A facile synthesis of α,ß-unsaturated imines via palladium-catalyzed dehydrogenation.

ABSTRACT

The dehydrogenation adjacent to an electron-withdrawing group provides an efficient access to α,ß-unsaturated compounds that serving as versatile synthons in organic chemistry. However, the α,ß-desaturation of aliphatic imines has hitherto proven to be challenging due to easy hydrolysis and preferential dimerization. Herein, by employing a pre-fluorination and palladium-catalyzed dehydrogenation reaction sequence, the abundant simple aliphatic amides are amendable to the rapid construction of complex molecular architectures to produce α,ß-unsaturated imines. Mechanistic investigations reveal a Pd(0)/Pd(II) catalytic cycle involving oxidative H-F elimination of N-fluoroamide followed by a smooth α,ß-desaturation of the in-situ generated aliphatic imine intermediate. This protocol exhibits excellent functional group tolerance, and even the carbonyl groups are compatible without any competing dehydrogenation, allowing for late-stage functionalization of complex bioactive molecules. The synthetic utility of this transformation has been further demonstrated by a diversity-oriented derivatization and a concise formal synthesis of (±)-alloyohimbane.