Enantioselective Multicomponent Electrochemical Difunctionalization of Terminal Alkynes
Qiannan Wang1, Xinyu Wang1, Yong Liu1
1Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, China.
Abstract:
The direct functionalization of alkyne triple bonds using a radical strategy provides an efficient platform for creating a wide range of substituted alkenes. However, developing a multicomponent enantioselective radical reaction using feedstock alkynes to forge all-carbon quaternary stereocenters─while addressing challenges related to compatibility, selectivity, and efficiency─remains relatively rare. Here we report an enantioselective electrochemical nickel-catalyzed three-component cross-coupling of readily available terminal alkynes, diverse racemic alkyl radical precursors, and group transfer reagents (such as (TMS)3Si-H, RSe-SeR, RTe-TeR, and CHI3), achieving excellent regio-, stereo-, and enantioselectivities (more than 70 examples, up to 95% ee). Electricity-mediated difunctionalizations significantly expand the scope of both aliphatic and aromatic alkynes, demonstrating excellent functional group compatibility. The key to success lies in the rational design of anodically generated nickel-bound tertiary radical intermediates, which stereoselectively capture alkynes to form vinyl radicals and participate in subsequently diverse group transfer processes to enable the intermolecular and anti-stereoselective difunctionalization of alkynes. This approach allows the transformation of terminal alkynes into diverse structural entities with α-quaternary stereogenic centers.
Related Concept Videos
02:27Preparation 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.
02:42Acidity of 1-Alkynes
The acidic strength of hydrocarbons follows the order: Alkynes > Alkenes > Alkanes. The strength of an acid is commonly expressed in units of pKa — the lower the pKa, the stronger the acid. Among the hydrocarbons, terminal alkynes have lower pKa values and are, therefore, more acidic. For example, the pKa values for ethane, ethene, and acetylene are 51, 44, and 25, respectively, as shown here.
02:47Alkynes 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.
02:38Electrophilic Addition to Alkynes: Halogenation
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
02:34Preparation of Alkynes: Dehydrohalogenation
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.
02:24Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
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.