem. Soc., Vol. 118, No. 44, 1996
Wang et al.
Scheme 5
Scheme 6
1
was heated at reflux in benzene, the H NMR spectrum of the
crude reaction mixture indicated the presence of the anticipated
tetracyclic adduct 45, which was later isolated (26% yield) and
identified as a 1:1 mixture of two diastereomers having the trans
ring junction. However, 45 remained as the minor adduct, and
1
a more predominant set of H NMR signals attributable to the
presence of the tricyclic derivative 46 (45:46 ) 35:65) were
observed (Scheme 6). Undoubtedly, the tricyclic derivative 46
arises from a 7-endo ring closure of 41 to furnish 43,16 leading
to 46 by attack on the benzene ring by the homobenzylic radical
center in 43 to accomplish homolytic coupling.
Again, it was only possible to separate 45 from 46 by treating
the crude reaction mixture with an excess of BH3‚SMe2 followed
by an oxidative treatment with alkaline H2O2 to convert 46 to
a more polar adduct, allowing isolation of 45 by column
chromatography. As in the case of 8, the tetracycle 45 appeared
to have predominantly the trans ring junction and exist as a 1:1
mixture of two diastereomers.
a more polar adduct, allowing isolation of 30 by column
chromatography.
Since one of the carbon-carbon double bonds in 24 did not
participate in the cascade radical cyclization to furnish the
bicyclic derivative 31, we therefore synthesized acyclic enyne-
allene 34 having only one additional double bond attached to
the enyne-allene system through a three-carbon tether by using
the conjugated allenic aldehyde 32 for condensation with 20 as
described previously (Scheme 5).7a Thermolysis of 34 indeed
produced the expected bicyclic spiro derivative 40 having a
simplified structure, thus facilitating structural elucidation. A
1
minor set of the H NMR signals attributable to the presence
Acyclic enyne-allene 48 was also synthesized as a simplified
analogue of 25 (Scheme 7). On heating in refluxing benzene,
48 was converted to the bicyclic adduct 53 and the tricyclic
derivative 54 as expected (53:54 ) 35:65) (Scheme 7). The
1H NMR spectrum of the crude reaction products also indicated
a clean conversion of 48 to 53 and 54 (ca. 80-90%). It was
possible to partially separate 53 from 54 by HPLC, allowing a
complete elucidation of the highly unusual structure of 54 by a
wide range of NMR experiments, including COSY, HETCOR,
NOESY, and DEPT.
of the tetrahydronaphthalene derivative 39 (39:40 ) 6:94) was
also observed. Apparently, o-quinodimethane 38 derived from
the 6-exo radical cyclization decayed through a 1,5-hydrogen
shift to produce 39 as observed previously.7a Again, the 1H NMR
spectrum of the crude reaction mixture indicated a relatively
clean transformation of 34 to 39 (ca. 5%) and 40 (76%). The
yields of 39 and 40 were determined by adding a carefully
determined amount of 1,4-dimethoxybenzene as an internal
standard to the crude reaction mixture for the 1H NMR
integration.
An attempt was made to try to eliminate the possibility of
the 1,5-hydrogen shift from 26 to 28 so as to direct the cascade
radical cyclization toward the 6-exo pathway leading to the fused
6,6,6,6-ring system. Enyne-allene 25 having two methyl
groups in place of the two allylic hydrogens in 24 was thus
synthesized for this purpose as outlined in Scheme 3. After 25
While tricyles 46 and 54 contain a strained four-membered
ring and do not possess aromaticity as in 45 and 53, the
transformations from 25 to 46 and from 48 to 54 can still be
expected to be highly exothermic. In each case, the overall
(16) Beckwith, A. L. J.; Schiesser, C. H. Tetrahedron 1985, 41, 3925-
3941.

Cascade Radical Cyclization
J. Am. Chem. Soc., Vol. 118, No. 44, 1996 10787
Scheme 7
Scheme 8
treatment with 2-aminoethanol afforded 63-66 with high
diastereoselectivity (de g92%). The subsequent H2SO4-induced
Peterson elimination of 63-66 at -20 °C then produced enyne-
allenes 67-70 (Z:E g 96:4) along with ca. 2-6% of the
cycloaromatized adducts 71-74.
It was observed previously that the Myers cyclization of (Z)-
7-methyl-3,5,6-octatrien-1-yne having only a small hydrogen
atom at the acetylenic terminus occurred at 37 °C with a half-
life of ca. 70 min. Similarly, cyclizations of enyne-allenes 67-
70 also occurred readily at room temperature, and the reactions
were found to be complete within 18 h, significantly faster than
those of enyne-allenes 34 and 48 having a methyl substituent
at the acetylenic terminus. The faster rates of cyclizations of
67-70 are responsible for the formation of small amounts of
the cycloaromatized adducts 71-74 (2-6%) even though the
Peterson elimination of 63-66 was carried out at -20 °C to
try to prevent their formation.
transformation involves trading three π bonds for three σ bonds,
a driving force of ca. 60 kcal/mol. Nevertheless, the attack on
the ipso carbon of the benzene ring by the homobenzylic radical
in 43 and 51 is remarkable and must overcome the formation
of a strained four-membered ring along with the loss of
aromaticity. Evidently, the gain in forming a σ bond by the
intramolecular radical-radical combination is enough to over-
ride these unfavorable factors. However, this σ bond must be
significantly weakened with lower bond energy, making 46 and
54 reactive and prone to decomposition.
