The syn-selective conjugate addition of amines to enoates derived from d-mannitol

Abstract

The syn-selective conjugate addition of neat amines to enoates Z-1 and E-1, prepared from d-(+)-mannitol, is reported. The reactions with benzyl and allylamine 2a,d at −50°C or 2e at −25°C in the absence of a solvent led to syn-adducts in moderate to good chemical yields and good syn/anti ratios, and were accelerated in the presence of DBU. Enoate Z-1 was more reactive than E-1, leading to products with better syn-selectivity. The syn-selectivity slightly decreased for reactions at rt. The reaction of both enoates with primary amines 2c,d (Ph changed by 2- and 3-pyridyl) only occurred at rt, leading to adducts in good chemical yields and with moderate to good syn-selectivities. Secondary acyclic amine 2f showed very low reactivity (rt, DBU, several hours) and led to the adduct in moderate chemical yields and with low syn-stereoselectivity while higher reactivity and moderated yields and syn-selectivities were observed for cyclic secondary amines 2g–i.