Studies in novel transition-metal-catalyzed oxidative coupling reactions

Jinmin Miao, Purdue University

Abstract

Transition-metal-catalyzed oxidative coupling reactions are important tools for the construction of carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds from simple starting materials. A series of novel and synthetically useful reactions have been developed and are herein described. Palladium-catalyzed chemoselective decarboxylative cross-coupling of benzoic acids with α-oxocarboxylic acids was realized via an arene sp 2 C-H functionalization process. This work represents the first example of transition-metal-catalyzed cross-coupling reactions with two acids acting in different roles. The synthetic utility of this method was confirmed by the synthesis of pitofenone, an antispasmodic used in the combined drug Spasmalgon. A highly site-selective and diastereoselective fluorination of aliphatic amides via a palladium-catalyzed bidentate ligand-directed C-H bond functionalization process on unactivated sp3 carbons was developed. A wide variety of β-fluorinated amino acid derivatives and aliphatic amides, important motifs in medicinal and agricultural chemistry, were prepared with palladium acetate as the catalyst and selectfluor as the fluorine source. The synthesis for cinnolines from N-phenylhydrazones was performed through an oxidation/cyclization sequence, representing the first copper-catalyzed coupling reaction of hydrazones through a C(sp 3)-H bond functionalization process. The method provides an environmentally friendly and atom-efficient approach to biologically active cinnoline derivatives. A novel rhodium-catalyzed imination of sulfoxides using O-(2,4-dinitrophenyl)-hydroxylamine was developed under mild conditions with good functional group tolerance. The reaction provides an efficient access to free NH-sulfoximines, an important structural unit in a variety of biologically active compounds.

Degree

Ph.D.

Advisors

Ge, Purdue University.

Subject Area

Molecular chemistry|Chemistry

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