Benzhydryldimethylsilyl allylic silanes: Syntheses and applications to [3 + 2] annulation reactions

Article abstract of DOI:10.1021/ol005676d

(Matrix Presented) A new silyl group, the benzhydryldimethylsilyl group, has been developed that is easily synthesized and that undergoes facile oxidation. The [3 + 2] annulation reactions of allylic silanes with this silyl group provide a variety of high

Full text of DOI:10.1021/ol005676d

ORGANIC
LETTERS
2000
Vol. 2, No. 10
1379-1381
Benzhydryldimethylsilyl Allylic Silanes:
Syntheses and Applications to [3 + 2]
Annulation Reactions
Zhi-Hui Peng and K. A. Woerpel*
Department of Chemistry, UniVersity of California, IrVine, California 92697-2025
kwoerpel@uci.edu
Received February 15, 2000
ABSTRACT
A new silyl group, the benzhydryldimethylsilyl group, has been developed that is easily synthesized and that undergoes facile oxidation. The
[3 + 2] annulation reactions of allylic silanes with this silyl group provide a variety of highly substituted five-membered carbocycles and
heterocycles with high stereoselectivities. The silyl groups of these cyclic compounds have been oxidized to hydroxyl groups to demonstrate
the general synthetic utility of the method.
The [3 + 2] annulation reactions of allylic silanes1 have
received much attention because they provide highly ste-
reoselective methods for the synthesis of functionalized five-
membered-ring carbocycles and heterocycles.2-8 Sterically
demanding silyl groups have been previously employed to
retard elimination processes9 and thus to favor the silyl
migration leading to the [3 + 2] annulation products. The
use of these hindered silanes has created other difficulties,
such as attenuated reactivity of the allylic silane and difficult
removal of the silyl moiety from the annulation product.10
Meyers et al. have introduced the trityldimethylsilyl moiety
as a solution to these problems, because the allylic silane
bearing this group is highly reactive, and the trityl unit may
be removed as trityl anion by fluoride ion, making this silane
readily oxidizable.5b,c
Although we had hoped to make use of the trityldimeth-
ylsilyl group in our own investigations of allylic silane
annulation chemistry,7a this moiety was not ideal for the
applications we envisioned. We required a short synthesis
of the silyl group, preferably as the silyl halide, but the
synthesis of trityldimethylsilyl bromide required three steps.11
In addition, the exceedingly large silyl moiety was anticipated
to be incompatible with our method for making highly
substituted allylic silanes by allylic substitution reactions.12
In this Letter, we describe the annulation reactions of allylic
silanes bearing the benzhydryldimethylsilyl group for the
synthesis of cyclopentanes,2,5 tetrahydrofurans,4,6 and pyr-
(1) Masse, C. E.; Panek, J. S. Chem. ReV. 1995, 95, 1293-1316.
(2) (a) Kno¨lker, H.-J.; Jones, P. G.; Pannek, J.-B. Synlett 1990, 429-
430. (b) Kno¨lker, H.-J.; Foitzik, N.; Goesmann, H.; Graf, R. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 1081-1083. (c) Kno¨lker, H.-J.; Wanzl, G. Synlett
1995, 378-382. (d) Kno¨lker, H.-J.; Jones, P. G.; Wanzl, G. Synlett 1998,
613. (e) Kno¨lker, H.-J. J. Prakt. Chem. 1997, 339, 304-314.
(3) (a) Danheiser, R. L.; Dixon, B. R.; Gleason, R. W. J. Org. Chem.
1992, 57, 6094-6097. (b) Danheiser, R. L.; Takahashi, T.; Bertok, B.;
Dixon, B. R. Tetrahedron Lett. 1993, 34, 3845-3848.
(4) (a) Akiyama, T.; Ishikawa, K.; Ozaki, S. Chem. Lett. 1994, 627-
630. (b) Akiyama, T.; Yasusa, T.; Ishikwa, K.; Ozaki, S. Tetrahedron Lett.
1994, 35, 8401.
(5) (a) Brengel, G. P.; Rithner, C.; Meyers, A. I. J. Org. Chem. 1994,
59, 5144-5146. (b) Brengel, G. P.; Meyers, A. I. J. Org. Chem. 1996, 61,
3230-3231. (c) Groaning, M. D.; Brengel, G. P.; Meyers, A. I. J. Org.
Chem. 1998, 63, 5517-5522.
(6) (a) Panek, J. S.; Yang, M. J. Am. Chem. Soc. 1991, 113, 9868-
9870. (b) Panek, J. S.; Beresis, R. J. Org. Chem. 1993, 58, 809-811. (c)
Panek, J. S.; Jain, N. F. J. Org. Chem. 1993, 58, 2345-2348. (d) Panek, J.
S.; Jain, N. F. J. Org. Chem. 1994, 59, 2674-2675.
(7) (a) Roberson, C. W.; Woerpel, K. A. J. Org. Chem. 1999, 64, 1434-
1435. (b) Isaka, M.; Williard, P. G.; Nakamura, E. Bull. Chem. Soc. Jpn.
1999, 72, 2115-2116.
(8) Other annulation pathways are also possible. For [2 + 2] annulations,
see: (a) Akiyama, T.; Kirino, M. Chem. Lett. 1995, 723-724. (b) Kno¨lker,
H.-J.; Baum, G.; Graf, R. Angew. Chem., Int. Ed. Engl. 1994, 33, 1612-
1615. For a formal [4 + 2] annulation, see: Angle, S. R.; El-Said, N. A.
J. Am. Chem. Soc. 1999, 121, 10211-10212.
(9) (a) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 17, 1295-1298.
(b) Sakurai, H. J. Am. Chem. Soc. 1977, 99, 1673-1674. (c) Hosomi, A.
Acc. Chem. Res. 1988, 21, 200-206.
(10) For reviews on the oxidation of silyl groups, see: (a) Tamao, K.
AdVances in Silicon Chemistry; JAI: Greenwich, CT, 1996; Vol. 3, pp 1-62.
(b) Fleming, I. Chemtracts-Org. Chem. 1996, 9, 1-64.
(11) Ager, D. J.; Fleming, I. J. Chem. Res., Miniprint 1977, 136-152.
10.1021/ol005676d CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/22/2000

