Rapid access to pyrazolo[3,4-c]pyridines via alkyne annulation: limitations of steric control in nickel-catalyzed alkyne insertions.
Polyfunctionalized pyrazolo[3,4-c]pyridines were readily prepared by the annulation of alkynes with tert-butyl 4-iodopyrazolocarboximines. The reaction was found to be catalyzed by both NiBr2(PPh3)2/Zn or PdCl2(PhCN)2 to yield complex heterocycles in good to moderate yields. Annulation using nickel catalysis was found to be regio-random, implying that steric control in nickel-catalyzed alkyne insertion has limitations based on the character of the Ni-C bond in the pre-insertion complex.
Heller
Stephen T
ST
Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. sheller@berkeley.edu
Natarajan
Swaminathan R
SR
D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism
D000480:Alkynes; D011720:Pyrazoles; D011725:Pyridines; D010165:Palladium; D009532:Nickel