Kinetic resolution by lithiation: highly enantioselective synthesis of substituted dihydrobenzoxazines and tetrahydroquinoxalines

Kinetic resolution provided a highly enantioselective method to access a range of 3-aryl-3,4-dihydro-2H-1,4-benzoxazines using n-butyllithium and the chiral ligand sparteine. The enantioenrichment remained high on removing the tert-butoxycarbonyl (Boc) protecting group. The intermediate organolithium undergoes ring-opening to an enamine. The kinetic resolution was extended to give enantiomerically enriched substituted 1,2,3,4-tetrahydroquinoxalines and was applied to a synthesis of an analog of the antibiotic levofloxacin that was screened for its activity against the human pathogen Streptococcus pneumoniae.