Efficient and stereoselective one-pot synthesis of benzo[ b]oxazolo[3,4- d][1,4]oxazin-1-ones

Hongyi Zhao; Wenting Zhao; Shihao Cheng; Haijia Lu; Dongfeng Zhang; Haihong Huang

doi:10.1039/d0ra04104a

Efficient and stereoselective one-pot synthesis of benzo[ b]oxazolo[3,4- d][1,4]oxazin-1-ones

RSC Adv. 2020 Jun 23;10(40):24037-24044. doi: 10.1039/d0ra04104a. eCollection 2020 Jun 19.

Authors

Hongyi Zhao^{1

2}, Wenting Zhao^{1

2}, Shihao Cheng^{1

2}, Haijia Lu^{1

2}, Dongfeng Zhang^{1

2}, Haihong Huang^{1

2}

Affiliations

¹ Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences 1 Xian Nong Tan Street Beijing 100050 P. R. China zdf@imm.ac.cn joyce@imm.ac.cn.
² Chinese Academy of Medical Sciences Key Laboratory of Anti-DR TB Innovative Drug Research, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences 1 Xian Nong Tan Street Beijing 100050 P. R. China.

Abstract

An efficient and mild one-pot convergent synthesis protocol has been developed for benzo[b]oxazolo[3,4-d][1,4]oxazin-1-one derivatives through the Mitsunobu reaction and sequential cyclization. Various tricyclic fused benzoxazinyl-oxazolidinones (20 examples) were obtained in good to excellent yields and high enantioselectivities with facile operation. Furthermore, four stereoisomers were afforded respectively in high ee values (>97.8%) via using different chiral 2,3-epoxy-4-trityloxybutanol. This methodology has been applied to the synthesis of key intermediates of drug candidates.