Chemoselective α-Alkylation and α-Olefination of Arylacetonitriles with Alcohols via Iron-Catalyzed Borrowing Hydrogen and Dehydrogenative Coupling.

Abstract

α-Alkyl and α-olefin nitriles are very important for organic synthesis and medicinal chemistry. However, different types of catalysts are employed to achieve either α-alkylation of nitriles by borrowing hydrogen or α-olefination by dehydrogenative coupling methods. Designing and developing high-performance earth-abundant catalysts that can procure different products from the same starting materials remain a great challenge. Herein, we report an iron(0) catalyst system that achieves chemoselectivity between borrowing hydrogen and dehydrogenative coupling protocols by simply changing the base. A broad range of nitriles and alcohols, including benzylic, linear aliphatic, cycloaliphatic, heterocyclic, and allylic alcohols, were selectively and efficiently converted to the corresponding products. Mechanistic studies reveal that the reaction mechanism proceeds through a dehydrogenative pathway. This iron catalytic protocol is environmentally benign and atom-efficient with the liberation of H2 and H2O as green byproducts.