Palladium-Catalyzed Oxidative Alkynylation of Heterocycles with Terminal Alkynes under Air Conditions

Abstract

Pd-Catalyzed oxidative alkynylation of azoles with terminal alkynes was developed via simultaneous activation of both heterocyclic sp(2) C-H and alkynyl sp C-H bonds. The choice of palladium catalyst source and external base resulted in being important factors for performing the reaction with high efficiency and selectivity, and air was successfully utilized as an environmental oxidant in the present alkynylation procedure.

Chemicals from Alkynes with Palladium Catalysts

“…Thus, Nalkylated 3-methylindoles have been alkynylated at C-2 with terminal alkynes in a process catalyzed by K 2 PdCl 4 (10 mol%) using cesium carbonate as base and oxygen (1 bar) and pivalic acid as oxidants, in DMSO as solvent at 80 ºC. 327 Another more simple oxidative 2-alkynylation of oxazoles and thiazoles has been performed using Pd(PPh 3 ) 4 as catalyst (5 mol%) and lithium tert-butoxide as base, using air as oxidant in toluene at 100 ºC, 328 …”

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

“…One elegant palladium‐catalyzed alkynylation of azoles with terminal alkynes was demonstrated by Chang et al., where a wide range of azoles and alkynes were used to get the alkynylated products (Scheme ) . Their optimization studies show that the choice of catalyst and external base is very much crucial since omnipresence of Pd(PPh 3 ) 4 catalyst and LiO t Bu base under aerobic atmosphere provides the best results.…”

Regioselective CH Imidation of Five‐Membered Heterocyclic Compounds through a Metal Catalytic or Organocatalytic Approach

“…Regioselectivity was achieved through a metal catalytic or organocatalytic approach. [6] Over the past decades, a variety of elegant methods have been developed for the intermolecular C À H arylation, [7] alkylation, [8] olefination [9] and alkynylation [10] of azoles. [4] The five-membered heterocycles pyrrole, furan, and thiophene with amine substituents are important synthetic intermediates and employed widely in medicinal chemistry.…”

“…[4] The five-membered heterocycles pyrrole, furan, and thiophene with amine substituents are important synthetic intermediates and employed widely in medicinal chemistry. [6] Over the past decades, a variety of elegant methods have been developed for the intermolecular C À H arylation, [7] alkylation, [8] olefination [9] and alkynylation [10] of azoles. Therefore, direct functionalization of these compounds is economically attractive and of important synthetic usage.…”

“…[5] These skeletons have classically been prepared by cyclocondensation reactions, forming the heterocyclic ring in the key step from two functionalized precursors. [6] Over the past decades, a variety of elegant methods have been developed for the intermolecular C À H arylation, [7] alkylation, [8] olefination [9] and alkynylation [10] of azoles. Transition-metal-catalyzed synthetic transformations have been considered as one of the most reliable and powerful tools for connection of such chemical bonds, giving complex molecular structures in an efficient and economical manner.…”