摘要：Department of Chemistry, Universityof Missouri, Columbia, Missouri 65211, United States
转自：康龙化成
AshPhos Ligand: Facilitating Challenging Aminations in Five- and Six-MemberedHeteroaryl Halides Using Cyclic Secondary and Bulky Amines
Ashish Dusunge,David K. Leahy,* and Sachin Handa*
Biohaven Pharmaceuticals, New Haven, Connecticut 06510, United States
Department of Chemistry, Universityof Missouri, Columbia, Missouri 65211, United States
—J.Am. Chem. Chem. Au, 2024, doi.org/10.1021/jacsau.4c00772.
KEYWORDS:Buchwald−Hartwigamination(反应类型), C-Ncoupling(反应类型), Pdcatalysis(反应类型),C(sp2)-N(成键类型), cyclic amine(原料), five- and six-membered heteroarylhalides(原料), AshPhos Pdspecies(催化剂), heteroarylamine(产物)
ABSTRACT: D. K.Leahy and S. Handa et al newly developed AshPhos ligand representsa significant advancement in Buchwald−Hartwig aminations, overcoming manylimitations of existing ligands. Created from affordable and accessiblematerials, AshPhos enhances catalytic performance, especially for extremely difficult substrates,by emphasizing the principles of ligand chelation and cooperativity. Itssuccessful synthesis and application in catalytic aminations underscore itspotential for use in the sustainable synthesis of compounds important tomedicinal chemistry, materials, and energy. Further studies validated AshPhos’s effectiveness in coupling challenging heteroaryl bromides and chlorides withvarious amines, including hindered amines and those with multiple heteroatoms.Slightly elevated temperatures were essential to avoid forming inactivespecies, ensuring consistent catalytic turnover.
Background and This Work
Synthesis of AshPhos
Selected Substrate Scope
Role of Ligand in Catalysis
D. K.Leahy and S. Handa et al reported the development of the AshPhos ligand represents a significant advancement in the field of Buchwald−Hartwigamination. Derived from cost-effective and readily available startingmaterials, AshPhos addresses the limitations of existing ligands by offering enhanced catalyticperformance, particularly for challenging substrates. The successful synthesisand characterization of AshPhos,along with its demonstrated efficacy in catalytic amination reactions,highlight its potential for scalable and sustainable applications in syntheticchemistry. AshPhos hasproven highly effective for coupling challenging heteroaryl bromides andchlorides with various amines, including those containing multiple heteroatoms.
来源：新浪财经
