Catalyst‐Dependent Divergent Synthesis of Pyrroles from 3‐Alkynyl Imine Derivatives: A Noncarbonylative and Carbonylative Approach

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...

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

Lee

Jun

2015

Regioselective Synthesis of Pyrroles from Alkyne‐Isocyanide Click Reactions: An Angle Strain‐Induced Bond Migration Approach

George

Kim

2016

Thed irect regioselective synthesis of highly functionalized pyrrolesw ith twod ifferent electron-withdrawing groups has been developed using an angle strain-induced 1,2-shift of an electron-withdrawing group in 2H-pyrroles.T he preferential migration aptitude of an electron-withdrawing group over alkyla nd aryl groups is believed to be the result of the orbital overlap between the internal alkene and the electron-withdrawing group. Then ewly developed regioselective synthesis of pyrroles featuresawide substrate scope,s imple reaction set-up, andh igh yields( 60-82%), capturing the essence of alkyne-isocyanide "click" reactions.Scheme1.Alkyne-isocyanide "click" reactions and angle strain-induced bond migration to substituted pyrroles.

The Construction of Nitrogen‐Containing Heterocycles from Alkynyl Imines

Shan

Zhao

et al. 2020

Nitrogen‐containing heterocycles have attracted considerable attention due to their extensive applications in the fields of organic synthesis, pharmaceuticals, agrochemicals, and materials science. This review focuses on the recent advances in the synthesis of nitrogen‐containing heterocycles via the cyclization of alkynyl imines. By using this protocol, a variety of nitrogen‐containing heterocycles, mainly including four‐, five‐, six‐, and seven‐membered nitrogen‐containing heterocycles, aza‐spirocycles, and fused aza‐heterocycles, could be obtained efficiently under mild conditions. Additionally, mechanistic features of these transformations are also discussed.