Quick Installation of a 1,4-Difunctionality via Regioselective Nickel-Catalyzed Reductive Coupling of Ynoates and Aldehydes

The development of efficient methods for the synthesis of molecules with 1,4-difunctionalities has been a dire need of the synthetic community. In this work, intermolecular reductive coupling of ynoates and aldehydes (in the presence of a silane) has been accomplished for the first time using catalytic amounts of Ni(COD)(2), an N-heterocyclic carbene ligand, and PPh3. High regioselectivity has been demonstrated for the multicomponent coupling reactions, and more than a dozen invaluable silyl-protected gamma-hydrox-alpha,beta-enoates have been synthesized. This methodology provides a quick entry to many other 1,4-difunctional compounds and oxygen-containing five-membered rings. The intermediacy of metallacycles in the catalytic process has been established by deuterium-labeling experiments.