TY - JOUR
T1 - Heteroaryl-Heteroaryl, Suzuki-Miyaura, Anhydrous Cross-Coupling Reactions Enabled by Trimethyl Borate
AU - Kassel, Vincent M.
AU - Hanneman, Christopher M.
AU - Delaney, Connor P.
AU - Denmark, Scott E.
N1 - Funding Information:
We are grateful to the National Institutes of Health (Grant GM R35 127010) for generous financial support. We also thank the UIUC SCS support facilities (microanalysis, mass spectrometry, and NMR spectroscopy) for their assistance. Dr. Gerald Larson (Gelest) is thanked for a generous gift of TMSOK used for this study.
Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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).
AB - 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).
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U2 - 10.1021/jacs.1c06419
DO - 10.1021/jacs.1c06419
M3 - Article
C2 - 34415757
AN - SCOPUS:85114603992
SN - 0002-7863
VL - 143
SP - 13845
EP - 13853
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 34
ER -