Regio- and Diastereoselective Functionalization of 3-Amino-hexahydrooxazoninones

The regio- and diastereoselectivity of transformations of nine-membered lactams with a Z double bond in the cyclic tether towards building blocks for medicinal chemistry was evaluated. To this end, 3-aminohexahydrooxazoninones were synthesized using a standard ring-closing metathesis (RCM) approach of easily available O,N-bisallylated serine derivatives. The obtained Z double bond in the medium sized lactam was used as a handle to evaluate the stereoselectivity of electrophile induced transformations. It was shown that dibromination and electrophilic activation by NBS followed by attack of O-nucleophiles proceeded in a diastereoselective manner. Cyclization of obtained bromohydrins and face-selective epoxidation gave access to both diastereomers of the epoxidized lactams. Finally, a Heck-reaction of a bromobenzyl moiety at the lactam N-atom with the Z-double bond resulted in the diastereoselective formation of bicyclic bridged nine-membered lactams.