Me₂(CH₂Cl)SiCN: Bifunctional Cyanating Reagent for the Synthesis of Tertiary Alcohols with a Chloromethyl Ketone Moiety via Ketone Cyanosilylation

Abstract

We report a novel bifunctional cyanating reagent, Me2(CH2Cl)SiCN, which paves the way to a one-pot sequential synthesis of tertiary alcohols featuring a chloromethyl ketone moiety via enantioselective ketone cyanosilylation. This method contributes to gram-scale enantioselective total synthesis of the aggregation pheromone of the Colorado potato beetle, (S)-CPB.

Cyanosilylation by Compounds with Main-Group Elements: An Odyssey

“…In 2016, the same group has utilized a unique bifunctional cyanating reagent, Me 2 (CH 2 Cl)SiCN and catalyst 16 in the presence of a phosphorane for the synthesis of tertiary alcohols via catalytic enantioselective cyanosilylation of a chloromethyl ketone moiety ( Scheme 6 ). 18 The bifunctional reagent, Me 2 (CH 2 Cl)SiCN exhibited improved results in cyanosilylation than Me 3 SiCN.…”

Recent Advances in Applying Carbonyl‐stabilized Phosphorus Ylides for Catalysis

“…Taking advantage of the activation of ( R,R )‐(salen)AlCl by phosphorane 23 e , Zhou et al. further developed a highly enantioselective cyanosilylation of aliphatic or α,β‐unsaturated ketones using a newly designed bifunctional cyanating reagent Me 2 (CH 2 Cl)SiCN 30 , which afforded the desired cyanohydrins 31 with 72–99 % yields and 83–98 % ee values (Scheme 10, eq 1) [31] . Without the assistance of phosphorane 23 e , the reaction failed to take place.…”

“…[32] More importantly, an unprecedented one-pot synthesis of tertiary alcohols 34 featuring a chloromethyl ketone functionality through a tandem ketone cyanosilylation/chloromethyl transfer sequence was established by the same group (Scheme 11). [31] In the presence of 2.5 mol % (R,R)-(salen)AlCl and phosphorane 23 e, various cyanohydrin trimethylsilyl ethers 31 were generated effectively. Subsequently, upon treatment of 31 with LDA led to an intermediate I, and provided the desired tertiary alcohols 34 after hydrolysis.…”

Recent Advances in Catalytic Asymmetric Synthesis of Tertiary Alcohols via Nucleophilic Addition to Ketones

“…Soon after, Zhou and co‐workers devised a bifunctional cyanating reagent, Me 2 (CH 2 Cl)SiCN, for the asymmetric cyanosilylation of alkyl, aryl, vinyl and ethynyl ketones catalyzed by the chiral (salen)AlCl complex ( R , R )‐ 176 (10 mol%) and phosphorane 177d (10 mol%) (Scheme ) . Noticeably, in this reaction, the Lewis base additive Ph 3 PO was not required when using Et 2 O as the solvent.…”