Iron-Catalyzed Ligand Free α-Alkylation of Methylene Ketones and β-Alkylation of Secondary Alcohols Using Primary Alcohols.

Abstract

Herein, we demonstrate a general and broadly applicable catalytic cross coupling of methylene ketones and secondary alcohols with a series of primary alcohols to disubstituted branched ketones. A simple and nonprecious Fe2(CO)9 catalyst enables one-pot oxidations of both primary and secondary alcohols to a range of branched gem-bis(alkyl) ketones. A number of bond activations and formations selectively occurred in one pot to provide the ketone products. Coupling reactions can be performed in gram scale and successfully applied in the synthesis of an Alzehimer's drug. Alkylation of a steroid hormone can be achieved. A single catalyst enables sequential one-pot double alkylation to bis-hetero aryl ketones using two different alcohols. Preliminary mechanistic studies using an IR probe, deuterium labeling, and kinetic experiments established the participation of a borrowing-hydrogen process using Fe catalyst, and the reaction produces H2 and H2O as byproducts.