Copper-mediated regioselective hydrodifluoroalkylation of alkynes

Abstract

A highly regioselective copper-mediated hydrodifluoroalkylation of alkynes with ethyl bromodifluoroacetate or bromodifluoroacetamides has been developed. This strategy provides straightforward access to a variety of difluoroalkylated alkenes under mild reaction conditions with low-cost cuprous bromide and metabisulfite as reduction agents. A wide range of alkynes are applicable under these reaction conditions. The excellent functional-group compatibility and good regio- and stereoselectivities are the notable features of this transformation.

Photocatalytic 1,1-Hydrofluoroalkylation of Alkynes with a Concurrent Vicinal Acylation: An Access to Fluoroalkylated Cyclic Ketones

“…As a consequence, many efforts have been devoted to the introduction of fluoroalkyl groups into organic compounds . In this regard, the radical hydrofluoroalkylation of alkynes − represents a highly efficient method for the direct synthesis of fluoroalkylated compounds (Scheme a). Specifically, Na 2 S 2 O 4 -, AIBN-, Ni-, Cu-, and photoredox-catalyzed or mediated versions have been developed for the access to fluoroalkylated alkenes, with dimethylsulfoxide (DMSO), n -Bu 3 SnH, H 2 O, dimethylformamide (DMF), or amines as the hydrogen atom donor, respectively.…”

“…In this regard, the radical hydrofluoroalkylation of alkynes − represents a highly efficient method for the direct synthesis of fluoroalkylated compounds (Scheme a). Specifically, Na 2 S 2 O 4 -, AIBN-, Ni-, Cu-, and photoredox-catalyzed or mediated versions have been developed for the access to fluoroalkylated alkenes, with dimethylsulfoxide (DMSO), n -Bu 3 SnH, H 2 O, dimethylformamide (DMF), or amines as the hydrogen atom donor, respectively. Note that these methods involve the 1,2-hydrofluoroalkylation of alkynes, while the 1,1-hydrofluoroalkylation of alkynes has not been achieved yet.…”

Copper‐Catalyzed Difluoroalkylation‐Thiolation of Alkenes Promoted by Na2S2O5

“…Moreover, the product 3 aa could be obtained in 37 % yield in the absence of Na 2 S 2 O 5 , which means Na 2 S 2 O 5 might be accelerating the reduction of Cu(II) species. [15a] Based on the above experimental results and previous literature reports, [15] possible reaction mechanism for the difluoroalkylation-thiolation of alkenes is depicted in Scheme 4. Firstly, the initiation of the catalytic cycle occurs with oxidation of Cu(I) species by BrCF 2 CO 2 Et via a single-electron transfer process, generating reactive difluoroalkyl radical I and Cu(II) concomitantly.…”

Promising reagents for difluoroalkylation

“…The group of Wang and Zhao found that the hydrodifluoroalkylation of alkynes with ethyl bromodifluoroacetate could proceeded smoothly mediated by copper. 147 Metabisulfite as reduction agent should be used for this reaction to suppress the homocoupling of terminal alkynes. It can be seen from Scheme 67 that CF 2 COOEt radical was generated from the reaction of BrCF 2 COOEt and Cu(I) via SET process.…”