Synthesis of Nonracemic 1,4-Benzoxazines via Ring Opening/Cyclization of Activated Aziridines with 2‑Halophenols: Formal Synthesis of Levofloxacin

Novel 3,4-dihydro-1,4-benzoxazine
derivatives have been synthesized
by an efficient and simple method in excellent enantio- and diastereospecificity
(ee > 99%, de > 99%). The reaction proceeds via Lewis acid-catalyzed
SN2-type ring opening of activated aziridines with 2-halophenols
followed by Cu­(I)-catalyzed intramolecular C–N cyclization
in a stepwise fashion under one-pot conditions to furnish the 3,4-dihydro-1,4-benzoxazine
derivatives in excellent yields (up to 95%). The strategy offers a
short and efficient synthesis to (S)-3-methyl-1,4-benzoxazine
(S)-3v, a late stage intermediate in
the synthesis of levofloxacin.