MAC-TBS Reagent Usable for Three Component Coupling Reactions

(tert-Butyldimethylsilyloxy)malononitrile (1), developed by Nemoto et al., is called a MAC (Masked Acyl Cyanide) reagent.¹⁾ 1 forms an anion species 2 by the treatment of a base and 2 acts as an acyl anion equivalent. By taking advantage of this property, 1 can be applied to three component coupling reactions with electrophiles and nucleophiles.^2,3) For example, 2 reacts with aldehydes to form an acyl cyanide intermediate 3. Sequential addition of amines as nucleophiles gives α-siloxyamides as three component adducts.³⁾ In these sequential steps, three components can be added in one-portion to the flask. This reaction can be applied to electrophiles such as aldehydes, ketones and imines and nucleophiles such as alcohols and amines. Furthermore, this reaction can afford Weinreb amides when using DMHA·HCl.