Highly Chemoselective, Transition-Metal-Free Transamidation of Unactivated Amides and Direct Amidation of Alkyl Esters by N-C/O-C Cleavage
Guangchen Li, Chong-Lei Ji, Xin Hong*, Michal Szostak*
*Department of Chemistry, Zhejiang University, Hangzhou 310027, China; Department of Chemistry, Rutgers University, Newark, New Jersey 07102, United States,
Email: hxchem
zju.edu.cn, michal.szostakrutgers.edu
G. Li, C.-L. Ji, X. Hong, M. Szostak, J. Am. Chem. Soc., 2019, 141, 11161-11172.
DOI: 10.1021/jacs.9b04136
Abstract
A general, mild, and highly chemoselective method for transamidation of unactivated tertiary amides by a direct acyl N-C bond cleavage with non-nucleophilic amines is performed in the absence of transition metals and operates under unusually mild reaction conditions. A direct amidation of abundant alkyl esters affords amide bonds with exquisite selectivity by acyl C-O bond cleavage.
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General Procedure for Transamidation Reactions
An oven-dried vial equipped with a stir bar was charged with an amide substrate (neat, 1.0 equiv), amine (typically, 2.0 equiv) placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles. Toluene (typically, 0.25 M) and LiHMDS (1.0 M in THF, typically, 3.0 equiv) were sequentially added with vigorous stirring at room temperature, and the reaction mixture was stirred at room temperature for an indicated time. After the indicated time, the reaction mixture was quenched with NH4Cl (aq., 1.0 M, 1 mL), diluted with EtOAc (10 mL), the organic layer was washed with water (1 x 10 mL), brine (1 x 10 mL), dried and concentrated. A sample was analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain conversion, yield and selectivity using internal standard and comparison with authentic samples. Purification by chromatography on silica gel (EtOAc/hexanes) afforded the title product.
General Procedure for Amidation Reactions
An oven-dried vial equipped with a stir bar was charged with an ester substrate (neat, 1.0 equiv), amine (typically, 1.2 equiv) placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles. Toluene (typically, 0.25 M) and LiHMDS (1.0 M in THF, typically, 2.0 equiv) were sequentially added with vigorous stirring at room temperature, and the reaction mixture was stirred at room temperature for an indicated time. After the indicated time, the reaction mixture was quenched with NH4Cl (aq., 1.0 M, 1 mL), diluted with EtOAc (10 mL), the organic layer was washed with water (1 x 10 mL), brine (1 x 10 mL), dried and concentrated. A sample was analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain conversion, yield and selectivity using internal standard and comparison with authentic samples. Purification by chromatography on silica gel (EtOAc/hexanes) afforded the title product.
Key Words
ID: J48-Y2019
