Regio‐ and Diastereoselective Functionalization of 3‐Amino‐hexahydrooxazoninones

Abstract

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.