Small Molecule Drug Discovery, Bristol Myers Squibb, Cambridge, Massachusetts 02142, United States.
Chemical Process Development, Bristol Myers Squibb, New Brunswick, New Jersey 08903, United States.
Org Lett. 2023 Jun 16;25(23):4219-4224. doi: 10.1021/acs.orglett.3c01478. Epub 2023 Jun 6.
A decarboxylative C(sp)-C(sp) cross-coupling reaction of α-oxy carboxylic acids using dual nickel/photoredox catalysis has been developed for the synthesis of complex morpholines and other saturated heterocycles, affording direct entry to scaffolds of interest in drug discovery. This chemistry can be applied to the coupling of an array of (hetero)aryl halides and α-heteroatom acids, providing C(sp)-C(sp)-coupled products in modest to excellent yields and enabling access to intermediates that can be further derivatized to multivector architectures.
发展了一种使用双镍/光氧化还原催化的α-氧羧酸的脱羧 C(sp)-C(sp)交叉偶联反应，用于合成复杂的吗啉和其他饱和杂环，为药物发现中感兴趣的支架提供了直接途径。这种化学方法可以应用于一系列（杂）芳基卤化物和α-杂原子酸的偶联，以中等至优异的收率提供 C(sp)-C(sp)偶联产物，并能够获得可进一步衍生为多向量结构的中间体。
