Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 2030, 128 43 Prague, Czech Republic.
Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, 160 00 Prague, Czech Republic.
Org Lett. 2021 Dec 17;23(24):9376-9381. doi: 10.1021/acs.orglett.1c03419. Epub 2021 Nov 24.
Herein, we describe a versatile transition metal/oxidant free synthesis of the chiral 2-1,4-benzoxazines through chiral phosphoric acid (CPA) catalyzed enantioselective desymmetrization 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 2-1,4-benzoxazine synthetic strategies but also provides access to key intermediates of therapeutic candidates, i.e., prostaglandin D2 receptor antagonist and M1 positive allosteric modulator (PAM) compound VU0486846.
在这里，我们描述了一种通过手性磷酸（CPA）催化前手性环氧乙烷（30 个实例）的对映选择性去对称化，在温和的反应条件下，通过过渡金属/氧化剂自由合成手性 2-1,4-苯并恶嗪的通用方法，产率高达 99%，对映选择性为 99%。所报道的策略不仅补充了传统的 2-1,4-苯并恶嗪合成策略，而且还提供了治疗候选物的关键中间体，即前列腺素 D2 受体拮抗剂和 M1 正变构调节剂（PAM）化合物 VU0486846。
