Catalytic asymmetric cyanosilylation of ketones with chiral Lewis base.
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.
Tian
Shi-Kai
SK
Department of Chemistry, Brandeis University, Waltham, MA 02454-9110, USA.
Hong
Ran
R
Deng
Li
L
D000080:Acetals / Q000737:chemistry; D000605:Amino Alcohols / Q000138:chemical synthesis; D002930:Cinchona Alkaloids / Q000737:chemistry*; D003486:Cyanides / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D013237:Stereoisomerism; D014297:Trimethylsilyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D000080:Acetals; D000605:Amino Alcohols; D002930:Cinchona Alkaloids; D003486:Cyanides; D007659:Ketones; D014297:Trimethylsilyl Compounds; C058010:trimethylsilyl cyanide