Asymmetric 1,6-Conjugate Addition of para-Quinone Methides for the Synthesis of Chiral β,β-Diaryl-α-Hydroxy Ketones

A direct asymmetric 1,6-conjugated addition of alpha-hydroxy ketone to para-quinone methides has been developed. It is an efficient approach to the synthesis of chiral beta,beta-diaryl-alpha-hydroxy ketones. The reaction runs smoothly in the presence of ZnEt2 and nonracemic bis(diarylhydroxymethylpyrrolidinylmethyl)phenols (ProPhenols), and the desired products are obtained in good yields (up to 88%) and with high stereoselectivity (up to >99% ee and up to >99:1 dr). This reaction also can be run on a gram scale without impacting its enantioselectivity.