An Organocatalytic Asymmetric Synthesis of Chiral β,β-Diaryl-α-amino Acids via Addition of Azlactones to In Situ Generated para-Quinone Methides.

An organocatalytic intermolecular C-C bond formation process leading to the efficient synthesis of chiral β,β-diaryl-α-amino acid derivatives is described. In the presence of a suitable chiral phosphoric acid catalyst, a range of para-hydroxybenzyl alcohols serve as efficient precursors to para-quinone methides and then react with azlactones in 1,6-conjugate addition reactions. The asymmetric control has been carefully optimized together with diastereocontrol enabled by identification of the reversible feature of the C-C bond formation and subsequent inhibition by protection of the free hydroxy group in one pot. Compared with previous approaches, including those with pre-synthesized para-quinone methides, this protocol provides an alternative and complementary step- and pot-economical approach for the synthesis of chiral β,β-diaryl-α-amino acid derivatives.