Open AccessHeteroaryl–Heteroaryl, Suzuki–Miyaura, Anhydrous Cross-Coupling Reactions Enabled by Trimethyl Borate
Author(s) -
Vincent M. Kassel,
Christopher M. Hanneman,
Connor P. Delaney,
Scott E. Denmark
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.1c06419
Subject(s) - chemistry , anhydrous , nucleophile , base (topology) , coupling reaction , electrophile , medicinal chemistry , catalysis , boron , suzuki reaction , combinatorial chemistry , organic chemistry , palladium , mathematics , mathematical analysis
Reaction conditions have been developed for refractory heteroaryl-heteroaryl Suzuki-Miyaura cross-couplings. The reported method employs neopentyl heteroarylboronic esters as nucleophiles, heteroaryl bromides and chlorides as the electrophiles, and the soluble base potassium trimethylsilanolate (TMSOK) under anhydrous conditions. The addition of trimethyl borate enhances reaction rates by several mechanisms, including (1) solubilization of in situ -generated boronate complexes, (2) preventing catalyst poisoning by the heteroatomic units, and (3) buffering the inhibitory effect of excess TMSOK. The use of this method enables cross-coupling of diverse reaction partners including a broad range of π-rich and π-deficient heteroaryl boronic esters and heteroaryl bromides. Reactions proceed in good yields and short reaction times (3 h or less).