In comparison with 46 and 54, the transformations from 24
to 31 and from 34 to 40 involve converting only two π bonds
to two σ bonds. But unlike 46 and 54, the structures of 31 and
40 do not contain a strained four-membered ring. The pos-
sibility of attacking the ipso carbon of the benzene ring by the
terminus of the allylic radical in 28 and 37 alleviates the
constraint of forming a four-membered ring via the intramo-
lecular radical-radical combination. This option will not be
available if the 4-pentenyl substituent of the enyne-allene
system in 24 and 34 is replaced with a propyl group which then
could lead to the formation of a bicyclic spiro structure having
a four-membered ring. Enyne-allenes 67-70 (Scheme 8) were
synthesized to test the feasibility of producing such a bicyclic
spiro structure via cascade biradical cyclizations.
The cascade radical cyclization of 67 was conducted at high
dilution (ca. 3 × 10-4 M) in benzene, and the mixture was
stirred at room temperature for 18 h. Benzene was then
removed in Vacuo, and 1 mL of C6D6 was added along with a
carefully determined amount of 1,4-dimethoxybenzene as an
1
internal standard for the H NMR integration to determine the
yields of the reaction products. It was gratifying to observe
that the 1H NMR spectrum of the concentrated reaction mixture
indicated the presence of the bicyclic spiro compound 77 in
9% yield (Scheme 9). The amount of the cycloaromatized
adduct 71 (9%) did not appear to be significantly more than
what was originally present (6%) in the starting enyne-allene
67. It was possible to separate out a small amount of 77 by
1
HPLC for structural elucidation by the H NMR and MS.
Treatment of terminal allenes 55-58 with n-butyllithium
followed by B-MeO-9-BBN and 4/3 BF3‚OEt2 produced γ-(tri-
methylsilyl)allenylboranes 59-62. Condensation of 59-62
generated in situ with the allenic aldehyde 32 followed by
Apparently 77 arises from a reaction pathway involving an
initial formation of the R,3-didehydrotoluene biradical 75
followed by an intramolecular 1,5-hydrogen shift to form 76,

10788 J. Am. Chem. Soc., Vol. 118, No. 44, 1996
Wang et al.
Scheme 9
propensity for decomposition in large portions during removal
of benzene in Vacuo to produce more concentrated samples in
1
order to allow determination of the yields by the H NMR
integration using 1,4-dimethoxybenzene as the internal standard.
Scheme 10
Enyne-allene 70 having an additional carbon-carbon double
bond attached to the enyne-allene system with a six-carbon
tether was synthesized in order to study the possibility of
capturing the secondary alkyl radical center in 82 by the terminal
double bond intramolecularly in a typical 5-exo fashion to give
a new biradical 83 (Scheme 10). It was hoped that perhaps 83
could undergo an intramolecular radical-radical combination
by attacking the ipso carbon of the benzene ring to furnish 84.
Furthermore, since the rate constant for the 5-exo radical
cyclization of 85 (k5-exo ) 1.5 × 105 s-1 at 25 °C) having a
secondary alkyl radical center had been reported (eq 6),16
which then undergoes an intramolecular radical-radical com-
bination by attacking the ipso carbon of the benzene ring to
furnish 77. In comparison with the transformation from 37 to
40, the homolytic coupling of 76 to form 77 suffers from the
formation of a strained four-membered ring. However, the
primary alkyl radical in 76 is more reactive than the allylic
radical in 37.
determination of the relative yield between 80 and the adducts
derived from biradical 83 would allow an estimation of the rate
constant of the transformation from 82 to 80. While there was
no evidence that 84 was produced, the formation of 80 in 36%
yield indicates that the direct attack of the secondary alkyl
radical in 82 on the ipso carbon of the benzene ring to furnish
80 is very facile and at least competitive with the 5-exo radical
cyclization of 82 to form 83.
Interestingly when enyne-allene 67 was dissolved in C6D6
at a higher concentration (ca. 0.4 M) in order to allow the
1
progress of the reaction to be monitored by the H NMR, the
presence of the bicyclic spiro compound 77 was not detected
after 18 h at room temperature. Instead, the cycloaromatized
adduct 71 was produced in 34% yield. Presumably, at higher
concentration the intermolecular disproportionation of bi-
radicals 75 or 76 became more favorable in producing 71
predominantly. A similar concentration effect in directing the
course of the reaction of the biradical intermediates derived from
the Moore cyclization of enyne-ketenes was also observed
previously.4e
Similarly, keeping enyne-allenes 68, 69, and 70 in benzene
at high dilution furnished the bicyclic spiro adducts 78 (13%),
79 (20%), and 80 (36%), respectively (eqs 3-5), along with
ca. 1-3% of the cycloaromatized adducts 72-74 which were
originally present in the starting enyne-allenes. The strained
spiro compounds 77-80 appeared to be labile and showed
Conclusions
The cascade radical cyclizations via biradicals generated from
acyclic enyne-allenes provide new pathways to the fused
tetracyclic structures in a single step. The presence of two
radicals in the same molecule simultaneously also creates
opportunities to allow new interactions between these reactive
centers, making it possible to form highly unusual and reactive
chemical structures not easily accessible by other synthetic
methods.

Cascade Radical Cyclization
J. Am. Chem. Soc., Vol. 118, No. 44, 1996 10789
H, ddt, J ) 17.1, 10.2, and 6.6 Hz), 5.05 (1 H, dm, J ) 17 and 2 Hz),
4.98 (1 H, dm, J ) 10 and 2 Hz), 4.40 (2 H, septet, J ) 6.1 Hz), 2.56
(2 H, t, J ) 7.3 Hz), 2.32 (2 H, q, J ) 7 Hz), 1.17 (6 H, d, J ) 6.0
Hz); 13C NMR (CDCl3) δ 137.43, 136.57, 124 (br), 115.59, 66.50,
43.41, 32.20, 24.44; MS m/e 275 and 273 (M+ - 15), 209.
