康 · 学术 | Reaction of the Day No. 1732

DCPDC-Mediated Facile Amide-Bond Formation of Non-Nucleophilic and Hindered Amines

Atanu Patra*, Mohana Rao Vippila*, Mahua Baishnab, Balaji Deva, Manivannan Muthukumar, Arvind Mathur, Rich Tester

Department of Chemical Synthesis, Biocon Bristol-Myers Squibb Research and Development Center, Bengaluru, India;

—Synlett.,2026, 37(09), 1074-1080.

Recommended by Shi Li_MOC and Lili Zhou_MC3

KEYWORDS:Amidation(反应类型), C(sp2)-N,C(sp2)-O, C(sp2)-S (成键类型), carboxylic acids, DCPDC, amines, phenol, thiophenol (原料), amides,Thioester, ester (产物) 

ABSTRACT: A facile synthesis of amide bond formation involving non-nucleophilic and hindered amines is reported. DCPDC found itself to be an economical reagent for amide synthesis by activation of carboxylic acid. The reaction proceeds via diester intermediate formed by reaction between carboxylic acid and DCPDC. The approach presents a broad range of substrate scopes with 39 examples given. Notably, the reaction works equally well on scale up providing the desired product in excellent yield without any purification. More interestingly, their preliminary results indicated retention of configuration for chiral amines and acids.

Background and This Work: Mode of reactions of DCPDC – multifunctional reagent

Optimization of Reaction Conditions

Substrate Scope of Amines

Substrate Scope of Carboxylic Acids

DCPDC-Mediated (Thio)Ester Synthesis

Summary and Comments

In conclusion, Atanu Patra et al. have successfully introduced DCPDC as a unique and operationally simple acid–amine coupling reagent. The use of a simple and economical coupling reagent as a reaction partner enabled obtaining a panel of amides from challenging non-nucleophilic and hindered amines with good to excellent yields. Moreover, chiral amines and acids retain their chirality in the final products with good yields and excellent ee values. This method is likely to offer a variety of amides using a broad spectrum of electronically and sterically hindered amines under one roof. Therefore, this methodology will extend the current toolbox toward late-stage functionalization.