Enantioconvergent Hydrobenzylation of Racemic Allylic Alcohols with Aryl Hydrazones via Bifunctional Ruthenium Catalysis

The use of hydrazones as carbanion equivalents for carbon–carbon
bond formation reactions has emerged as a versatile tool for organic
synthesis. However, the enantioselective formation of carbon–carbon
bonds with hydrazones has been underdeveloped. We have developed a
Ru-catalyzed enantioconvergent hydrobenzylation of racemic allylic
alcohols using aryl hydrazones as latent alkyl nucleophiles. The reaction
produces enantioenriched products with two remote chiral centers,
achieving high diastereoselectivities (up to 20:1 dr) and excellent
enantioselectivities (99% ee in most cases). Notably, the alkyl source
originates from the electrophilic sp2 carbons of hydrazones,
which are readily prepared from various aldehydes and depart from
the most often employed alkyl nucleophiles derived from organometallic
sp3 carbons, and the reaction releases harmless N2 as the sole byproduct. Mechanistic investigations suggest a sequential
dehydrogenation/conjugate addition/reduction pathway with a single
Ru complex catalyzing both the borrowing hydrogen and hydrazone conjugate
addition cycles while simultaneously controlling the stereoselectivities
of both chiral centers. DFT studies reveal that the Ru complex acts
as a metal–ligand bifunctional catalyst, activating the hydrazones,
reversing the CN bond polarity, and facilitating the conjugate
addition. The key transition state of the bond formation step features
the attack of the activated hydrazone on an α,β-unsaturated
ketone in an outer-sphere manner, offering a new catalytic mode for
hydrazone chemistry.