ZrH-Catalyzed Semi-Reduction of Esters Enabled by an Imine/Enamine Trap

Semi-reductive transformations of esters remains an underdeveloped but valuable class of functional group interconversions. For example, few strategies exist for the catalytic partial reduction of esters to aldehydes, and the direct catalytic semi-reductive imination/enamination of esters is absent from synthetic strategy. Here, we describe the development of a highly selective method for the interconversion of esters to imines, enamines, aldehydes or amines through an amine-intercepted ZrH-catalyzed reduction. This protocol employs Cp2ZrCl2 as an inexpensive catalyst in combination with hydrosilanes and simple unprotected amines. The in situ formation of imines and enamines effectively preserves an aldehyde oxidation level throughout the course of the reaction. A variety of aryl and aliphatic esters are directly transformed to imines and enamines in up to 99% yield or aldehydes in up to 84% yield, with little-to-no reduction to the corresponding alcohols. The utility of this method for the efficient preparation of nitrogen-containing products is also presented, including single-flask multicomponent reactions and the direct reductive amination of esters. These findings further demonstrate the utility of oxophilicity-driven ZrH catalysis for unconventional chemical transformations.