Enantioselective Protonation by Cinchona Alkaloids via Phospha-Brook Rearrangement

Significance

Hayashi and Nakamura report an enantioselective protonation reaction of ester enolates which are generated after hydrophospho­nylation to A and phospha-Brook rearrangement. In general, the phospha-Brook rearrangement has been considered a side reaction of hydrophosphonylation of carbonyl compounds (Chem. Sci. 2010, 1, 488). Here, the authors use this transformation to generate an enolate species which can be protonated by a chiral base. Quinine and quinidine show remarkable catalytic efficiency even with 2 mol% catalyst loading (96:4 er). The protection of the 9-hydroxy group of quinidine resulted in diminished enantioselectivity due to the absence of a hydrogen-bonding interaction.