Selective Synthesis of Functionalized Tertiary Silanes by Diastereoselective Rearrangement—Addition.

Abstract

Treatment of hydroxy-substituted silyl-epoxides with Grignard reagents induces a 1,2-carbon shift to reveal α-silyl aldehydes, which are trapped by highly diastereoselective addition reactions of the Grignard reagent. The starting epoxides are readily accessible from propargylic alcohols by regioand diastereoselective hydrosilylation and epoxidation reactions. In addition to providing functionalized tertiary silane products, the method is shown to offer a tertiary olefin synthesis through chemo-and diastereoselective Peterson elimination of the product tertiary silane diols.Organosilicon compounds play an increasing role in organic synthesis wherein the silyl group serves as a sterically demanding directing group, 1,2 as a placeholder for oxygenation though Tamao-Fleming oxidation, 3 as an organometallic species for transition-metal catalyzed reaction, 4 or as a temporary, "traceless" tether for intramolecular reactions. 5 Additionally, allylic silanes are mild, stable nucleophiles. 2 However, in many respects methodology for the incorporation of silicon into complex targets lags behind the utility of such products. Most traditionally, reactive organometallic species are trapped with silyl chlorides. However, this approach negates the benefits of functional-group tolerance available to organosilicon-based routes. In addition, the generation of reactive organometallics such as Grignard reagents may be impossible in a congested, densely functionalized target. Other important routes, such as hydrosilylation, can be robust methods for primary alkyl 6 and vinylsilanes. 6,7 However, they are not generally compatible with the synthesis of highly congested silanes.We have examined the hydrosilylation of alkynes catalyzed by the ruthenium complex [Cp*Ru (MeCN) 3 ]PF 6 . Reactions catalyzed by this complex afford clean trans addition of a silane molecule to internal alkynes. A productive use of this method has been the hydrosilylation of propargylic alcohols, where (Z)-β-silyl allylic alcohols are formed selectively. 8 The placement of the silyl group offers the opportunity for diastereoselective epoxidation of the vinylsilane, 9 which can be further elaborated through silane oxidation (Scheme 1).We are interested in investigating other methods for the elaboration of the silylepoxide scaffold. Since allylic epoxides in general have a robust chemistry of selective ring-opening reactions, 10 we examined the possibility of selectively adding nucleophiles to silylepoxide 3 to afford bmtrost@stanford.edu.