A Novel Facile Synthesis Method of N‐Vinylpyrroles

A facile and effective synthesis of N‐vinylpyrroles had been explored. The synthetic approach was practicable for preparation of N‐vinylpyrroles for the mild reaction conditions and readily available materials, compared with previously inaccessible N‐vinylpyrroles with electron‐withdrawing groups, especially these pyrroles bearing alkaline sensitive substitution groups.     

Aniline‐Promoted Cyclization–Replacement Cascade Reactions of 2‐Hydroxycinnamaldehydes with Various Carbonic Nucleophiles through In Situ Formed N,O‐Acetals

In this study, we report the harnessing of new reactivity of N,O‐acetals in an aminocatalytic fashion for organic synthesis. Unlike widely used strategies requiring the use of acids and/or elevated temperatures, direct replacement of the amine component of the N,O‐acetals by carbon‐centered nucleophiles for C?C bond formation is realized under mild reaction conditions. Furthermore, without necessary preformation of the N,O‐acetals, an amine‐catalyzed in situ formation of N,O‐acetals is developed. Coupling both reactions into a one‐pot operation enables the achievement of a catalytic process. We demonstrate the employment of simple anilines as promoters for the cyclization–substitution cascade reactions of trans‐2‐hydroxycinnamaldehydes with various carbonic nucleophiles including indoles, pyrroles, naphthols, phenols, and silyl enol ethers. The process offers an alternative approach to structurally diverse, “privileged” 2‐substituted 2H‐chromenes. The synthetic power of the new process is furthermore shown by its application in a 2‐step synthesis of the natural product candenatenin E and for the facile installation of 2‐substituted 2H‐chromene moieties into biologically active indoles.     

Copper‐catalyzed Clauson–Kass pyrroles synthesis in aqueous media

An efficient and convenient copper‐catalyzed Clauson–Kass reaction of 2,5‐dimethoxytetrahydrofuran with amines in aqueous media has been developed, providing a wide range of N‐substituted pyrroles in good yields. It is noteworthy that the Clauson–Kass reaction of 2,5‐dimethoxytetrahydrofuran with p‐phenylenediamine or m‐phenylenediamine proceeds smoothly to afford the corresponding monopyrroles and bispyrroles with high selectivity in impressive yields. A plausible mechanism for the formation of N‐substituted pyrroles has been proposed. Copyright © 2012 John Wiley & Sons, Ltd.     

Efficient and Green Synthesis of N‐aryl Pyrroles Catalyzed by Ionic Liquid [H‐NMP][HSO4] in Water at Room Temperature

A suitable and efficient method for the synthesis of N‐aryl pyrroles by using 2,5‐dimethoxy tetrahydrofuran and several primary aromatic amines in the presence of the catalytic amount of [H‐NMP][HSO₄] under room temperature was described. This method has the advantages such as; easy reaction workup, absolutely separated of catalyst from the reaction mixture and smoothly recyclability of catalyst. In this reaction, N‐substituted pyrroles were obtained as desired products in excellent yields and short reaction times via green and one‐pot procedure.     

Rhodium/Silver‐Cocatalyzed Transannulation of N‐Sulfonyl‐1,2,3‐triazoles with Vinyl Azides: Divergent Synthesis of Pyrroles and 2 H‐Pyrazines

The first cyclization reaction between vinyl azides and N‐sulfonyl‐1,2,3‐triazoles is reported. A Rh/Ag binary metal catalyst system proved to be necessary for the successful cyclization. By varying the structure of vinyl azides, such reaction allows the divergent synthesis of pyrroles and 2H‐pyrazines. The cyclization reactions feature a broad substrate scope, good functional group tolerance, high reaction efficiency, and good to high product yields.     

