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

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.