Silylene transfer to carbonyl compounds and subsequent Ireland-Claisen rearrangements to control formation of quaternary carbon stereocenters

Article abstract of DOI:10.1021/ja042893r

In this communication, we demonstrate that silylene transfer to carbonyl compounds provides a new method for regio- and stereoselective enolate formation. Silylene transfer to a range of α,β-unsaturated esters under silver-catalyzed conditions proved to be a general method for the formation of oxasilacyclopentenes containing a cyclic silyl ketene acetal functionality. These oxasilacyclopentenes are useful synthetic intermediates that can undergo facile and selective Ireland-Claisen rearrangements and aldol addition reactions to provide products with multiple contiguous stereocenters and quaternary carbon centers. Copyright

Full text of DOI:10.1021/ja042893r

Published on Web 01/27/2005
Silylene Transfer to Carbonyl Compounds and Subsequent Ireland-Claisen
Rearrangements to Control Formation of Quaternary Carbon Stereocenters
Stacie A. Calad and K. A. Woerpel*
Department of Chemistry, UniVersity of California, IrVine, California 92627-2025
Received November 24, 2004; E-mail: kwoerpel@uci.edu
Table 1. Silylene Transfer to R,â-Unsaturated Esters
Silylenes (R2Si) react with the carbon-oxygen double bond of
carbonyl compounds to afford a variety of products. For example,
silylene transfer to aldehydes and ketones produce cyclic siloxanes1-7
and silyl enol ethers8-10 via oxasilacyclopropane11 or silacarbonyl
ylide12 intermediates. Reactions of silylenes with R,â-unsaturated
ketones provide oxasilacyclopentenes containing a cyclic silyl enol
ether functionality.5,13,14 Although the reactions of silylenes with
carbonyl compounds were first reported nearly 30 years ago, these
reactions have not been applied to organic synthesis. In this
communication, we demonstrate that silylene transfer to R,â-
unsaturated carbonyl compounds provides a stereoselective method
for the synthesis of compounds possessing quaternary carbon
stereocenters.15,16
We became interested in silylene transfer to carbonyl compounds
during our studies on the metal-catalyzed silacyclopropanation of
alkenes.17,18 While alkenes substituted with a hindered pivaloate
ester underwent silylene transfer to the alkene, those bearing an
enolizable ester reacted preferentially at the carbonyl group. When
isobutyrate 1 was treated with cyclohexene silacyclopropane 2 and
a catalytic amount of AgOTf, silylene transfer to the carbonyl group
was observed, providing silanol 3 as the major product (eq 1).19
Oxasilacyclopropane 4 likely formed as an intermediate in the
reaction,20 and rearrangement of this intermediate led to formation
of the product. The enhanced reactivity of the carbonyl group over
the alkene is consistent with the electrophilic nature of the metal
silylenoid intermediate that is transferred.21,22
a As determined by 1H NMR spectroscopic analysis of the product relative
to an internal standard (PhSiMe3). b Oxasilacyclopentene 7a was isolated
in a drybox and obtained by recrystallization in 76% yield. c Isolated yields.
When the R,â-unsaturated ester ethyl tiglate (8) was exposed to
silylene transfer conditions followed by treatment with water, â-silyl
ester 9 was obtained with high diastereoselectivity (eq 3). Observa-
Silver-catalyzed silylene transfer to a range of R,â-unsaturated
carbonyl compounds demonstrated that both carbonyl and alkene
functional groups reacted to afford oxasilacyclopentene products
(eq 2, Table 1). These reactions likely occurred through nucleophilic
attack of the carbonyl group onto an electrophilic silver silylenoid
intermediate21 to form a silacarbonyl ylide 6 followed by an
electrocyclic ring closure (eq 2).9,23,24 With enoates 5a-d, highly
reactive oxasilacyclopentenes were obtained and characterized by
NMR spectroscopy because isolation of these silyl ketene acetals
proved difficult.25,26 Oxasilacyclopentenes 7e-f derived from
ketones 5e-f were found to be more stable than those derived from
esters,25 and these compounds were isolated by column chroma-
tography. Entry 6 is noteworthy, because silylene transfer to the
R,â-unsaturated ketone results in the synthetic equivalent of
regioselective enolization.27
tion of the reaction mixture by NMR spectroscopy revealed the
presence of an oxasilacyclopentene in 92% yield, which hydrolyzed
to form ester 9.9 The high diastereoselectivity obtained in this
hydrolysis suggested that oxasilacyclopentenes might serve as useful
intermediates for stereoselective synthetic transformations.
Since oxasilacyclopentenes obtained from R,â-unsaturated esters
contain the silyl enol ether functionality embedded within the ring,
we considered silylene transfer as a method for the stereoselective
9
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J. AM. CHEM. SOC. 2005, 127, 2046-2047
10.1021/ja042893r CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
formation of tetrasubstituted silyl ketene acetals.28 Silylene transfer
to the R,â-unsaturated ester moiety of allyl methacrylate (10)
occurred instead of transfer to the terminal alkene (eq 4). Intermedi-
Acknowledgment. This research was supported by the National
Institute of General Medical Sciences of the National Institutes of
Health (GM54909). S.A.C. thanks the National Institutes of Health
for a predoctoral fellowship. K.A.W. thanks Merck Research
Laboratories and Johnson & Johnson for awards to support research.
We thank Dr. Phil Dennison for assistance with NMR spectroscopy,
Dr. Joseph W. Ziller for X-ray crystallography, and Dr. John
Greaves and Dr. John Mudd for mass spectrometry.
Supporting Information Available: Experimental procedures;
spectroscopic, analytical, and X-ray data for the products (PDF, CIF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
ate oxasilacylopentene 11 underwent an Ireland-Claisen rearrange-
ment29,30 to provide silalactone 12 with the formation of an all-
carbon quaternary center.31 Adding substitution to the â-position
of the unsaturated ester afforded products 15a-b with high
diastereoselectivities and three contiguous stereocenters (eq 5).32
This stereochemistry may arise through a chairlike transition
structure (14) in which the allyl fragment approaches the face
opposite to the â-methyl group.
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