转自：康龙化成

Stereoselective Amino Alcohol Synthesis via Chemoselective Electrocatalytic Radical Cross-couplings

JiaweiSun1,3, Shuanghu Wang1,3, Kaid C. Harper2, Yu Kawamata1* & PhilS. Baran1*

1 Departmentof Chemistry, Scripps Research, La Jolla, CA, USA. 

2 AbbVie Process Research and Development,North Chicago, IL, USA.

3 These authors contributed equally: JiaweiSun, Shuanghu Wang.

—Nat. Chem. 2025, 10.1038/s41557-024-01695-7

Recommended by Rui Jin _ MC5 

KEYWORDS: electrochemistry (反应类型), flow chemistry (反应类型), decarboxylation (反应类型), radical cross-coupling (反应类型), C(sp2)-C(sp3) (成键类型), C(sp3)-C(sp3) (成键类型), Ni catalysis, bpy, AgNO3 (催化剂), serine-derived cassette (10-RAE) (原料), aryl iodides, aryl bromides, alkenyl bromides, aryloyl chlorides, redox-active esters, benzyl bromides (原料), amino alcohols (产物), stereoselective (其他)

ABSTRACT: Phil S. Baran et al. show a streamlined approach using a serine-derived chiral carboxylic acid in stereoselective electrocatalytic decarboxylative transformations, enabling efficient access to enantiopure amino alcohols. Unlike conventional strategies, this radical method is both modular and general, offering stereoselective and chemoselective synthesis of diverse substituted amino alcohols. For example, aryl, alkenyl, alkyl and acyl fragments can be coupled efficiently with the serine-derived chiral acid under electrocatalytic decarboxylative conditions. This electrocatalytic method is robust and scalable, as demonstrated in a 72-gram-scale flow reaction.

Background and this work:importance of vicinal amino alcohols and synthetic approaches

Development of the reaction platform:10-RAE as a versatile amino alcohol donor for radical coupling. (a) practicalsynthesis of 10-RAE, (b) five reaction modes.

Scope, trendand limitations: Csp3–Csp2 bondformation (selected examples)

Substrate scope: Csp3–Csp3 bondformation

Synthetic application:  facile access to useful amino alcohols

Reaction scale-up employing a flowreactor equipped with a sacrificial electrode

Asimple, serine-derivedcassette (10-RAE) wasdeveloped and tested across an array of useful C–C bond-forming radicalcross-coupling reactions (both electrochemical and chemical) with broad scope (60 examples) as aconsequence ofthe enhanced chemoselectivity ofsuch transforms. Its unassailable utility was demonstrated through thesimplified synthesis of 15 different building blocks and natural products thathave been made before using conventional polar bond analysis. Finally, thescalability of electrocatalytic decarboxylative arylation of such systems wasfield tested, thereby verifying that such chemistry is suitable for both small-and large-scale applications.

Scripps研究所PhilS. Baran课题组开发了一类手性丝氨酸衍生物（10-RAE）脱羧自由基交叉偶联反应（包括电化学法和化学法）构筑C-C键，可以高效获得手性氨基醇。该反应底物范围广（60个例子），并且在传统路线基础上简化合成了15种天然产物。另外，此类反应可以结合流体化学计算进行72g级别的放大反应，预计该反应将在学术和工业中发挥重要作用。

（转自：康龙化成）