Experimental Section
General procedures for manipulation of organoboranes and other
organometallic reagents were described previously.17 All reactions were
conducted in oven-dried (120 °C) glassware under a nitrogen atmo-
sphere. Tetrahydrofuran (THF) and diethyl ether (Et2O) were distilled
from sodium benzophenone ketyl prior to use. The following reagents
were purchased from Aldrich Chemical Co., Inc., and were used without
further purification: BBr3, BH3‚SMe2, 9-borabicyclo[3.3.1]nonane (9-
BBN-H), Pd(PPh3)4, ZnCl2, LiBr, 2-aminoethanol, 1,7-octadiene,
3-methyl-1,2-butadiene, 5-bromo-1-pentene, 8-bromo-1-octene, methyl
propargyl ether, methyl 3,3-dimethyl-4-pentenoate, propargyl chloride,
3-butyn-2-ol, chlorotrimethylsilane, methylmagnesium chloride (3.0 M
in THF), allylmagnesium bromide (1.0 M in Et2O), tert-butyllithium
(1.7 M in pentane), and n-butyllithium (2.5 M in hexanes). Hexa-
methylphosphoric triamide (HMPA) was also purchased from Aldrich
and was distilled from CaH2 prior to use. 2,3,9-Decatrienal (2),7b
1-hexen-5-yne (9),8 1,2,8-nonatriene,18 4-methyl-2,3-pentadienal (32),19
5-bromo-2-methyl-1-pentene,20 B-methoxy-9-borabicyclo[3.3.1]nonane
(B-MeO-9-BBN),21 3-(trimethylsilyl)-1,2-hexadiene (55),22 3-(trimeth-
ylsilyl)-1,2-heptadiene (56),22 and 6-methyl-3-(trimethylsilyl)-1,2-hep-
tadiene (57)22 were prepared according to the reported procedures.
6-(Trimethylsilyl)-1,6,7-nonatriene was obtained in 78% isolated yield
by sequential treatment of a dispersion of CuBr and LiBr in THF with
4-pentenylmagnesium bromide in THF and the methanesulfonate of
4-(trimethylsilyl)-3-butyn-2-ol as described previously.22 Similarly, 3,3-
dimethyl-6-(trimethylsilyl)-1,6,7-nonatriene (70% yield) and 3-(tri-
methylsilyl)-1,2,10-undecatriene (58, 84% yield) were prepared from
3,3-dimethyl-4-pentenylmagnesium bromide and 7-octenylmagnesium
bromide, respectively. 5-Bromo-3,3-dimethyl-1-pentene23 was prepared
by reducing methyl 3,3-dimethyl-4-pentenoate with LiAlH4 (86%)
followed by treating the methanesulfonate of the resulting alcohol with
LiBr in refluxing acetone for 6 h (64%). Silica gel (70-230 mesh)
for column chromatography was also obtained from Aldrich. Cuprous
bromide was purchased from Fluka, and 1-propyne was obtained from
Farchan. 1H (270 MHz) and 13C (67.9 MHz) NMR spectra were
recorded in CDCl3 or C6D6 using Me4Si, CHCl3 (1H δ 7.26), CDCl3
(13C δ 77.02), C6D5H (1H δ 7.15), or C6D6 (13C δ 128.00) as internal
standard. Nuclear Overhauser effect, DEPT, and two-dimensional
NMR (DQCOSY, HETCOR, NOESY) spectra were obtained at 300
MHz at 25 °C. Standard pulse sequences were used. T1 analysis was
performed to ensure a sufficient delay period was used between NOE
irradiation pulses. Mass spectra were obtained at 70 eV.
(Z)-1-Iodo-2-(1-propynyl)-1,5-hexadiene (12). To a 100 mL flask
were added 5.78 g of 10 (20.0 mmol), 1.15 g of Pd(PPh3)4 (1.0 mmol),
and 20 mL of dry THF. The mixture was degassed by three cycles of
freeze-thaw and kept under a nitrogen atmosphere at room temperature
for 1 h. In a second flask, 1-propynylzinc chloride was prepared by
treating a degassed solution of 1-propyne (25 mmol) in 40 mL of THF
with 10 mL of a 2.5 M solution of n-butyllithium (25 mmol) in hexanes
for 10 min followed by the addition of a degassed solution of 3.4 g of
anhydrous zinc chloride (25.0 mmol) in 5 mL of THF. The solution
of 1-propynylzinc chloride was then transferred via cannula into the
first flask at room temperature. After 5 min, the reaction mixture was
heated at reflux for 3 h before being cooled to 0 °C and was treated
sequentially with 32 mL of a 6 N NaOH and 12.7 g of iodine (50
mmol) in 20 mL of Et2O. After 1 h of stirring at room temperature,
an excess of saturated Na2S2O3 solution was introduced to reduce I2.
An additional 30 mL of Et2O was added, and the organic layer was
separated. The aqueous layer was extracted with Et2O (3 × 20 mL).
The combined organic layers were dried over MgSO4 and concentrated.
The residue was purified by column chromatography (silica gel/hexanes)
to furnish 2.46 g (10.0 mmol, 50%) of 12 as a light yellow liquid: IR
1
(neat) 2227, 1640, 994, 915 cm-1; H NMR (CDCl3) δ 6.31 (1 H, s),
5.77 (1 H, ddt, J ) 17.1, 10.2, and 6.3 Hz), 5.03 (1 H, dm, J ) 17 and
2 Hz), 4.98 (1 H, dm, J ) 10 and 1 Hz), 2.30 (4 H, br), 2.03 (3 H, s);
13C NMR (CDCl3) δ 137.05, 136.71, 115.37, 93.13, 82.30, 80.63, 38.67,
32.34, 4.65; MS m/e 246 (M+), 205, 119.
