Novel and practical asymmetric synthesis of β2,3-amino esters using asymmetric Michael addition of chiral amine

Abstract A practical method for the synthesis of chiral β 2,3 -amino esters having various substituents was developed, which is characterized by an asymmetric Michael addition reaction of a chiral lithium amide with trisubstituted ( E )-α,β-unsaturated esters. We found that a highly face-selective protonation occurred by the quick addition of water to the enolate intermediate derived from the Michael addition reaction to afford N -protected β 2,3 -amino esters in moderate to excellent yields. This finding was made possible by the facile preparation of geometrically pure trisubstituted ( E )-α,β-unsaturated esters, which was established recently by our group. The subsequent deprotection of the amino group in the Michael adduct by using N -iodosuccinimide (NIS) efficiently provided β 2,3 -amino esters having various substituents.