摘要：Rajender Nallagonda,* Rachel Quan, Lauren Grant, ChristineJorge, Shiuhang Yip, Dauh-Rurng Wu,T. G. Murali Dhar, James Kempson,Arvi

转自：康龙化成

Unveiling the StereoselectivityAspects of Metallaphotoredox Decarboxylative Arylation

Rajender Nallagonda,* Rachel Quan, Lauren Grant, ChristineJorge, Shiuhang Yip, Dauh-Rurng Wu, T. G. Murali Dhar, James Kempson,Arvind Mathur, and Martins S. Oderinde*

Small Molecule Discovery Chemistry,Bristol Myers Squibb Research and Early Development, Princeton, New Jersey08543, United States

—ACS Catal. 2024, 14, 13439−13450.

Recommended by Shi Li_MOC

KEYWORDS:photocatalysis (反应类型),decarboxylative arylation (反应类型), C(sp2)-C(sp3) (成键类型), carboxylic acid (原料),(hetero)aryl halide (原料), cycloalkylarene (产物),NiCl2(dme)(催化剂)

ABSTRACT: Martins S. Oderinde et al unveil the diastereoselectivity aspects of metallaphotoredox decarboxylative arylation of substituted cyclic carboxylic acids. Throughjudicious screening of conditions, ligands, and additives, photoredox-promotedNi-catalyzed decarboxylative arylation was rendered highly diastereoselective,enabling modular access to complex cyclic architectures. The reaction toleratesvarious functional groups, including free alcohols and basic amines. Finally,to demonstrate the simplifying power of this coupling approach, the authoremployed it to truncate the synthesis of Iptacopan (LNP023), a recently FDA-approved drugfor treating Paroxysmal nocturnal hemoglobinuria (PNH) disorder in adults, fromthe previously reported 12-steps (racemic route) to 4-steps (enantioselectiveroute).

Background and this work

Substrate scope (selected)

MartinsS. Oderinde etal developed stereoselective metallaphotoredox decarboxylative arylation reactions of various substituted cyclic carboxylicacids. Electron-rich 4,4’-dimethoxy-2,2’- bipyridine ligand and simplephthalimide additive were identified as critical reaction parameters forpromoting the Ni-metallaphotoredox decarboxylative arylation in a diastereoselective fashion. Thiswork represents the first systematic studies on the diastereoselectivity aspects of metallaphotoredox decarboxylative arylation. The stereoselectivity is generally high for 6, 5, 4,and 3-membered rings with a substituent at the 2-position. 1,3- and1,4-substituted 6-membered cyclic carboxylic acids also gave good product d.r.5-membered cyclic carboxylic acids with a substituent at the 3-positiondelivered moderate to good product d.r. This metallaphotoredox platform provides straightforward stereoselective access to a wide variety offunctionalized 1,2-, 1,3-, 1,4-substituted, and polysubstituted cycloalkyl derivatives from the cheap and readily available carboxylic acidfeedstock.

来源：新浪财经