(Z)-5-(1-Propynyl)-1,5,7,8,14-pentadecapentaene (4).7b To a de-
gassed solution of 0.49 g of 1,2,8-nonatriene18 (4.0 mmol) in 10 mL
of THF at -70 °C was added 1.6 mL of a 2.5 M solution of
n-butyllithium (4.0 mmol) in hexanes. After 2 h at -70 °C, a degassed
solution of 0.545 g of anhydrous zinc chloride (4.0 mmol) in 10 mL
of THF was introduced via cannula followed by a degassed mixture of
0.984 g of 12 (4.0 mmol) and 0.231 g of Pd(PPh3)4 (0.20 mmol) in 10
mL of THF. The reaction mixture was then charged with 5 mL of
HMPA and was allowed to warm to room temperature. After 2 h, 30
mL of a saturated NH4Cl solution and 30 mL of pentane were added,
and the organic layer was separated. The aqueous layer was extracted
with pentane (3 × 20 mL), and the combined organic layers were dried
over MgSO4 and concentrated. The residue was purified by column
chromatography (silica gel/hexanes) to furnish 0.617 g (2.57 mmol,
64%) of 4 (Z:E ) 97:3) as a light yellow liquid: IR (neat) 2232, 1940,
1641, 993, 911 cm-1; 1H NMR (C6D6) δ 6.76 (1 H, ddt, J ) 10.8, 6.4,
and 3 Hz), 6.16 (1 H, d, J ) 10.8 Hz), 5.75 (1 H, ddt, J ) 17, 10, and
6 Hz), 5.73 (1 H, ddt, J ) 17, 10, and 6 Hz), 5.26 (1 H, q, J ) 6.8
Hz), 5.05-4.90 (4 H, m), 2.30 (2 H, q), 2.21 (2 H, t), 1.90 (4 H, m),
1.61 (3 H, s), 1.30 (4 H, m); 13C NMR (C6D6) δ 208.63, 138.95, 138.03,
130.94, 123.32, 115.08, 114.59, 93.50, 92.87, 92.31, 78.46, 37.43, 33.85,
33.16, 28.92, 28.81, 28.59, 4.15; MS m/e 240 (M+), 225, 197.
(5r)-(()-15-Methylgona-8,11,13-triene (8).7b A solution of 0.460
g (1.92 mmol) of 4 in 250 mL of degassed dry benzene was introduced
dropwise to 600 mL of refluxing benzene (degassed) under a nitrogen
atmosphere over a period of 10 h followed by an additional 4 h of
reflux. Benzene was then removed by simple distillation. In order to
facilitate separation and purification, the residue was treated with an
excess of a 0.5 M solution of 9-BBN-H in THF at room temperature
for 2 h followed by oxidation with an excess of alkaline H2O2 (30%).
Pentane (25 mL) was added, and the organic layer was separated,
washed with water, and concentrated. Purification by column chro-
matography (silica gel/hexanes) furnished 0.233 g (0.971 mmol, 51%)
of 8 (trans:cis ) 92:8) as a colorless liquid: IR (neat) 1475, 1446, 811
cm-1; 1H NMR (CDCl3) δ 7.225 (d, J ) 7.9 Hz) and 7.213 (d, J ) 7.7
Hz) (1 H, the aromatic hydrogens of the two diastereomers), 7.11 (1
H, d, J ) 7.7 Hz), 3.32 (1 H, septet, J ) 7.3 Hz), 3.15-3.0 (1 H, m),
2.9-2.7 (3 H, m), 2.52 (1 H, d, J ) 12.6 Hz), 2.4-2.2 (2 H, m), 2.0-
1.8 (5 H, m), 1.6-1.2 (6 H, m), 1.247 and 1.228 (3 H, d, J ) 7 Hz);
13C NMR (CDCl3) δ 147.28, 147.12, 140.33, 140.23, 138.61, 138.42,
132.92, 132.66, 124.00, 123.69, 121.66, 44.15, 43.69, 40.62, 40.20,
38.25, 37.81, 34.47, 34.40, 34.17, 33.97, 31.58, 31.29, 30.70, 30.59,
(Z)-(2-Bromo-1,5-hexadienyl)diisopropoxyborane (10). To a so-
lution of 6.58 g of 1-hexen-5-yne (9)8 (82.3 mmol) in 30 mL of dry
pentane under a nitrogen atmosphere at -78 °C was added with a
syringe 7.6 mL of BBr3 (20.1 g, 80 mmol). After 1 h at -78 °C, the
mixture was allowed to warm to room temperature and stirred overnight.
The solution was then cooled to -20 °C and transferred via cannula
into a second flask containing a mixture of 50 mL of 2-propanol and
50 mL of pentane at -20 °C. After 30 min, the top layer was separated,
and the bottom layer was extracted with cold pentane (3 × 20 mL).
The top layer and the pentane extracts were combined and concentrated.
The residue was then distilled at reduced pressure (64-66 °C/0.06 Torr)
to furnish 13.3 g (46.1 mmol, 58%) of 10 as a colorless liquid: IR
(neat) 1641, 989, 915 cm-1; 1H NMR (CDCl3) δ 5.97 (1 H, s), 5.76 (1
(17) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M. Organic
Syntheses Via Boranes; Wiley-Interscience: New York, 1975.
(18) Skattebol, L. J. Org. Chem. 1966, 31, 2789-2794.
(19) Clinet, J. C.; Linstrumelle, G. NouV. J. Chem. 1977, 1, 373-374.
(20) (a) Pirrung, M. C. J. Am. Chem. Soc. 1981, 103, 82-87. (b) van
der Gen, A.; Wiedhaup, K.; Swoboda, J. J.; Dunathan, H. C.; Johnson, W.
S. J. Am. Chem. Soc. 1973, 95, 2656-2663.
(21) Kramer, G. W.; Brown, H. C. J. Organomet. Chem. 1974, 73, 1-15.
(22) (a) Westmijze, H.; Vermeer, P. Synthesis 1979, 390-392. (b)
Danheiser, R. L.; Carini, D. J.; Fink, D. M.; Basak, A. Tetrahedron 1983,
39, 935-947. (c) Danheiser, R. L.; Tsai, Y.-M.; Fin, D. M. Org. Synth.
