Cyanation of arenes via iridium-catalyzed borylation.
We report a method to conduct one-pot meta cyanation of arenes by iridium-catalyzed C-H borylation and copper-mediated cyanation of the resulting arylboronate esters. This process relies on a method to conduct the cyanation of arylboronic esters, and conditions for this new transformation are reported. Conditions for the copper-mediated cyanation of arylboronic acids are also reported. By the resulting sequence of borylation and cyanation, 1,3-disubstituted and 1,2,3-trisubstituted arenes and heteroarenes containing halide, ketone, ester, amide, and protected alcohol functionalities are converted to the corresponding meta-substituted aryl nitriles. The utility of this methodology is demonstrated through the conversion of a protected 2,6-disubstituted phenol to 4-cyano-2,6-dimethylphenol, which is an intermediate in the synthesis of the pharmaceutical etravirine. The utility of the method is further demonstrated by the conversion of 3-chloro-5-methylbenzonitrile, produced through the one-pot C-H borylation and cyanation sequence, to the corresponding 3,5-disubstituted aldehydes, ketones, amides, carboxylic acids, tetrazoles, and benzylamines.
Liskey
Carl W
CW
Department of Chemistry, University of Illinois, 600 South Matthews Avenue, Urbana, Illinois 61801-3602, USA.
Liao
Xuebin
X
Hartwig
John F
JF
D001897:Boronic Acids / Q000737:chemistry*; D002384:Catalysis; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D007495:Iridium / Q000737:chemistry*; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*
D001897:Boronic Acids; D006841:Hydrocarbons, Aromatic; D009570:Nitriles; D009942:Organometallic Compounds; D007495:Iridium