rolidinones.7 This silyl group has several attributes that render
it well suited for annulation processes: (1) it can be easily
introduced to allylic silanes, including highly substituted
allylic silanes; (2) it is bulky enough to suppress Sakurai-
type products9 and to obtain [3 + 2] annulation products
with a variety of electrophiles; (3) it is tolerant to a variety
of synthetic procedures; and (4) it can be easily oxidized to
a hydroxyl group under mild conditions.
Scheme 2
The utility of the benzhydryldimethylsilyl moiety was
demonstrated by the reactions of the simplest allylic deriva-
tive allylbenzhydryldimethylsilane 1 with R,â-unsaturated
ketones. Allylbenzhydryldimethylsilane 1 could be prepared
by deprotonation of diphenylmethane followed by quenching
with commercially available allyldimethylchlorosilane (82%
yield, Scheme 1). The TiCl4-promoted [3 + 2] annulation
Scheme 1
the benzhydryldimethylsilyl group was sufficiently bulky to
undergo the 1,2-silyl migration over nucleophilic attack. The
benzhydryldimethylsilyl group of tetrahydrofuran 6 was
oxidized to afford alcohol 8 in good yield (Scheme 2). To
demonstrate that the benzhydryldimethylsilyl group could
withstand strongly reducing conditions, the ester moiety of
6 was reduced to provide alcohol 9 in high yield. Oxidation
of 9 provided diol 10 cleanly.
Having demonstrated the utility of the simple benzhy-
dryldimethylsilyl allylic silane in the [3 + 2] annulations,
we were interested in the use of substituted allylic silanes to
prepare more functionalized annulation products. The R-sub-
stituted (E)-benzhydryldimethylcrotylsilanes were prepared
using the procedure developed in our laboratory (Scheme
3).12 The requisite chlorosilane 11 was prepared directly from
of allylic silane 1 with enone 2 in the presence of 2,6-di-
tert-butylpyridine (DTBP) provided entirely the annulation
product 3 in 92% yield (Scheme 1).2,5b,c,13 Meyers’ procedure
for the oxidation of the trityldimethylsilyl group5b,c oxidized
the corresponding benzhydryldimethylsilyl group smoothly.14
Treatment of silane 3 with n-Bu4NF displaced the benzhydryl
group,15 and the resulting reaction mixture was exposed to
the Tamao conditions to yield alcohol 4 in high yield.
Scheme 3
Allylbenzhydryldimethylsilane 1 can be used for the
synthesis of five-membered heterocycles as well as carbo-
cycles. The [3 + 2] annulation of 1 and R-keto ester 54a
gave tetrahydrofuran 6 in 81% yield (Scheme 2).13 Only 5%
of the Sakurai product 7 was obtained, again indicating that
(12) (a) Smitrovich, J. H.; Woerpel, K. A. J. Am. Chem. Soc. 1998, 120,
12998-12999. (b) Smitrovich, J. H.; Woerpel, K. A. J. Org. Chem. 2000,
65, 1601-1614.
(13) For the annulation products 3, 6, and 20, only one diastereomer
was detected by 1H NMR spectroscopy, and the stereochemistry was
assigned by comparison to the analogous reported compounds (see refs 2,
4, 5, and 7). Furthermore, spectral data (1H and 13C NMR) obtained for 4
were identical to those reported by Kno¨lker and Meyers (refs 2c and 5c).
(14) The benzhydryl group was expected to be as good a leaving group
as the trityl group because they have comparable basicities: Bordwell, F.
G. Acc. Chem. Res. 1988, 21, 456-463.
(15) A recent work has shown that the benzylsilyl group can also be
oxidized to a hydroxy group with the same procedure: Miura, K.; Hondo,
T.; Nakagawa, T.; Takahashi, T.; Hosomi, A. Org. Lett. 2000, 2, 385-
388.
diphenylmethane and dichlorodimethylsilane in 70% yield.
Silylation of the THP ether of 3-butyn-2-ol (12) with
chlorosilane 11, followed by hydroboration and protonolysis
of the alkyne and removal of the THP group, afforded the
allylic alcohol with high (Z)-selectivity. This alcohol was
then treated with phenyl isocyanate to afford carbamate 14.
The copper-mediated SN2′ reactions of 14 provided (E)-
crotylsilanes 15 and 16 with high selectivities.12
1380
Org. Lett., Vol. 2, No. 10, 2000

