康 · 学术 | Reaction of the Day No. 1735

Enantioconvergent Decarboxylative Arylation of Serine and Isoserine Derivatives with Aryl Halides: Modular Access to Chiral 1,2-Amino Alcohols

Quan Zhu, Wei-Cheng Zhao, Cheng-Yu Wang, Chen-Hui Jiang, Si-Yuan Zhou, Chaodi Dai, Craig S. Day,* Shang-Zheng Sun,* and Xi-Sheng Wang*

Department of Chemistry, University of Copenhagen, 2100 Copenhagen, Denmark;

Department of Chemistry, University of Science and Technology of China, Hefei 230026, China; School of Chemistry and Chemical Engineering, Guizhou University, Guiyang, Guizhou 550025, China

—J. Am. Chem. Soc., 2026, 148 (20), 20348-20355.

Recommended by Shi Li_MOC

KEYWORDS: Decarboxylation, Ni catalysis, arylation, Enantioselective (反应类型), serine- and isoserine-derived redox-active esters (RAEs), aryl halides (原料),  chiral 1,2-amino alcohols (产物), C(sp2)-C(sp3) (成键类型)

ABSTRACT: Enantioenriched 1,2-amino alcohols are key motifs in biologically active compounds and invaluable chiral synthons. Despite significant advances in relevant preparations, there is still a scarcity of modular and enantioconvergent methods for the synthesis of chiral vicinal amino alcohols from readily available precursors. Herein, theauthors describe a Ni-catalyzed enantioconvergent decarboxylative arylation, leveraging racemic serine- and isoserine-derived redox-active esters (RAEs) as coupling partners. These RAEs serve as inexpensive, bench-stable, and readily available alkyl radical precursors. This protocol offers a robust, divergent, and versatile catalytic platform, enabling the construction of enantioenriched α- and β-arylated vicinal amino alcohols. It features high modularity, exceptional functional group tolerance, a broad substrate scope, and precise stereocontrol under mild conditions. Its utility is demonstrated through the successful late-stage functionalization of complex bioactive molecules, offering a streamlined route to a diverse array of novel analogues from a valuable scaffold.

Background and This Work

Optimization

Substrate Scope (Selected) 

Synthetic Applications

Proposed Mechanism

Summary and Comments

Prof. Xi-Sheng Wang et al. have developed an unprecedented Ni-catalyzed enantioconvergent decarboxylative arylation of racemic serine- and isoserine-derived RAE with aryl halides under mild conditions. The alkyl precursor RAE 1 can be readily prepared as a bench-stable solid from inexpensive, naturally abundant, and commercially available serine or isoserine. This protocol is distinguished by its modularity, exceptional functional group tolerance, a wide scope, and excellent stereocontrol, even when applied to challenging substrate combinations. Moreover, the enantioenriched α- and β-arylated vicinal amino alcohols are readily accessible via simple workup of the final product. This approach offers a valuable alternative to existing methodologies for constructing chiral 1,2-amino alcohol scaffolds.