Recent Advances in the Functionalization of Terminal and Internal Alkynes

Abstract

Alkynes are one of the most fundamental and diverse functional groups utilized in organic synthesis. Over the past few years, the development of efficient synthetic methodologies for the functionalization of alkynes has been an active area of research. A plethora of alkyne functionalization reactions have been reported in the literature to construct functionalized alkynes and alkene scaffolds, which are important building blocks in many natural products, pharmaceuticals, and key intermediates in various synthetic transformations. In this review, we describe the most recent advances in the functionalization of alkynes with an emphasis on substrate scope, limitations, regioselectivity control and applications of these reactions. This review covers the literature from 2016 to 2021.

Transition Metal‐Catalyzed Dearomative Vinylation of Electron Rich Benzenes, Naphthalenes and Indoles with Alkynes

“…The functionalization reactions of alkynes are always significant research topic in chemical research. [20][21][22][23][24][25] Combining the dearomatization of electron rich aromatic compounds with functionalization transformations of alkynes provides a completely novel avenue for dearomative vinylation of electron rich aromatic compounds.…”

Ligand-Controlled Cobalt-Catalyzed Regiodivergent Alkyne Hydroalkylation

“…Recently, base-metal-catalyzed alkyne hydrofunctionalization has emerged as an alternative method to access functionalized alkenes, encompassing the formal addition of a hydrogen and a functional group to the alkynyl triple bonds. − Alkyne hydroalkylation is always highly versatile and stereocontrolled to produce various isomers of alkenes, including 1,1-disubstituted alkenes, 1,2-disubstituted alkenes, and trisubstituted alkenes . For example, copper hydride ,,, and nickel hydride ,, are regio- and stereoselectively inserted into alkynes to generate corresponding organometallic species via ( E )- anti -Markovnikov and Markovnikov additions, respectively .…”

Thiol-Catalyzed Photodriven Stereoselective Hydrodifluoroacetylative Cyclization of Alkyne

“…Installing a gem -difluoro group into an organic molecule can significantly change its physicochemical properties, and this strategy has been widely utilized in compound design for medical and agrochemical applications. − The α,α-difluoroacetyl group is a highly functionalized moiety that has frequently emerged in medicinal chemistry. − Direct hydrodifluoroacetylation of alkene and alkyne with a readily available difluoro reagent through the addition of difluoroacetyl radical species on the unsaturated C–C bonds under mild conditions is an efficient method for building such a difluoroacetyl compound. In addition to conventional methods using a radical initiator, , visible-light-driven C–Br bond cleavage of 2-bromo-2,2-difluoroacetyl compounds is an effective way to furnish the reactive radical species for achieving hydrodifluoroacetylation. − After the emergence of photoreductive hydrodifluoroacetylation with an α-bromodifluoroacetyl compound via direct addition of difluoroacetyl radical species followed by hydrogen atom abstraction, − the more challenging regio- and stereoselective hydrodifluoroacetylation of alkyne has received intensive attention. − Nevertheless, most of the progress was concentrated on the hydrodifluoroacetylation of the terminal aryl alkyne (Figure a). − In these cases, the final products were formed by abstracting a hydrogen atom from the reductant to a vinyl-type radical. Until recently, the photoreductive intramolecular hydrodifluoroacetylation of internal alkyne was achieved by using tertiary diamine as the hydrogen donor (Figure b) .…”