Catalytic Asymmetric Cyanosilylation of Ketones with Chiral Lewis Base

Abstract

The development of broadly applicable and practical catalytic approaches for the enantioselective creation of quaternary stereocenters remains a highly desirable yet challenging goal. In this Communication, we describe a highly enantioselective cyanosilylation of acetal ketones (alpha,alpha-dialkoxy ketones) catalyzed by modified cinchona alkaloids. This reaction is the first highly enantioselective cyanosilylation of ketones catalyzed by an organic chiral Lewis base and is found to be highly efficient with acetal ketones bearing a broad range of alkyl, aryl, alkenyl, and alkynyl substituents. This new catalytic asymmetric reaction, coupled with the versatility of the acetal functionality, provides a broadly useful synthetic method for chiral building blocks bearing quaternary stereocenters. Acetal ketones, readily accessible but previously unexplored in asymmetric synthesis, demonstrate unusual reactivity and selectivity toward the nucleophilic cyanosilylation, thereby suggesting that they may be interesting substrates for other catalytic enantioselective reactions.

Lewis Base Catalysis in Organic Synthesis

“…[266,267] With a stannylated cinchonine catalyst 214, good yields and enantioselectivities are obtained, albeit with a rather high loading of the [266b] More recently, Deng and co-workers have employed Sharplesss dimeric cinchona alkaloids to effect a highly selective cyanosilylation. [268] However, the method is currently limited to the use of a,a-dialkoxy ketones. The mechanism of the reaction has yet to be clarified, but the intermediacy of either a hypervalent silicate or an ionized silyl cation-cyanide anion ion pair can be proposed.…”

A Simple and Straightforward Synthesis of Cinnamic acids and Ylidene Malononitriles via Knoevenagel Condensation Employing DABCO as Catalyst

“…DABCO and its analogues show high efficiency in MoritaBaylis-Hillman reactions [10] as well as cyanation of ketones [11]. It has also been employed as a catalyst for the substitution of chloropurine with alcohols [12], isothiocynation of amines, isoxazoline derivatives from activated primary nitro compounds and tertiary diamines, synthesis of naphthopyrans.…”

“…It has also been employed as a catalyst for the substitution of chloropurine with alcohols [12], isothiocynation of amines, isoxazoline derivatives from activated primary nitro compounds and tertiary diamines, synthesis of naphthopyrans. Recently DABCO was used in addition of selenosulfonates to α,β-unsaturated ketones and in Sonogashira coupling reaction [13].…”

Effective Activation of the Chiral Salen/Ti(OiPr)4 Catalyst with Achiral Phenolic N-Oxides as Additives in the Enantioselective Cyanosilylation of Ketones.

“…[4] Deng and co-workers have outlined a method for the addition of cyanide to ketones using cyanoformate and catalytic amounts of cinchona alkaloids. [5] Recently, Snapper and co-workers reported a new approach to asymmetric cy-ethers in 58−96% yields with 56−82% ee. Several factors concerning the reactivity and enantioselectivity have been discussed.…”