1987, 66, 1-7. (d) Wang, K. K.; Liu, C.; Gu, Y. G.; Burnett, F. N.;
Sattsangi, P. D. J. Org. Chem. 1991, 56, 1914-1922. (e) Wang, K. K.;
Gu, Y. G.; Liu, C. J. Am. Chem. Soc. 1990, 112, 4424-4431.
(23) Beckwith, A. L. J.; Easton, C. J.; Lawrence, T.; Serelis, A. K. Aust.
J. Chem. 1983, 36, 545-556.
(24) Moreau, J.-L.; Gaudemar, M. J. Organomet. Chem. 1976, 108, 159-
164.

10790 J. Am. Chem. Soc., Vol. 118, No. 44, 1996
Wang et al.
30.52, 30.19, 27.20, 27.10, 26.96, 26.32, 26.25, 26.23, 18.90, 18.86;
MS m/e 240 (M+), 225, 212, 197; HRMS calcd for C18H24 240.1878,
found 240.1883. Due to the presence of a stereogenic center on the
five-membered ring, the isolated material contains two diastereomers
in essentially 1:1 ratio. A minor set of doublets (8%) at ca. δ 7.09
and 7.01 (J ) 7.9 Hz) in the H NMR spectrum is attributed to the
signals of the aromatic hydrogens of the isomers having the cis ring
junction.
spiro structure to 31 was further supported by additional NMR
measurements, including COSY, HETCOR, and DEPT. Because 31
is prone to decomposition, its elemental composition was not further
analyzed.
The fused tetracycle 30 was separated from 31 by treating the residue
in THF with an excess of BH3‚SMe2 followed by an oxidative treatment
with alkaline H2O2 (30%) to convert 31 to a more polar adduct, allowing
isolation of 0.0164 g (0.065 mmol, ca. 4%) of 30 (1:1 mixture of two
diastereomers) by column chromatography (silica gel/hexanes) as a
liquid: 1H NMR (C6D6) δ 7.19 (1 H, d, J ) 8 Hz), 6.96 (1 H, d, J )
7.9 Hz), 2.95 (1 H, m), 2.8-2.6 (4 H, m), 2.37 (1 H, m), 2.21 (1 H, t),
1.9-1.5 (8 H, m), 1.4-1.1 (6 H, m), 1.14 and 1.10 (3 H, d, J ) 7.0
Hz); MS m/e 254 (M+), 239, 211; HRMS calcd for C19H26 254.2035,
found 254.2055.
1
(6R,7R)-6-(1-Propynyl)-6-(trimethylsilyl)-1,8,9,15-hexadecatetraen-
7-ol (22). To a solution of 1.164 g of 6-(trimethylsilyl)-1,6,7-nonatriene
(6.00 mmol) in 20 mL of THF at -78 °C was introduced with a syringe
3.5 mL of a 1.7 M solution of tert-butyllithium (6.0 mmol) in pentane.
After 0.5 h of stirring at -78 °C and then 1 h at -40 °C, 1.0 mL of
B-MeO-9-BBN (0.91 g, 6.0 mmol) was added, and the reaction mixture
was allowed to warm to 0 °C. After 40 min, 1.0 mL of BF3‚OEt2
(1.13 g, 8.0 mmol) was introduced. The reaction mixture was kept at
0 °C for 15 min and then was allowed to warm to room temperature.
After 15 min, the solution was cooled to 0 °C, and 0.90 g (6.0 mmol)
of 2 was introduced. The reaction mixture was allowed to warm to
room temperature. After 2 h, THF and pentane were removed at
reduced pressure under a stream of dry N2, and the pressure was then
restored with N2. Pentane (30 mL) was added followed by 1.0 mL of
2-aminoethanol, and a white precipitate formed almost immediately.
After 15 min, the precipitate was removed by filtration (inert nitrogen
atmosphere no longer needed), and the filtrate was washed with water,
dried over MgSO4, and concentrated. The residue was purified by
column chromatography (silica gel/hexanes and then 2.5% of ethyl
acetate in hexanes) to furnish 1.399 g (4.07 mmol, 68%) of 22 as a
yellow liquid: IR (neat) 3560, 2167, 1962, 1641, 1247, 992, 911, 842
cm-1; 1H NMR (C6D6) δ 5.9-5.65 (3 H, m), 5.19 (1 H, m), 5.08-4.94
(4 H, m), 4.49 (1 H, m), 2.05 (2 H, m), 1.95-1.85 (4 H, m), 1.85-1.7
(4 H, m), 1.54 and 1.53 (3 H, s), 1.30 (4 H, m), 0.315 and 0.312 (9 H,
s); 13C NMR (C6D6) δ 202.14, 201.80, 138.98, 138.86, 114.69, 95.57,
95.35, 95.09, 94.98, 81.62, 81.54, 80.00, 73.61, 73.15, 35.12, 35.07,
34.38, 33.98, 33.87, 33.84, 30.69, 30.48, 29.02, 28.90, 28.68, 26.59,
3.59, -1.24, -1.27; MS m/e 344 (M+), 326, 73. Because of an
essentially random selection of the allenic chiral axis during condensa-
tion which was of no chemical consequence in producing 24, the
isolated material was a 1:1 mixture of two diastereomers.
