Long-Range Diastereoselectivity in an Ugi Reaction: Stereocontrolled and Diversity-Oriented Synthesis of Tetrahydrobenzoxazepines

Salicylaldehydes and protected 1,2-amino alcohols have been convergently converted into a series of 2,3-dihydrobenzo[f][1,4]oxazepines, which undergo an Ugi–Joullié multicomponent reaction with unusual long-range diastereoselectivity. This protocol allows the diastereoselective preparation, in only two steps, of a series of drug-like tetrahydrobenzo[f][1,4]oxazepines, with the combinatorial introduction of four diversity points. The possibility of obtaining these compounds in enantiomerically pure form was also demonstrated