Joy and Challenges of Alkynylation of Arenes and Heteroarenes through Double C−H Functionalizations

Abstract

A significant number of reactions have appeared in the literature regarding direct oxidative cross‐coupling of arenes and heteroarenes with terminal alkynes achieved through functionalization of C(SP2)−H and C(SP)−H bonds to provide the corresponding alkynylated products. The delights and difficulties of the direct alkynylation have been discussed thoroughly to enlighten this growing area. More emphasis is given to the successful implementation and improvement of various protocols for this transformation. Wherever necessary, the uniqueness of the methods has been shown by highlighting the substrate scope, selectivity, yields along with mechanistic consideration.

Sonogashira coupling of arenediazonium salts: discovery and developments

“…Although the cross-dehydrogenative coupling (CDC), [70][71][72] cross-coupling hydrogen evolution reaction(CCHER), [73][74][75][76] and electrochemical oxidative cross-coupling [77][78][79][80][81] reactions are growing strategies for © AUTHOR(S) direct C-H alkynylation, application of diazonium salts for Sonogashira coupling provides a good alternative for the easy and user-friendly synthesis of diarylacetylenes.…”

Ligand-free Pd/Ag-mediated dehydrogenative alkynylation of imidazole derivatives

“…The development of synthetic protocols that enable the direct and selective functionalization of C sp 2-H bonds are of primary importance in the decoration of the imidazole scaffold. [1][2][3][4][5][6][7][8][9][10] The presence of two nitrogen atoms in the pentatomic structure of this important azole in fact introduces a differentiation in the chemical behaviour of the three C-H bonds, allowing their selective involvement in carbon-carbon bond-forming reactions as long as appropriate experimental conditions are identied.…”

“…During our studies dedicated to the synthesis and investigation of azole-based uorophores featuring a p-conjugated backbone end-capped with electron-donating (EDG) and electron-acceptor (EWG) groups (the so-called "push-pull" systems), [11][12][13][14][15] taking into account the structural characteristics and synthetic versatility of a triple carbon-carbon bond [16][17][18][19][20][21][22][23] that make it an excellent p-spacer, we recently decided to evaluate the possibility of obtaining alkynyl-substituted imidazoles by transition metal-catalyzed C sp 2-C sp bond-forming reactions. Among the synthetic procedures that allow the selective alkynylation of imidazoles and other ve-membered heteroarenes, 5,24 there is no doubt that the possibility of forming the new s carbon-carbon bond through the double activation of two distinct carbon-hydrogen bonds through a crossdehydrogenative alkynylation (CDA) represents the best synthetic approach in terms of atom economy and functional group tolerance (eqn (1), Scheme 1). [25][26][27][28][29][30][31][32][33][34] In fact, when compared with the transition metal-catalyzed direct C sp 2 -H alkynylation protocols involving 1-haloalkynes (the so-called "inverse Sonogashira coupling") (eqn (2), Scheme 1), [35][36][37][38][39][40][41][42][43][44][45] hypervalent iodine reagents (eqn (3), Scheme 1), [46][47]…”

“…[25][26][27][28][29][30][31][32][33][34] In fact, when compared with the transition metal-catalyzed direct C sp 2 -H alkynylation protocols involving 1-haloalkynes (the so-called "inverse Sonogashira coupling") (eqn (2), Scheme 1), [35][36][37][38][39][40][41][42][43][44][45] hypervalent iodine reagents (eqn (3), Scheme 1), [46][47][48] or a,b-ynoic acids (decarboxylative direct arylation) (eqn (4), Scheme 1), 26,49,50 the CDA methodology makes it possible to use terminal alkynes without the need for preliminary activation. 5,24 Despite several papers having been dedicated to the dehydrogenative alkynylation of pyrroles, 27 indoles, 27,31 oxazoles, 27,30,[32][33][34] benzoxazoles, 26,29,30,32,34 thiazoles, 27,30 benzothiazoles, 26,29,31,32,34 pyrazoles,…”

“… 25–34 In fact, when compared with the transition metal-catalyzed direct C sp 2 –H alkynylation protocols involving 1-haloalkynes (the so-called “inverse Sonogashira coupling”) (eqn (2), Scheme 1 ), 35–45 hypervalent iodine reagents (eqn (3), Scheme 1 ), 46–48 or α,β-ynoic acids (decarboxylative direct arylation) (eqn (4), Scheme 1 ), 26,49,50 the CDA methodology makes it possible to use terminal alkynes without the need for preliminary activation. 5,24 …”