Metal-free and enantioselective synthesis of 1,4-benzoxazepines from para-quinone methide derivatives and & alpha;-bromohydroxamates

A sequential asymmetric conjugate addition/cyclisation of & alpha;-bromohydroxamates with para-quinone methide derivatives has been developed, which provides enantioenriched 1,4-benzoxazepines in generally high yields (up to 95%) and good enantioselectivities (up to 97 : 3 er). This protocol not only offers a novel and straightforward strategy for constructing chiral 1,4-benzoxazepines, but also demonstrates the potential of & alpha;-bromohydroxamates as three-atom synthons in asymmetric cyclisation reactions.

Automated summary

A sequential asymmetric conjugate addition/cyclisation of α-bromohydroxamates with para-quinone methide derivatives has been developed, providing enantioenriched 1,4-benzoxazepines in high yields (up to 95%) and good enantioselectivities (up to 97:3 er). This method offers a novel and straightforward strategy for constructing chiral 1,4-benzoxazepines, and demonstrates the potential of α-bromohydroxamates as three-atom synthons in asymmetric cyclisation reactions.