Ligand-enabled reactivity and selectivity in a synthetically versatile aryl C-H olefination.
The Mizoroki-Heck reaction, which couples aryl halides with olefins, has been widely used to stitch together the carbogenic cores of numerous complex organic molecules. Given that the position-selective introduction of a halide onto an arene is not always straightforward, direct olefination of aryl carbon-hydrogen (C-H) bonds would obviate the inefficiencies associated with generating halide precursors or their equivalents. However, methods for carrying out such a reaction have suffered from narrow substrate scope and low positional selectivity. We report an operationally simple, atom-economical, carboxylate-directed Pd(II)-catalyzed C-H olefination reaction with phenylacetic acid and 3-phenylpropionic acid substrates, using oxygen at atmospheric pressure as the oxidant. The positional selectivity can be tuned by introducing amino acid derivatives as ligands. We demonstrate the versatility of the method through direct elaboration of commercial drug scaffolds and efficient syntheses of 2-tetralone and naphthoic acid natural product cores.
Wang
Dong-Hui
DH
Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Engle
Keary M
KM
Shi
Bing-Feng
BF
Yu
Jin-Quan
JQ
D000475:Alkenes / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D055598:Chemical Phenomena; D006859:Hydrogen / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D010648:Phenylacetates / Q000737:chemistry; D010666:Phenylpropionates / Q000737:chemistry; D044024:Tetralones / Q000138:chemical synthesis*
D000475:Alkenes; D000596:Amino Acids; D002264:Carboxylic Acids; D008024:Ligands; D009281:Naphthalenes; D016877:Oxidants; D010648:Phenylacetates; D010666:Phenylpropionates; D044024:Tetralones; C085312:1-naphthoic acid; C035253:3-phenylpropionic acid; D010165:Palladium; D002244:Carbon; D006859:Hydrogen; C025136:phenylacetic acid; D010100:Oxygen