Dramatic Ligand Effect in Catalytic Asymmetric Reductive Aldol Reaction of Allenic Esters to Ketones

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Abstract
A general catalytic asymmetric reductive aldol reaction of allenic esters to ketones is described. Two distinct constitutional isomers were selectively produced depending on the reaction conditions. A combination of CuOAc/(R)-DTBM-SEGPHOS/PCy3 as the catalyst predominantly produced γ-cis-products in high yield with excellent enantioselectivity (up to 99% ee). The reaction was applicable to both aromatic and aliphatic ketones, including unsaturated ketones. On the other hand, CuF−Taniaphos complexes produced α-aldol products with high diastereo- and enantioselectivity (up to 84% ee). The new Taniaphos derivative L3, containing di(3,5-xylyl)phosphine and morpholine units, produced optimum results in the α-selective reaction. The products are versatile chiral building blocks in organic synthesis. Furthermore, the basic reaction pattern (i.e., conjugate addition−aldol reaction) was extended to a catalytic enantioselective alkylative aldol reaction to ketones using dialkylzinc reagents as the initiator.