Brønsted acid catalyzed formal insertion of isocyanides into a C-O bond of acetals.

The Bronsted acid catalyzed formal insertion of an isocyanideinto a C−O bond of an acetal is described. A diverse array of acyclic and cyclic acetals can be applied to the catalytic insertion to form α-alkoxy imidates. Functional groups, such as nitro, cyano, halogen, ester, and alkoxy groups, are tolerant to the reaction conditions employed. The course of the reaction is highly dependent on the structure of the isocyanide. The use of an electron-deficientaryl isocyanide, such as 2c and 2d, is required to selectively obtain the monoinsertion product. When aryl isocyanidescontaining alkyl substituents, such as 2a and 2b, are employed, two molecules of the isocyanideare incorporated, and the double-insertion product is obtained. The reaction of tert-octyl isocyanidealso induces a double incorporation, but the subsequent acid-mediated fragmentation leads to the 2-alkoxy imidoyl cyanide. The monoinsertion products, α-alkoxy imidates, can readily be hydrolyzed to α-alkoxy esters, realizing the formal carb...