Highly substituted benzhydryldimethylsilyl allylic silanes
15 and 16 undergo annulation reactions with high efficiency.
In the presence of BF3‚OEt2, allylic silane 15 reacted with
hydrocinnamaldehyde to give tetrahydrofuran 17 in high
yield as a single diastereomer by H NMR spectroscopic
analysis (Scheme 4). The two silyl groups of 17 could then
Benzhydryldimethylsilyl allylic silanes can also be utilized
for the preparation of nitrogen-containing heterocycles.
Previous work from our laboratory has shown that the [3 +
2] annulation of N-chlorosulfonyl isocyanate (CSI) with
allylic silanes provides a stereoselective synthesis of trisub-
stituted 2-pyrrolidinones.7a Benzhydrylsilane 16 underwent
annulation with CSI to furnish lactam 20 in 88% yield as a
single stereoisomer after in situ reduction with 25% Na2-
SO3 (Scheme 5).13 Oxidation of the benzhydryldimethylsilyl
1
Scheme 4
Scheme 5
group of 20 provided 4-hydroxy-2-pyrrolidinone 21 in 81%
yield without epimerization.
In conclusion, the benzhydryldimethylsilyl group has been
developed as a useful new silyl moiety for [3 + 2] annulation
reactions of allylic silanes. We have utilized this group to
prepare a variety of oxygenated five-membered ring systems
in high yields and with high stereoselectivities. The utility
of benzhydryldimethyl allylic silanes in annulation processes
has been demonstrated by our recent formal synthesis of (()-
peduncularine with a [3 + 2] annulation as a key step.21
be oxidized sequentially (Scheme 4). The benzhydryldi-
methylsilyl was first oxidized using the two-step, one-pot
procedure (n-Bu4NF/H2O2) to afford alcohol 18. Oxidation
of the terminal dimethylphenylsilyl group under acidic
conditions10 was not attempted because of concern about
â-elimination.16 Oxidation under basic conditions (t-BuOK/
DMSO)17 yielded none of the desired diol 19.18 Successful
oxidation was achieved by one-pot bromodesilylation/oxida-
tion (AcOOH/KBr),19 affording 19 in 75% yield. The
stereochemistry of diol 19 was proven by X-ray diffraction
analysis of its bis(3,5-dinitrobenzoate) derivative.20
Acknowledgment. This research was supported by a
CAREER Award from the National Science Foundation
(CHE-9701622). K.A.W. thanks the American Cancer So-
ciety, AstraZeneca, Glaxo-Wellcome, the Camille and Henry
Dreyfus Foundation, Merck, and the Research Corporation
for awards to support research. We thank Dr. John Greaves
and Dr. John Mudd for mass spectrometric data and Dr.
Joseph Ziller for X-ray crystallographic analyses.
(16) For example, see: Boons, G. J. P. H.; van der Marel, G. A.; van
Boom, J. H. Tetrahedron Lett. 1989, 30, 229-232.
(17) Murakami, M.; Suginome, M.; Fujimoto, K.; Nakamura, H.;
Anderson, P. G.; Ito, Y. J. Am. Chem. Soc. 1993, 115, 6487-6498.
(18) The â-elimination product 22 was obtained in 81% yield.
Supporting Information Available: Full experimental
and analytical data for all new compounds; X-ray data for a
1
derivative of 19; H NMR spectra of 3, 6, 15, 16, 17, and
20; and GC traces of 15 and 16. This material is available
(19) (a) Fleming, I.; Henning, R.; Parker, D. C.; Plaut, H. E.; Sanderson,
P. E. J. J. Chem. Soc., Perkin Trans. 1 1995, 317-337. (b) Fleming, I.;
Sanderson, P. E. J. Tetrahedron Lett. 1987, 28, 4229-4232.
(20) The stereochemistry is consistent with the anti-SE′ pathway through
an antiperiplanar transition state. See refs 1 and 6a,b.
free of charge via the Internet at http://pubs.acs.org.
OL005676D
(21) Roberson, C. W.; Woerpel, K. A. Org. Lett. 2000, 2, 621-623.
Org. Lett., Vol. 2, No. 10, 2000
1381