Copper(II)‐Promoted, One‐Pot Conversion of 1‐Alkynes with Anhydrides or Primary Amines to the Respective 2,5‐Disubstituted Furans or Pyrroles under Microwave Irradiation Conditions

Abstract

Furans and pyrroles are preparedf rom 1-alkynes by using aC u(II)-promoted, one-pot, microwave irradiationm ethod.G laser coupling of 1-alkynes and cyclization of the resulting 1,3-diyne in the presence of an anhydride or ap rimary amine results in the formation of the respective 2,5-diarylor 2,5-dialkyl-substituted furans andpyrroles.Keywords: copper;c yclization;h eterocycles;m icrowave heating Five-memberedh eterocyclic compoundsh ave attracted much attention over manyy ears because of their importance as building blocks for pharmaceuticals, molecular sensors ands emiconductors.[1] Numerous transitionm etal-catalyzed methodsh aveb eend evised for the preparation of these substances.[2] However, transitionm etal-promoted processesp reviously developed for this purpose have some drawbacks associated with the use of 1,3-diyne as as tarting material [3] and expensive transitionm etals,s uch as Au, [4] Ru [5] and Rh, [6] as catalysts.I na ddition,m ost of the protocols generate 2,5-diaryl-substituted five-membered heterocycles. [7] In this investigation described below, we have developed an ovel, one-pot,m icrowave irradiation-promoted, Cu(II)-catalyzed method for the synthesiso f 2,5-disubstituted furans and pyrroles from 1-alkynes and the respective anhydrides and primary amines as heteroatom source.T he reactions proceedt hrough ap athwayi nvolving intermolecular homocoupling of the 1-alkyne ands ubsequent cyclization of the resulting 1,3-diyne with the heteroatom precursors.C ompared with previouslyr eported methods, which have focused on 2,5-diaryl-substitued targets, the new synthetic protocol is unique in that it can be utilized to produce alkyl-as well as aryl-substituted furans and pyrrolesi nahighly concise and efficient manner. To the best of our knowledge,t here has been no report on the one-pot direct synthesis of aliphatic disubstituted heterocyclic compoundsfrom 1-alkylalkynes.In as tudy aimed at optimizing the conditions for the newly developed process,1 -octyne (1a)w as chosen as the prototypical 1-alkyne substrate.T he results (Table 1) show that reactiono f1a with acetic anhydride (Ac 2 O, 2)a nd ammonium acetate (NH 4 OAc, 3)c arried out in the presenceo fC u(OAc) 2 ·H 2 O( 4, 1equiv.)a t1 50 8 8Cf or 10 min under microwave irradiation conditions generates 2,5-dihexylfuran (5a)i n a9 5% GC yield (entry 1). Ac 2 O( 2)a nd NH 4 OAc( 3) are important reagents for this process because reactions catalyzed by Cu(OAc) 2 ·H 2 O( 4,1equiv.) in the absence of either of these respective substances generate 5a in only 44% and 24% yields (entries2and 3) and when botho ft hese reagents are not useda4% yield of 5a is obtained (entry 4). Ther eactiono f1 -octyne (1a)u tilizingb enzoic anhydride (Bz 2 O) with NH 4 OAc( 3)g ives 5a in 19% yield (entry 5). In the case of using NH 4 Cl instead of NH 4 OAc( 3), the reaction of 1a with Ac 2 O( 2)g eneratesatrace amount of 5a (entry 6). Use of CuCl 2 or CuI instead of Cu(OAc) 2 ·H 2 O( 4)d oes not produce any observable amount of 5a (entries 7a nd 8). Intere...

Catalytic Hydrofunctionalization Reactions of 1,3-Diynes

“…In all the cases, the central pyrrolic unit was generated through the initial copper-catalyzed annulation of a primary amine with a 1,3-diynic system. In this context, we must note that several 1,2,5-trisubstituted pyrroles were synthesized by Jun and colleagues by reacting terminal alkynes with primary amines in the presence of Cu(OAc) 2 •H 2 O (Scheme 34) [90]. The process was performed under microwave (MW) irradiation and involved the initial Cu(OAc) 2 -promoted Glaser homocoupling of the alkynes, followed by the double hydroamination of the resulting diynes.…”

Benefits and applications of microwave-assisted synthesis of nitrogen containing heterocycles in medicinal chemistry

“…succeeded in the synthesis of pyrroles bearing increased sites of substitution compared to previous examples through a Cu(II)-promoted, one-pot, MW irradiation reaction of 1-alkynes 7 and primary amines 8 to yield N-2,5-trisubstituted pyrroles 9 (eqn (3)). 20 The promotion of the following reaction under MW conditions can be directly attributed to the heterogeneous composition of the reaction system. The reaction is comprised of a highly polar and thus strongly MW-absorbing solvent, methanol, and a ferromagnetic metal catalyst, Cu, that can also strongly interact with the electromagnetic eld.…”

Metal-Catalyzed Synthesis and Transformations of β-Haloenol Esters

“…In this regard, a large number of (Z)-and (E)-β-haloenol esters (both chlorides, bromides and iodides) have been successfully coupled with alipahic and aromatic alkynes, 1,3-enynes or propargylic alcohols to generate the corresponding enynyl ester products in high yields and with complete preservation of the C=C bond stereochemistry of the starting olefins (the results obtained in references [60,76,77] are depicted in Scheme 19). The main interest in these Sonogashira-type reactions is that the enynyl ester products can be employed as starting materials for the generation of polysubstituted furans via metal-catalyzed [76,77] or halogen-induced electrophilic cyclization reactions [30,[79][80][81]. Illustrative examples are shown in Scheme 20.…”

“…Illustrative examples are shown in Scheme 20. The main interest in these Sonogashira-type reactions is that the enynyl ester products can be employed as starting materials for the generation of polysubstituted furans via metal-catalyzed [76,77] or halogen-induced electrophilic cyclization reactions [30,[79][80][81]. Illustrative examples are shown in Scheme 20.…”