Advancing the Reactivity of the Isocyanide Functionality

Isocyanides are powerful building blocks whose unique reactivity has been harnessed in an extraordinary array of multi-component reactions, insertions, radical additions, and cationic cascades. The extraordinary reactivity emanates from the highly unusual electronic structure of the divalent isocyanide carbon that has both nucleophilic and electrophilic character that serves to initiate most reactions of isocyanides. In contrast, there is a serious dearth of reactions available for manipulating the carbon scaffold of isocyanides that limits the synthetic potential of isocyanoalkanes and isocyanoalkenes. We have developed several different methods to manipulate the carbon scaffold of isocyanides ranging from the use of Asmic to address the long-standing difficulty of simple alkylations to the first conjugate additions to unactivated isocyanoalkenes. The synthesis and reactivity of isocyanides is surveyed with a focus on accessing complex nitrogenous scaffolds.