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

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posted on 04.06.2018 by Abhijit Mal, Imtiyaz Ahmad Wani, Gaurav Goswami, Manas K. Ghorai
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.