Insertions of silylenes into vinyl epoxides: Diastereoselective synthesis of functionalized, optically active trans-dioxasilacyclooctenes

Article abstract of DOI:10.1021/ja906204a

(Chemical Equation Presented) This communication describes a direct route to functionalized nonracemic trans-dioxasilacyclooctenes that involves stereoselective silylene insertions into vinyl epoxides to provide vinyl silaoxetane intermediates. These stra

Full text of DOI:10.1021/ja906204a

Published on Web 09/21/2009
Insertions of Silylenes into Vinyl Epoxides: Diastereoselective Synthesis of
Functionalized, Optically Active trans-Dioxasilacyclooctenes
Michel Pre´vost and K. A. Woerpel*
Department of Chemistry, UniVersity of California, IrVine, California 92697-2025
Received July 23, 2009; E-mail: kwoerpel@uci.edu
trans-Cyclooctenes1 are unique members of the medium-ring
trans-cycloalkene family. These strained cyclic compounds display
stable planar chirality2 at ambient temperature and adopt a crown
conformation in which the olefin is severely distorted and has
partially pyramidalized sp2 carbons.3 As a consequence, reactions
where olefinic carbon centers undergo sp2 to sp3 rehybridization
are greatly accelerated4 and occur selectively on the face of the
olefin outside the ring.5 Although many synthetic routes to trans-
cyclooctenes have been reported,1,5b,6 preparation of functionalized7
nonracemic trans-cyclooctenes remains a challenge. Consequently,
general applications of these compounds in organic synthesis have
not emerged.8
silylene insertion into 7 and 10, respectively) did not show any
epimerization at the allylic position (Scheme 1).
Scheme 1. Insertions of Silylenes into cis- and trans-Vinyl
Epoxides
In this communication, we describe a reaction sequence that
capitalizes on metal-catalyzed silylene insertion conditions devel-
oped in our laboratory9 and the characteristics of trans-cyclooctenes
to generate synthetically valuable molecules. This process involves
stereospecific silylene insertions into the carbon-oxygen bonds of
allylic epoxides to form reactive vinyl silaoxetane intermediates
that can undergo nucleophilic additions to a variety of aldehydes,
yielding strained trans-dioxasilacyclooctenes.
The insertions of silylenes into epoxides were first studied with
vinyl epoxide 1. Treatment of this epoxide with silacyclopropane
2 and a catalytic amount of AgOTs at 25 °C cleanly provided a
new product (eq 1).10 1H NMR and 29Si NMR spectroscopy
indicated that this product was the silaoxetane 3, an allylic silane
with a silicon atom embedded in a strained ring.11
trans-Dioxasilacyclooctene 12 was obtained in lower yield
because of the concurrent formation of oxasilacyclohexene 14 along
with silaoxetane 11 during the silylene insertion step (Scheme 1
and eq 2).14 Oxasilacyclohexene 14 was probably generated through
a formal [2,3]-rearrangement of s-cis oxonium ylide 139 (eq 2).
The preference for 3,4-cis-vinyl epoxides to adopt s-trans confor-
mations15 could explain why silaoxetane 8 was formed selectively
from epoxide 7 (Scheme 1).
Spiroepoxides also undergo silylene insertion and subsequent
carbon-carbon bond formation. Silylene transfer to spiroepoxide
15 followed by addition of benzaldehyde and isobutyraldehyde
(eq 3) afforded as single diastereoisomers the corresponding
products 17 and 18 having trans double bonds in bridged eight-
membered rings (anti-Bredt olefins16).10 X-ray crystallographic
analysis of alkene 18 showed substantial twisting and pyramidal-
ization of the alkene, as detailed in the Supporting Information.
The high reactivity of strained allylic silanes suggested applica-
tions of these silaoxetanes for carbon-carbon bond-forming reac-
tions. Strained allylic silanes display enhanced nucleophilicity in
additions to unactivated aldehydes, serving as both the Lewis acid
and the nucleophilic allyl moiety.12,13 The reactivity of silaoxetane
3 was probed by addition of different aldehydes to the reaction
mixture after insertion of the silylene (eq 1). Products 4-6 with
trans double bonds in eight-membered rings were observed as single
diastereoisomers and atropisomers (eq 1). The relative stereochem-
istry of the products was unambiguously determined using NMR
spectroscopy.
Insertions of silylenes into vinyl epoxides and subsequent
allylation are highly stereoselective. trans-Dioxasilacyclooctenes
9 and 12 were formed as single diastereoisomers from 2,3-trans-
and 2,3-cis-vinyl epoxides 7 and 10, respectively (Scheme 1).
Spectroscopic data of vinylsilaoxetanes 8 and 11 (obtained after
The diastereoselectivity and scope of the silylene insertion-allyla-
tion sequence was established using enantiomerically enriched vinyl
epoxide (+)-19 (Scheme 2). After silylene insertion, addition of
9
14182 J. AM. CHEM. SOC. 2009, 131, 14182–14183
10.1021/ja906204a CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
glyoxylate 20 or chiral, nonracemic aldehyde (-)-21 to the reaction
mixture gave trans-dioxasilacyclooctene (-)-22 or (-)-23, respec-
tively, as single diastereoisomers.
In summary, the combination of insertion of silylenes into vinyl
epoxides and subsequent allylations of aldehydes represent a powerful
strategy for generating functionalized trans-dioxasilacyclooctenes.
Diastereoselective additions to these alkenes allow efficient transfer
of planar chirality to chirality at stereogenic carbon atoms.
Scheme 2. Synthesis of Nonracemic trans-Dioxasilacyclooctenes
Acknowledgment. This research was supported by the National
Institute of General Medical Sciences of the National Institutes of
Health (GM-54909). K.A.W. thanks Amgen and Lilly for awards to
support research. We thank Dr. P. Dennison (UCI) for the assistance
with NMR spectroscopy, Dr. J. W. Ziller (UCI) for X-ray crystal-
lography, and Dr. J. Greaves and Ms. S. Sorooshian (UCI) for mass
spectrometry. A Fonds Que´be´cois de la Recherche sur la Nature et
les Technologies Fellowship to M.P. is also gratefully acknowledged.
Supporting Information Available: Experimental procedures,
spectroscopic and analytical data for the product, and X-ray data (CIF)
for 18 and 25. This material is available free of charge via the Internet
at http://pubs.acs.org.
The diastereoselectivity of the addition of vinyl silaoxetanes to
aldehydes can be explained by considering chairlike six-membered
closed transition states A and B.17 In these transition states, the
silicon atoms bind to the aldehyde to form hypervalent complexes
with trigonal bipyramidal geometry (Scheme 3).12,18 Transition state
A, leading to trans-cycloalkene products, should be favored on the
basis of the preferential pseudoequatorial position19 of the -CH2-
group of the silaoxetane ring and basal position of the tert-butyl
groups in the trigonal bipyramidal complex. In contrast, formation
of the cis-cycloalkene through transition state B requires one tert-
butyl group to occupy an apical position, causing a severe steric
interaction between the two large tert-butyl groups.
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