Catalytic Cross-Coupling of Secondary Alcohols

Herein, an unprecedented ruthenium­(II)
catalyzed direct cross-coupling
of two different secondary alcohols to β-disubstituted ketones
is reported. Cyclic, acylic, symmetrical, and unsymmetrical secondary
alcohols are selectively coupled with aromatic benzylic secondary
alcohols to provide ketone products. A single catalyst oxidizes both
secondary alcohols to provide selectively β-disubstituted ketones
to broaden the scope of this catalytic protocol. Number of bond activation
and bond formation reactions occur in selective sequence via amine–amide
metal–ligand cooperation operative in Ru-MACHO catalyst. The
product-induced diastereoselectivity was also observed. Kinetic and
deuterium labeling experiments suggested that the aliphatic secondary
alcohols undergo oxidation reaction faster than benzylic secondary
alcohols, selectively assimilating to provide the cross-coupled products.
Reactions are sensitive to steric hindrance. This new C–C bond
forming methodology requires low catalyst load and catalytic amount
of base. Notably, the reaction produces H2 and H2O as the only byproducts making the protocol greener, atom economical
and environmentally benign.