Stereodivergent access to all four stereoisomers of chiral tetrahydrobenzo[f] [1,4]oxazepines, through highly diastereoselective multicomponent Ugi-Joullié reaction

Abstract

Starting from easily accessible chiral enantiopure 1,2-amino alcohols and salicylaldehydes, a concise route to cyclic imines has been developed. These chiral cyclic imines undergo a highly diastereoselective Ugi-Joullié reaction to give trans tetrahydrobenzo[f][1,4]oxazepines with the introduction of up to 4 diversity inputs. The cis isomer may also be attained, thanks to a thermodynamically controlled base catalysed epimerization. Free secondary amines have been obtained using an unprecedented "removable" carboxylic acid.