Nickel-Catalyzed Cyanation of Unactivated Alkyl Sulfonates with Zn(CN).

Cyanation of unactivated primary and secondary alkyl mesylates with Zn(CN) catalyzed by nickel has been developed. The reaction provides an efficient route for the synthesis of alkyl nitriles with wide substrate scope, good functional group tolerance, and compatibility with heterocyclic compounds. Mechanistic studies indicate that alkyl iodide generated in situ serves as the reactive intermediate and the gradual release of alkyl iodide is crucial for the success of the reaction.

Dehalogenative Deuteration of Unactivated Alkyl Halides Using DO as the Deuterium Source.

The general dehalogenation of alkyl halides with zinc using DO or HO as a deuterium or hydrogen donor has been developed. The method provides an efficient and economic protocol for deuterium-labeled derivatives with a wide substrate scope under mild reaction conditions. Mechanistic studies indicated that a radical process is involved for the formation of organozinc intermediates.

Nickel-Catalyzed Cyanation of Unactivated Alkyl Chlorides or Bromides with Zn(CN).

A nickel-catalyzed cyanation of unactivated secondary alkyl chlorides or bromides using less toxic Zn(CN) as the cyanide source has been developed. The reaction features the use of air-stable and inexpensive NiCl·6HO or Ni(acac) as the precatalysts and offers an efficient synthesis of a broad range of alkyl nitriles. Cyanation of primary alkyl chlorides or bromides was also achieved by reaction with Zn(CN) in the presence of n-BuNCl without the need of nickel catalyst.

General and Mild Nickel-Catalyzed Cyanation of Aryl/Heteroaryl Chlorides with Zn(CN): Key Roles of DMAP.

A new and general nickel-catalyzed cyanation of hetero(aryl) chlorides using less toxic Zn(CN) as the cyanide source has been developed. The reaction relies on the use of inexpensive NiCl·6HO/dppf/Zn as the catalytic system and DMAP as the additive, allowing the cyanation to occur under mild reaction conditions (50-80 °C) with wide functional group tolerance. DMAP was found to be crucial for successful transformation, and the reaction likely proceeds via a Ni(0)/Ni(II) catalysis based on mechanistic studies.