C O MMU N I C A T I O N S
cyclization of the isomeric Z,Z-bis-allylic silane 6.12 We have
previously reported an example of MeAlCl2-induced tricyclization
that proceeds exclusively via a chair-boat A/B closure route.13 Our
results show that the design of substrates that selectively favor one
cyclization pathway over the other may be possible in chemical
systems as well as for enzymes.7,14
Scheme 2
As mentioned above, the stereocontrolled transformation of vinyl
TBS ethers into the corresponding vinyl triflates (including E or Z
geometry) proved useful in the above-described syntheses of 1 and
7 (Schemes 1 and 2). The process is quite general, as illustrated by
the six examples in Table 1.15
The remarkably short and efficient (four steps, 31% overall yield)
synthesis of 1 which has been presented in this paper demonstrates
the power of modern synthetic chemistry and illustrates well the
value of the underlying methodology.
Acknowledgment. We are grateful to Pfizer Inc. for generous
research support and also to the Swiss National Science Foundation
for a Postdoctoral Fellowship to J.V.S.
Supporting Information Available: Experimental procedures and
physical data for the products shown in Schemes 1 and 2 (PDF). This
References
(1) Barton, D. H. R.; Overton, K. H. J. Chem. Soc. 1955, 2639.
(2) Stork, G.; Meisels, A.; Davies, J. E. J. Am. Chem. Soc. 1963, 85, 3419.
(3) (a) Corey E. J.; Sauers, R. R. J. Am. Chem. Soc. 1957, 79, 3925. (b)
Corey, E. J.; Sauers, R. R. J. Am. Chem. Soc. 1959, 81, 1739. (c) For
later synthetic studies in this area, see: Tsuda, Y.; Kashiwaba, N.; Kajitani,
M.; Yasui, J. Chem. Pharm. Bull. 1981, 29, 3424 and references cited
therein.
Table 1. Preparation of Vinyl Triflates from Vinyl TBS Ethers
(4) Corey, E. J.; Noe, M. C.; Lin, S. Tetrahedron Lett. 1995, 36, 8741.
(5) Corey, E. J.; Zhang, J. Org. Lett. 2001, 3, 3211.
(6) (a) Corey, E. J.; Lin, S. J. Am. Chem. Soc. 1996, 118, 8765. (b) Corey,
E. J.; Lin, S.; Luo, G. Tetrahedron Lett. 1997, 38, 5771. (c) Huang, A.
X.; Xiong, Z.; Corey, E. J. J. Am. Chem. Soc. 1999, 121, 9999. (d) Corey,
E. J.; Luo, G.; Lin, S. J. Am. Chem. Soc. 1997, 119, 9927.
(7) See: Wendt, K. U.; Schulz, G. E.; Corey, E. J.; Liu, D. R. Angew. Chem.,
Int. Ed. 2000, 39, 2813.
(8) Gramstad, T.; Haszeldine, R. N. J. Chem. Soc. 1956, 173.
(9) Prolonged reaction time for the conversion of 4 to 5 should be avoided
since 5 can undergo CsF-promoted elimination of CF3SO3 and the trans
olefinic â-hydrogen to form an acetylenic linkage. The formation of 5
from 4 requires all the reactants, since it does not occur with CF3SO2F
alone or with CF3SO2F-CsF mixtures in DME. It is apparent that the
triflimide reagent plays a role in solubilizing CsF and promoting fluoride-
induced silyl ether cleavage.
(10) The in situ generation of CF3SO2F results in a modest pressure (ca. 0.5
atm) buildup. Although CF3SO2F is commercially available, the in situ
generation is both convenient and more economical. If CF3SO2F is allowed
to escape from the reaction mixture, little or no vinyl triflate can be
isolated.
(11) Pauli, G. F. Planta Medica 2000, 66, 299.
(12) (a) It is also noteworthy that the cyclization of 11 produces only two
tetracyclic products, 7 (major) and 1 (minor), and no detectable (by 500
MHz 1H NMR and TLC analysis) amount of the C2-symmetric diastere-
omer of 1 that would result from a double chair-chair A/B folding
cyclization pathway. (b) For a general review of cationic cyclization
involving allylic silanes, see: Fleming, I.; Barbero, A.; Walter, D. Chem.
ReV. 1997, 97, 2063.
the three-component coupling product 9 in 77% yield, the new
olefinic linkages being formed only in the E geometry.6b,e The bis-
vinyl-TBS-silyl ether 9 was converted, as above for 4 f 5, into
the corresponding bis-E-vinyl triflate 10, and thence, as for 5 f 6
above, into the bis-allylic TMS compound 11. Both 10 and 11 were
isomerically pure (i.e., free of isomers 5 and 6, respectively), as
shown by 500 MHz 1H NMR analysis. Tetracyclization of 11 using
MeAlCl2 in CH2Cl2 at -94 °C for 15 min (same conditions as for
6 f 1 + 7 in Scheme 1) gave, after fluoride treatment, the tetracycle
7 (44%) and, surprisingly, (+)-R-onocerin (19%). The transforma-
tions shown in Scheme 2 not only establish the structure and
stereochemistry of 7 (when taken together with the spectral data)
but also show conclusively that the MeAlCl2-induced cation-olefin
cyclizations of 6 and 11 (especially 11) proceed to a significant
extent through chair-boat A/B transition states (steroid A/B
folding7). The chair-boat A/B pathway is clearly more favorable
in the cyclization of the E,E-bis-allylic silane 11 than in the
(13) Corey, E. J.; Wood, H. B., Jr. J. Am. Chem. Soc. 1996, 118, 11982.
(14) See also: Yee, N. K. N.; Coates, R. M. J. Org. Chem. 1992, 57, 4598.
(15) The following general procedure was used for the transformations of vinyl
TBS ethers to vinyl triflates (eight examples) reported herein. Into a flame-
dried, round-bottom flask flushed with dry N2 and fitted with a magnetic
stirrer were quickly placed dry PhN(SO2CF3)2 (2-3 equiv), dry CsF (3-4
equiv, 1 equiv more than PhN(SO2CF3)2, dried in vacuo for 12 h at 300
°C), and a solution of the vinyl TBS ether dissolved in DME (freshly
distilled from sodium benzophenone ketyl). The flask was connected to
a three-way stopcock by a ground glass joint sealed with Teflon tape to
prevent the escape of gaseous CF3SO2F. Reactions were conducted with
vigorous stirring under N2 at 23 °C, followed by cooling of the contents,
withdrawing a small sample by syringe, and analyzing by TLC or 1H
NMR. Upon completion of the reaction (or near completion in the case
of triflates having trans-â-H to the triflate leaving group), the reaction
mixture was vented and partitioned between pentane and pH 7 phosphate
buffer. The aqueous phase was extracted with pentane or ether (for more
water-soluble substrates), and the combined extracts were dried, concen-
trated in vacuo, and purified by rapid chromatography on silica gel.
JA027373F
9
J. AM. CHEM. SOC. VOL. 124, NO. 38, 2002 11291