New aryl/heteroaryl C-N bond cross-coupling reactions via arylboronic acid/cupric acetate arylation
Patrick Y. S. Lam*, Charles G. Clark, Simon Saubern, Jessica Adams, Michael P. Winters, Dominic M. T. Chan and Andrew Combs
*Bristol-Myers Squibb, P.O. Box 5400, Princeton, New Jersey 08543-5400, Email:
patrick.lambms.com
P. Y. S. Lam, C. G. Clark, S. Saubern, J. Adams, M. P. Winters, D. M. T. Chan, A. Combs, Tetrahedron Lett., 1998, 39, 2941-2944.
DOI: 10.1016/S0040-4039(98)00504-8
Abstract
A mild, new aryl/heteroaryl C-N bond cross-coupling reaction via the arylboronic acid/cupric acetate arylation of N-H containing heteroarenes proceeds at room temperature exposed to air, and works for many heteroarenes and arylboronic acids providing good yields of N-arylated heteroarenes.
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Details
The document discusses a new aryl/heteroaryl C-N bond cross-coupling reaction using arylboronic acid and cupric acetate for the arylation of N-H containing heteroarenes. This methodology is mild, operates at room temperature, and is exposed to air, providing good yields for various heteroarenes and arylboronic acids. Traditional methods like the Ullmann reaction require high temperatures and give variable yields, while newer methods using aryl halides with palladium or nickel catalysts have limitations. The new reaction involves adding arylboronic acid, base (pyridine), heteroarene, anhydrous cupric acetate, and molecular sieves in methylene chloride, stirred at room temperature for 2 days. The reaction tolerates different electronic natures of arylboronic acids and works well for nucleophilic heterocycles like pyrazole, imidazole, indazole, and benzimidazole, but yields are lower for less nucleophilic heterocycles. The reaction mechanism likely involves cupric acetate forming a complex with the heterocycle, transmetallating with arylboronic acid, and undergoing reductive elimination. This methodology is ideal for generating heterocycle-containing libraries and is being optimized further. The document also includes a representative procedure and references for further reading.
New N- and O-arylations with phenylboronic acids and cupric acetate
D. M. T. Chan, K. L. Monaco, R.-P. Wang, M. P. Winteres, Tetrahedron Lett., 1998, 39, 2933-2936.
Key Words
Chan-Lam Coupling, N-Arylation
ID: J72-Y1998-440