(Z)-6-(1-Propynyl)-1,6,8,9,15-hexadecapentaene (24). To 10 mL
of a 1:1 mixture of pentane and Et2O containing 70 mg of concentrated
H2SO4 at 0 °C was added 1.39 g (4.04 mmol) of 22 in 10 mL of a 1:1
mixture of pentane and Et2O. After 1 h of vigorous stirring at 0 °C,
20 mL of water and 20 mL of pentane were added. The organic layer
was then separated, dried over MgSO4, and concentrated. The residue
was purified by column chromatography (silica gel/pentane) to furnish
0.839 g (3.30 mmol, 81%) of 24 (Z:E ) 97:3) as a colorless liquid:
IR (neat) 2224, 1940, 1640, 992, 911 cm-1; 1H NMR (C6D6) δ 6.75 (1
H, ddt, J ) 10.6, 6.4, and 3.1 Hz), 6.17 (1 H, d, J ) 10.4 Hz), 5.71 (2
H, ddt, J ) 17.0, 10.3, and 6.6 Hz), 5.27 (1 H, q, J ) 6.8 Hz), 5.03-
4.90 (4 H, m), 2.13 (2 H, t, J ) 7.5 Hz), 2.0-1.85 (6 H, m), 1.64 (2
H, quintet, J ) 7.5 Hz), 1.62 (3 H, s), 1.30 (4 H, m); 13C NMR (C6D6)
δ 208.59, 138.95, 138.70, 130.81, 123.84, 114.84, 114.60, 93.55, 92.65,
92.31, 78.59, 37.25, 33.86, 33.34, 28.95, 28.83, 28.61, 28.12, 4.19;
MS m/e 254 (M+), 239, 211.
(Z)-10-Methyl-6-(1-propynyl)-1,6,8,9-undecatetraene (34). The
same procedure was repeated as described for 24 except that 33 (0.50
g, 1.72 mmol) was used to furnish 0.290 g (1.45 mmol, 84%) of 34
(Z:E ) 96:4) as a colorless liquid: IR (neat) 2224, 1946, 1640, 992,
911 cm-1; 1H NMR (C6D6) δ 6.69 (1 H, d of septet, J ) 10.8 and 2.8
Hz), 6.17 (1 H, dm, J ) 10.8 and 0.5 Hz), 5.71 (2 H, ddt, J ) 17.1,
10.2, and 6.7 Hz), 4.98 (1 H, dm, J ) 17 and 1.5 Hz), 4.93 (1 H, dm,
J ) 11 and 1 Hz), 2.15 (2 H, td, J ) 7.7 and 1 Hz), 1.96 (2 H, q, J )
7.1 Hz), 1.66 (2 H, quintet, J ) 7.3 Hz), 1.63 (3 H, s), 1.59 (6 H, d,
J ) 2.9 Hz); 13C NMR (C6D6) δ 206.36, 138.74, 131.63, 123.32, 114.77,
96.20, 92.35, 91.75, 78.72, 37.27, 33.37, 28.16, 20.43, 4.16; MS m/e
200 (M+), 185, 146; HRMS calcd for C15H20 200.1565, found 200.1569.
8-(1-Methylethenyl)-1,2,3,4-tetrahydro-1,2,2-trimethylnaphtha-
lene (53) and 1,2,3,3a,4,6-Hexahydro-3,3,5-trimethyl-6-(1-methyl-
ethylidene)cyclopenta[1,4]cyclobuta[1,2]benzene (54). The same
procedure was repeated as described for 8 except that 48 (0.256 g,
1.12 mmol) was used. Benzene was removed by simple distillation,
and the 1H NMR spectrum of the residue indicated a clean transforma-
tion of 48 to 53 and 54 (ca. 80-90%) (53:54 ) 35:65). Compounds
53 and 54 were partially separated by preparative HPLC to allow
structural elucidations. 53: 1H NMR (C6D6) δ 7.03 (1 H, d, J ) 7.8
Hz), 6.91 (1 H, d, J ) 7.8 Hz), 5.16 (1 H, m, J ) 0.9 Hz), 4.93 (1 H,
m, J ) 0.9 Hz), 2.72 (2 H, dd, J ) 10 and 7 Hz), 2.60 (1 H, q, J ) 6.6
Hz), 2.25 (3 H, s), 1.96 (3 H, m), 1.77 (1 H, ddd, J ) 13, 11, and 8
Hz), 1.17 (1 H, dd, J ) 13 and 6 Hz), 1.01 (3 H, d, J ) 6.6 Hz), 0.96
(3 H, s), 0.84 (3 H, s); 13C NMR (C6D6) δ 147.72, 142.62, 141.60,
133.10, 132.13, 126.89, 125.63, 114.52, 41.16, 32.30, 29.58, 29.01,
26.94 (2 carbons), 25.04, 18.08, 15.42; MS m/e 228 (M+), 213, 199.
54: 1H NMR (C6D6) δ 6.62 (1 H, d, J ) 9.2 Hz), 5.84 (1 H, d, J ) 9.2
Hz), 2.51 (1 H, dd, J ) 15 and 8 Hz), 2.41 (1 H, dd, J ) 15 and 6 Hz),
2.10 (1 H, t, J ) 6.5 Hz), 1.91 (3 H, s), 1.82 (3 H, s), 1.81 (2 H, m),
1.72 (3 H, s), 1.38 (2 H, m), 0.90 (3 H, s), 0.87 (3 H, s); 13C NMR
(C6D6) δ 142.20, 132.98, 131.09, 127.41, 127.35, 123.93, 60.65, 55.86,
42.05, 38.58, 36.54, 30.40, 27.26, 23.63, 23.26, 21.29, 17.80; MS m/e
228 (M+), 213, 199. The structures of 53 and 54 were further supported
by additional one- and two-dimensional NMR measurements (COSY,
HETCOR, NOESY, and DEPT). Because 54 is prone to decomposi-
tion, its elemental composition was not further analyzed.
