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A General Strategy for Copper-Catalyzed Carboamination of Alkynes with Hydrocarbons
Jing Ren1, Shulei Pan1, Ning Wang1
1Institute of Biopharmaceuticals, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu 610041, China.
Abstract:
Herein, we report a novel and efficient copper-catalyzed three-component radical 1,2-carboamination of alkynes, in which picolinamides are used as the nitrogen sources and hydrocarbons bearing diverse C(sp3)-H bonds are employed as the alkylating agents. This process provides a straightforward and cost-effective method for accessing valuable enamide molecules directly from abundant chemical feedstocks, including arylmethanes, alkanes, ethers, and amines. The protocol demonstrates a wide range of substrate compatibility and functional group tolerance, enabling efficient late-stage modifications of complex molecules. Furthermore, this strategy successfully achieves carboamination involving C-H functionalization of polyolefins.
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Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
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Analogous to alkenes, alkynes also undergo acid-catalyzed hydration. While the addition of water to an alkene gives an alcohol, hydration of alkynes produces different products such as aldehydes and ketones.
Preparation of Alkynes: Alkylation Reaction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
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Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.