Stereoselective Michael addition of benzylamines to homochiral methylenebutanedioates

Abstract

The Michael addition of benzylamine to the homochiral methylenebutanedioate 10 gave an adduct 11 in good yield with high stereoselectivity. By performing the reaction in methanol the (2R,3R) diastereoisomer 11 was obtained in 88% de, which was increased to 98% de after recrystallisation of the primary amine derivative 13. The ratio of diastereoisomers was reversed by performing the reaction in aprotic solvents, with the (2R,3S) diastereoisomer 12 being obtained in 40% de in tetrahydrofuran. The Michael adduct 11 is formed under kinetic control. The primary amine 15 is a key intermediate in the synthesis of novel matrix metalloproteinase inhibitors.