Enantioselective Desymmetrization of 3-Substituted Oxetanes: An Efficient Access to Chiral 3,4-Dihydro-2H-1,4-benzoxazines

Herein, we describe a versatile transition metal/oxidant free synthesis of the chiral 2H-1,4-benzoxazines through chiral phosphoric acid (CPA) catalyzed enantioselective desym-metrization of prochiral oxetanes (30 examples) in up to 99% yield and 99% enantioselectivity under mild reaction conditions. The reported strategy not only complements the conventional 2H-1,4-benzoxazine synthetic strategies but also provides access to key intermediates of therapeutic candidates, i.e., prostaglandin D2 receptor antagonist and MI positive allosteric modulator (PAM) compound VU0486846.

Automated summary

The study presents a versatile method for the synthesis of chiral 2H-1,4-benzoxazines using chiral phosphoric acid catalysis, achieving high yields and enantioselectivity under mild conditions. This strategy expands on traditional methods and provides access to key intermediates for therapeutic candidates, such as prostaglandin D2 receptor antagonists and MI positive allosteric modulator (PAM) compound VU0486846.