Asymmetric Synthesis of β,β-Disubstituted Alanines via a Sequential C(sp2)–C(sp3) Cross-Coupling–Hydrogenation Strategy

We report the development of a sequential C(sp²)-C(sp³) Suzuki cross-coupling-asymmetric hydrogenation strategy which allows access to a diverse array of valuable β,β-disubstituted alanine derivatives. This synthesis exhibits broad functional group tolerance, and permits efficient access to β-aryl-β-alkyl, and the more rarely reported β,β-dialkyl Ala derivatives with high yield and excellent enantioselectivity. This transformation has been exhibited on decagram quantity, and can be used to generate Fmoc amino acid derivatives which are useful for SPPS.