Massachusetts Institute of Technology

Gero Nordmann

Stephen L Buchwald

Artis Klapars

Gabriel E Job

Jon Clarence Antilla

Fuk Y Kwong

Edward J Hennessy

Martina Wolter

Martina Uhlenbrock

The present invention relates to copper-catalyzed carbon-heteroatom and carbon-carbon bond-forming methods, such as the reaction of Z-X with C(L)(R)(R')in the present of a catalyst and a base, thereby forming C(Z)(R)(R&#x2032;); wherein X represents I, Cl, alkylsulfonate, or arylsulfonate; Z represents optionally substituted aryl, heteroaryl or alkenyl; L represents H or a negative charge; catalyst comprises a copper atom or ion, and a ligand, wherein the ligand is an optionally substituted aryl alcohol, alkyl amine, 1,2-diamine, 1,2-aminoalcohol, 1,2-diol, imidazolium carbene, pyridine, or 1,10-phenanthroline; the ligand is a chelating ligand; and the base represents a Bronsted base; R represents H, optionally substituted alkyl, cycloalkyl, aralkyl, aryl, or heteroaryl; R&#x2032; represents independently for each occurrence H, alkyl, cycloalkyl, aralkyl, aryl, or heteroaryl, formyl, acyl, &#x2014;COR&#x2033;, &#x2014;C(O)N(R), sulfonyl, &#x2014;P(O)(OR&#x2033;), &#x2014;CN, or &#x2014;NO; R&#x2033; represents independently for each occurrence optionally substituted alkyl, cycloalkyl, aralkyl, aryl, or heteroaryl; and C(R&#x2032;)(R) taken together may represent nitrile.

Copper-catalyzed formation of carbon-heteroatom and carbon&#x2014;carbon bonds

The present invention relates to copper-catalyzed carbon-heteroatom and carbon-carbon bond-forming methods. In certain embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between the nitrogen atom of an amide or amine moiety and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In additional embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between a nitrogen atom of an acyl hydrazine and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In other embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between the nitrogen atom of a nitrogen-containing heteroaromatic, e.g., indole, pyrazole, and indazole, and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In certain embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-oxygen bond between the oxygen atom of an alcohol and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. The present invention also relates to copper-catalyzed methods of forming a carbon-carbon bond between a reactant comprising a nucleophilic carbon atom, e.g., an enolate or malonate anion, and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. Importantly, all the methods of the present invention are relatively inexpensive to practice due to the low cost of the copper comprised by the catalysts.

Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds

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Gero Nordmann