(3R,4R)-3-Butyl-7-methyl-3-(trimethylsilyl)-5,6-octadien-1-yn-
4-ol (64). To 0.99 g (5.90 mmol) of 3-(trimethylsilyl)-1,2-heptadiene
(56) in 20 mL of THF at -78 °C was added with a syringe 2.1 mL of
a 2.5 M solution of n-butyllithium (5.3 mmol) in hexanes. After 0.5
h at -78 °C, 0.92 mL of B-MeO-9-BBN (0.83 g, 5.3 mmol) was added,
and the reaction mixture was allowed to warm to 0 °C. After 40 min,
0.87 mL of BF3‚OEt2 (0.98 g, 6.9 mmol) was introduced, and the
reaction mixture was stirred at 0 °C for 15 min and then at room
temperature for 15 min. The solution was cooled to 0 °C, and 0.52 g
(5.3 mmol) of the conjugated allenic aldehyde 32 in 5 mL of THF was
added. After 0.5 h of stirring at room temperature, the mixture was
concentrated with a water aspirator under a slow stream of nitrogen to
half its original volume, and the pressure was restored with nitrogen.
Hexanes (29 mL) was added followed by 0.70 mL of 2-aminoethanol,
and a white precipitate appeared almost immediately. After 15 min,
the precipitate was removed by filtration (inert nitrogen atmosphere
no longer needed), and the filtrate was washed with water, dried over
Na2SO4, and concentrated. The residue was purified by column
chromatography (silica gel/hexanes and then 2% diethyl ether in
hexanes) to furnish 0.889 g (3.36 mmol, 63%) of 64 (RR/SS:RS/SR )
(6ar,10aâ)-1,2,3,4,5,6,6a,7,8,9,10,10a-Dodecahydro-4-methyl-
chrysene (30) and (E)-3-(6-Heptenylidene)-2-methylspiro[5.5]undeca-
1,4,8-triene (31). The same procedure was repeated as described for
8 except that 24 (0.360 g, 1.42 mmol) was used. Benzene was removed
by simple distillation, and the 1H NMR spectrum of the residue indicated
a clean transformation of 24 to 30 and 31 (ca. 80-90%) (30:31 )
6:94). The presence of 31 in the residue can be clearly identified. The
spiro derivative 31 exhibited the following spectral data: IR (neat) 1640,
992, 909 cm-1; 1H NMR (C6D6) δ 6.54 (1 H, d, J ) 10.1 Hz), 5.85 (1
H, dt, J ) 10.1 and 1.8 Hz), 5.72 (1 H, ddt, J ) 17, 10, and 7 Hz),
5.67 (1 H, m), 5.61 (1 H, s), 5.59 (1 H, m), 5.40 (1 H, t, J ) 7.5 Hz),
4.98 (1 H, dm, J ) 17 and 2 Hz), 4.94 (1 H, dm, J ) 10 and 1 Hz),
2.15 (2 H, q, J ) 7 Hz), 2.00 (2 H, m), 1.96 (4 H, m), 1.82 (3 H, d,
J ) 1.1 Hz), 1.51 (2 H, t, J ) 6.3 Hz), 1.31 (4 H, m); 13C NMR (C6D6)
δ 138.97, 135.70, 133.03, 132.39, 130.58, 126.42, 125.00, 124.23,
121.76, 114.65, 37.81, 37.17, 34.49, 34.07, 29.84, 29.02, 27.52, 22.44,
19.95; MS m/e 254 (M+), 200, 118. The assignment of the bicyclic

Cascade Radical Cyclization
J. Am. Chem. Soc., Vol. 118, No. 44, 1996 10791
96:4) as a yellow liquid: IR (neat) 3553, 3310, 2093, 1968, 1247, 841
cm-1; 1H NMR (C6D6) δ 5.59 (1 H, d of septet, J ) 5 and 3 Hz), 4.50
(1 H, t, J ) 5 Hz), 1.96 (1 H, s), 1.81-1.64 (5 H, m), 1.54 (3 H, d, J
) 2.8 Hz), 1.52 (3 H, d, J ) 3.0 Hz), 1.31 (2 H, sextet, J ) 7.1 Hz),
0.91 (3 H, t, J ) 7.3 Hz), 0.33 (9 H, s); 13C NMR (C6D6) δ 199.65,
99.95, 92.85, 87.30, 73.33, 72.70, 34.04, 30.19, 29.28, 24.03, 20.58,
20.39, 14.24, -1.45; MS m/e 264 (M+), 249, 221, 73. Anal. Calcd
for C16H28OSi: C, 72.66; H, 10.67. Found: C, 72.64; H, 10.78.
(9R,10R)-9-Ethynyl-13-methyl-9-(trimethylsilyl)-1,11,12-tetra-
decatrien-10-ol (66). The same procedure was repeated as described
for 64 except that 3-(trimethylsilyl)-1,2,10-undecatriene (58, 1.03 g,
4.60 mmol) was used to prepare 62 for condensation with the conjugated
allenic aldehyde 32 (0.40 g, 4.2 mmol) to afford 0.743 g (2.33 mmol,
56%) of 66 (RR/SS:RS/SR > 97:3) as a yellow liquid: IR (neat) 3553,
and 1 Hz), 2.94 (1 H, s), 2.10 (2 H, t, J ) 7.1 Hz), 1.92 (2 H, q, J )
7 Hz), 1.56 (6 H, d, J ) 2.8 Hz), 1.52 (2 H, m), 1.3-1.1 (6 H, m). The
isolated material contained ca. 2% of the cycloaromatized adduct 74.
Because cycloaromatization of 70 occurs relatively rapidly at room
temperature, the isolated material was used immediately without
additional measurements of the spectral data and the elemental
composition.
7-(1-Methylethylidene)-1-(4-pentenyl)spiro[3.5]nona-5,8-diene (80).
