Asymmetric amination of α,α-dialkyl substituted aldehydes catalyzed by a simple chiral primary amino acid and its application to the preparation of a S1P1 agonist

Abstract

The chiral catalytic amination of an α,α-dialkyl substituted aldehyde usually proceeds with low enantioselectivity. We selected naphthyl-L-alanine as the catalyst and observed improved enantioselectivity for the amination. Using this method, racemic α-methyl-α-benzyloxypropanal was aminated to give chiral serine derivatives in 74% ee, which was further increased to >99% ee after recrystallization. Moreover, we also successfully synthesized a chiral phosphonium salt 9 for the preparation of one α-substituted alaninol compound 14 as an S1P₁ agonist in high overall yield.