Development of New Synthetic Reactions Featuring Tandem Carbon-Carbon Bond Formation

Abstract

Development of new synthetic reactions that feature a tandem process triggered by Brook rearrangement, a C-to-O 1,2-anionic shift of a silyl group, will be discussed. A basic motif for the strategy is the generation of an alpha-siloxy carbanion by the reaction of acylsilanes with ketone enolates and then trapping the anions by intra- and inter-molecular electrophiles. For example, the reaction of benzoyltrimethylsilane with lithium enolates of methyl ketones produced 1,2-cyclopropanediols via Brook rearrangement of the initial 1,2-adduct and subsequent internal aldol reaction. This concept was applied to the synthesis of five- and seven-membered carbocycles using the reaction of acryloylsilanes with enolates of alkyl and alkenyl methyl ketones, respectively. Furthermore, we found that the use of enolate of 2-cycloheptenone instead of the enolates of alkenyl methyl ketone as the four-carbon unit in the [3+4] annulation produces bicyclo[3.3.2]- decenone derivatives, in which the two-atom internal tether could be cleaved to give the cis-3,4,8-trisubstituted cyclooctenone enol silyl ethers stereoselectively. The alpha-siloxy carbanions can be also generated by an gamma-anion-induced ring cleavage of alpha,beta-epoxysilanes. Thus, O-silyl cyanohydrins of beta-silyl-alpha,beta-epoxyaldehyde can function as a highly functionalized homoenolate equivalent via a tandem sequence involving base-promoted ring opening, Brook rearrangement, and alkylation at the allylic position. Based on these results, we developed several new synthetically useful reactions in which three methods for the generation of a carbanion at the gamma-position, i.e., deprotonation, reaction of acylsilanes with a nucleophile followed by Brook rearrangement, and a conjugate addition of a nucleophile to an enoate system bearing an epoxysilane moiety at the alpha-position, were used.