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

• Published in: Chemistry, an Asian journal an Asian journal, 2018-09, Vol.13 (17), p.2440-2444
• Main Authors: Yan, Jiyao, Chen, Min, Sung, Herman H‐Y., Williams, Ian D., Sun, Jianwei
• Format: Article
• Language: English
• Subjects: Alcohols; Amino acids; Bonding; Chemistry; chirality; Derivatives; organocatalysis; Phosphoric acid; quinone methides; Synthesis; synthetic methods
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.201800569

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. An organocatalytic intermolecular C−C bond formation process leading to the efficient synthesis of chiral β,β‐diaryl‐α‐amino acid derivatives is developed. 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. Good to excellent asymmetric control was shown and diastereocontrol was enabled by inhibiting the reversibility of the C−C bond‐formation step.