A solution of 0.062 g (0.27 mmol) of enyne-allene 70 in 880 mL of
benzene was stirred at room temperature under a nitrogen atmosphere
for 18 h. The reaction mixture was then divided into two portions of
equal volume. The first portion was placed in a 1000-mL flask and
then was concentrated in Vacuo with a water aspirator to ca. 1 mL,
and the concentrated solution was transferred into a 25-mL flask. The
1000-mL flask was rinsed with 10 mL of hexanes, and the hexanes
solution was transferred to the 25-mL flask. The combined solutions
were concentrated in Vacuo with a water aspirator to ca. 1 mL and
then briefly at 0.5 Torr. The residue was dissolved in 1 mL of C6D6
along with 0.031 g (0.22 mmol) of 1,4-dimethoxybenzene as an internal
standard for the 1H NMR integration. The yield of 80 (36%) was
determined by comparing the integrations of the signal of the aromatic
hydrogens of 1,4-dimethoxybenzene at δ 6.74 with that of the olefinic
hydrogen of 80 at δ 6.64. In addition, the reaction mixture was found
to contain 3% of the cycloaromatized adduct 74. The second portion
was likewise concentrated, and a small amount of 80 was isolated by
HPLC (silica/hexanes): 1H NMR (C6D6) δ 6.64 (1 H, dd, J ) 10.3
and 2.2 Hz), 6.47 (1 H, dd, J ) 10.0 and 2.1 Hz), 5.99 (1 H, dd, J )
10.3 and 1.8 Hz), 5.72 (1 H, ddt, J ) 17.0, 10.3, and 6.9 Hz), 5.67 (1
H, dd, J ) 10 and 2 Hz), 4.98 (1 H, dm, J ) 17 and 2 Hz), 4.94 (1 H,
dm, J ) 10 and 1 Hz), 2.12 (1 H, quintet, J ) 8 Hz), 1.95-1.75 (5 H,
m), 1.66 (3 H, s), 1.64 (3 H, s), 1.61 (1 H, m), 1.5-1.2 (4 H, m); 13C
NMR (C6D6) δ 139.16, 135.29, 129.93, 126.23, 123.99, 122.58, 114.45,
48.13, 45.70, 34.17, 33.96, 31.85, 26.62, 23.33, 20.03, 19.97; MS m/e
228 (M+), 213, 185; HRMS calcd for C17H24 228.1878, found 228.1888.
1
3310, 2092, 1968, 1640, 1247, 996, 910, 842 cm-1; H NMR (C6D6)
δ 5.76 (1 H, ddt, J ) 17.0, 10.1, and 6.7 Hz), 5.60 (1 H, d of septet,
J ) 4.9 and 3.0 Hz), 5.02 (1 H, dm, J ) 17 and 1 Hz), 4.97 (1 H, dm,
J ) 10 and 1 Hz), 4.50 (1 H, t, J ) 4.9 Hz), 1.96 (1 H, s), 1.96 (2 H,
q, J ) 6.7 Hz), 1.82-1.75 (3 H, m), 1.73 (OH, d, J ) 4.9 Hz), 1.58
(1 H, m), 1.56 (3 H, d, J ) 3.0 Hz), 1.53 (3 H, d, J ) 3.0 Hz), 1.35-
1.22 (6 H, br), 0.34 (9 H, s); 13C NMR (C6D6) δ 199.64, 139.14, 114.47,
99.93, 92.85, 87.28, 73.30, 72.70, 34.12, 34.09, 30.84, 30.46, 29.38,
29.33, 27.08, 20.62, 20.40, -1.45; MS m/e 318 (M+), 275, 73; HRMS
calcd for C20H34OSi - CH3 303.2144, found 303.2132 (M+ - CH3).
(Z)-9-Ethynyl-13-methyl-1,9,11,12-tetradecatetraene (70). To a
250-mL round-bottomed flask containing 3.0 mL of a 1:1 mixture of
pentane and Et2O and 0.07 g of concentrated H2SO4 at -20 °C was
added via cannula 0.10 g (0.31 mmol) of 66 in 3.0 mL of a 1:1 mixture
of pentane and Et2O at -20 °C. The reaction mixture was stirred
vigorously at -20 °C to spread the concentrated H2SO4 over a large
surface area on the bottom of the flask, and the progress of the reaction
was monitored with TLC (Et2O:hexanes ) 1:5). After 30 min, the
Peterson elimination was complete, and 10 mL of pentane at 0 °C was
added. The reaction mixture was poured into a separatory funnel
containing 10 mL of cold water. The aqueous layer was separated,
and the organic layer was washed with cold water (3 × 10 mL). The
combined aqueous layers were extracted with cold pentane (3 × 10
mL). The combined organic layers were then quickly filtered through
a short column packed with silica gel and MgSO4 by applying pressure
at the top of the column with nitrogen, and the column was finally
eluded with 10 mL of cold pentane. The filtrate was collected at -20
°C to keep cycloaromatization of 70 to a minimum. Pentane was then
evaporated in Vacuo to furnish 0.062 g (0.27 mmol, 87%) of 70 (Z:E
) 97:3) as a colorless liquid: IR (neat) 3304, 2082, 1939, 1639, 989,
910 cm-1; 1H NMR (C6D6) δ 6.63 (1 H, d of septet, J ) 10.9 and 2.9
Hz), 6.24 (1 H, dq, J ) 10.9 and 1 Hz), 5.75 (1 H, ddt, J ) 17.0, 10.3,
and 6.6 Hz), 5.01 (1 H, dm, J ) 17 and 2 Hz), 4.97 (1 H, dm, J ) 11
Acknowledgment. The financial support of the National
Science Foundation (CHE-9307994) to K.K.W. is gratefully
acknowledged.
Supporting Information Available: Synthetic procedures
for 16-19, 23, 25, 33, 39, 40, 45-48, 63, 65, 67-69, 71, and
77-79 and 1H and/or 13C NMR spectra of 4, 8, 10, 12, 16-19,
22-25, 31, 33, 34, 40, 45, 47, 48, 53, 54, 63-71, and 77-80
(74 pages). See any current masthead page for ordering and
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