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

Abstract

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.