Abstract

Chiral N,O-heterocycles were synthesized in high yields and excellent enantioselectivity up to 97% ee via iridium-catalysed intramolecular allylic substitution with nucleophilic attack by the amide oxygen atom. The resulting benzoxazine derivatives were further transformed into challenging chiral N,O-ketals bearing both a tertiary and a quaternary center with excellent diastereoselectivities.

Highlights

  • Chiral N,O-heterocycles are important structural motifs found in a variety of natural products which exhibit signi cant biological activities including anti-tumor, antifungal and antibacterial properties.[1]

  • Oxazolines, oxazines, benzoxazines and their derivatives are of particular importance

  • Efavirenz (Sustiva), which features a 4H-3,1-benzoxazin-2-one core, is a non-nucleoside reverse transcriptase inhibitor and is used for the treatment of human immunode ciency virus (HIV) type 1.2 4H-3,1-benzoxazin-4-one derivatives are able to inhibit C1r serine protease.2b N,Oheterocycles play a prominent role in asymmetric synthesis as they are core structures of several chiral ligands used in asymmetric catalysis.[3]

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Summary

Introduction

Chiral N,O-heterocycles are important structural motifs found in a variety of natural products which exhibit signi cant biological activities including anti-tumor, antifungal and antibacterial properties.[1]. We envisioned that reversing the selectivity of the ambidentate amide nucleophile in the iridium-catalysed intramolecular AAS could provide a versatile method to access chiral oxazolines, oxazines and benzoxazines (Scheme 1b). >95 a Reaction conditions: 5 mol % [Ir(cod)Cl]2, 10 mol % of ligand, 0.2 mmol of 1a, 0.2 mmol of base in 2.0 mL THF (0.1 M) unless otherwise noted.

Results
Conclusion

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