A Novel Synthesis of Densely Functionalized 3,4-β-Lactam Fused 1,4-Oxazepane via Tandem-7-exo-trig Intramolecular Oxa-Michael Reaction

Abstract: A versatile and chemoselective intramolecular oxa-Michael reaction of α,β-unsaturated ester tethered on a prebuilt stereodefined β-lactam ring in a novel synthesis of a bicyclic scaffold of 1,4-oxazepane embedded on the β-lactam ring has been developed. The tandem process involves a successive deprotection of the O-isopropylidene group, followed by the chemoselective nucleophilic conjugate addition of 2° hydroxy functionalities of vic diol to the unsaturated esters preferentially 7-exo-trig mode of ring closure. The developed protocol proceeded well under mild alkaline conditions and furnished a novel scaffold of bicyclic β-lactam featuring 1,4-oxazepane rings in a high chemoselective fashion.[Equation not available: see fulltext.]