Ligand and solvent-free iron catalyzed oxidative alkynylation of azoles with terminal alkynes

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

“…Although mostly ruthenium, rhodium, and palladium‐based catalysts were used for theactivation of C−H bondsto constructC−C andC−heteroatom bonds, a few methods have been depicted using iron as a catalyst whichisspecifically attractive becauseofits low cost and low toxicity. Bobade and co‐workers demonstrated an amusing and useful FeCl 2 ‐catalyzed oxidative alkynylation of azoles with terminal alkynes under ligand‐free and solvent‐free conditions(Scheme ) . With the use of di‐ t ‐butyl peroxide(DTBP)/air as effective oxidant, various benzoxazoles and benzothiazoles were cross‐coupled with different terminal alkynes to produce the desired alkynyl heteroarenes in good yield.Even though more extensive studies are needed to explain the mechanistic features, a possible pathway of the alkynylation of azole is shown in Scheme .…”

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.…”

“…Through a metal catalytic or organocatalytic approach, this simple method provides access to 2-amino and b-amino five-membered heterocycle derivatives that are frequently found in numerous pharmaceuticals and biochemicals, such as an APE 1 inhibitor, Zyprexa, and a Tubulin polymerization inhibitor ( Figure 1). Other oxidants such as CeA C H T U N G T R E N N U N G (SO 4 ) 2 , K 2 S 2 O 8 , and PhIA C H T U N G T R E N N U N G (OAc) 2 did not perform well (Table 1, entries [6][7][8]. In the presence of CuCl (10 mol %) and selectfluor (2.0 equiv) at 120 8C for 6 h with nitromethane (CH 3 NO 2 ) as the solvent, the desired imidation product 1-(5-aminofuran-2-yl)ethanone 2 a was obtained in 55 % yield ( Table 1, entry 1).…”