转自：康龙化成
Enhancing the Sustainability andScalability of Transition-Metal-Free Stereoretentive Decarboxylative Amidation with Dioxazolones
Jeonguk Kweon,§ Minjeong Lee,§ Dongwook Kim,and Sukbok Chang*
Departmentof Chemistry, Korea Advanced Institute of Science and Technology (KAIST),Daejeon 34141, South Korea
—Org.Process Res. Dev., 2024, DOI: 10.1021/acs.oprd.4c00247
Recommended by Chaoyou Liu _ PDM
Keywords: Decarboxylation(反应类型), amidation (反应类型),C(sp3)-N (成键类型),1,4,2-dioxazol-5-ones (试剂),chiral acid (原料),chiral amine (产物)
ABSTRACT: Authorspresent an investigation into the scalability and sustainability ofdecarboxylative amidation forconstructing C(sp3)−N bonds using dioxazolones asthe amino source under transition-metal-free and ambient conditions. One of theconcerns regarding the sustainability of the previously developed amidation protocol, mainly arising from the use of dimethyl sulfoxide (DMSO), wassuccessfully addressed through reoptimization. Ethylacetate cannow serve as an effective, environmentally friendly alternative reactionmedium. Authors also present the results of a sensitivity study of the newlyoptimized amidation conditions, examining parameters such as O2 levels, concentrations, water content, and temperatures. The practicability ofthis stereoretentive decarboxylative amidation hasbeen validated through multigram-scale reactions (5−50 mmol), includingoptically active carboxylic acids such as (S)-Naproxen
Background
Reaction Conditions Optimization
ReactionSensitivity Test of Decarboxylative Amidationfor (S)-Naproxen
Gram-Scale Reaction
Decagram-ScaleReaction of (S)-Naproxen
（转自：康龙化成）