Latent Nucleophiles in Lewis Base Catalyzed Enantioselective N‐Allylations of N‐Heterocycles

Latent nucleophiles are compounds that are themselves not nucleophilic but can produce a strong nucleophile when activated. Such nucleophiles can expand the scope of Lewis base catalyzed reactions. As a proof of concept, we report that N‐silyl pyrroles, indoles, and carbazoles serve as latent N‐centered nucleophiles in substitution reactions of allylic fluorides catalyzed by Lewis bases. The reactions feature broad scopes for both reaction partners, excellent regioselectivities, and produce enantioenriched N‐allyl pyrroles, indoles, and carbazoles when chiral cinchona alkaloid catalysts are used.     

Selective and Efficient Formylation of Indoles (C3) and Pyrroles (C2) Using 2,4,6‐Trichloro‐1,3,5‐Triazine/Dimethylformamide (TCT/DMF) Mixed Reagent

This study introduces an efficient method for the selective formylation of indoles and pyrroles at the positions of C(3) and C(2), respectively. The mixture of three equivalents of N ,N‐dimethylformamide and one equivalent of 2,4,6‐trichloro‐1,3,5‐triazine (cyanuric chloride) generates an easy handling formylating agent for the efficient formylation of these classes of compounds to give the corresponding aldehydes under mild reaction conditions. This procedure was highly efficient, and a range of formylated indoles and pyrroles were obtained in good to excellent yields.     

Intramolecular Sulfenylation Using Sulfides Synthesis of 5H‐Pyrrolo[1,2‐a][3,1]benzothiazines

Treatment of N‐[2‐(methylsulfanylmethyl)aryl]pyrroles ( 4 ) with phenyliodine(III) bis(trifluoroacetate) containing trifluoroacetic acid resulted in an interrupted Pummerer‐type reaction to give 5H‐pyrrolo[1,2‐a][3,1]benzothiazines ( 5 ) rather than the normal Pummerer‐type products.     

Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions

The first highly diastereo‐ and enantioselective synthesis of five‐membered spiro‐2H‐pyrroles was achieved using an Ir‐catalyzed asymmetric allylic dearomatization reaction. The spiro‐2H‐pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir‐complex K1 , derived from [Ir(cod)Cl]₂ (cod=1,5‐cyclooctadiene) and N‐benzhydryl‐N‐phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo‐ and enantioselectivities.     

Base‐catalyzed condensation of thioglycolic ester with β‐chloropyrrolecarbaldehyde: One‐pot approach to substituted thieno[2,3‐b]pyrroles

A simple methodology has been developed for the synthesis of thieno[2,3‐b]pyrroles from N‐aryl‐diformylated‐pyrroles by base catalyzed condensation with thioglycolic ester. J. Heterocyclic Chem., 2011.     

Synthesis of 2‐Aryl‐5‐oxo‐4‐[2‐(phenylmethylidene)hydrazino]‐2,5‐dihydro‐1H‐pyrrole‐3‐carboxylates by the Reaction between Hydrazones,Acetylenedicarboxylates, and 1‐Aryl‐N,N′‐bis(arylmethylidene)methanediamines

An efficient approach for the preparation of functionalized 2‐aryl‐2,5‐dihydro‐5‐oxo‐4‐[2‐(phenylmethylidene)hydrazino]‐1H‐pyrroles is described. The four‐component reaction between aldehydes, NH₂NH₂?H₂O, dialkyl acetylenedicarboxylates, and 1‐aryl‐N,N′‐bis(arylmethylidene)methanediamines proceeds in EtOH under reflux in good‐to‐excellent yields (Scheme 1). The structures of 4 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS, and, in the case of 4f , by X‐ray crystallography). A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Catalytic Asymmetric Synthesis of Trifluoromethylated γ‐Amino Acids through the Umpolung Addition of Trifluoromethyl Imines to Carboxylic Acid Derivatives

Novel cinchona alkaloid derived chiral phase‐transfer catalysts enabled the highly chemo‐, regio‐, diastereo‐, and enantioselective umpolung addition of trifluoromethyl imines to α,β‐unsaturated N‐acyl pyrroles. With a catalyst loading ranging from 0.2 to 5.0 mol %, this new catalytic asymmetric transformation provides facile and high‐yielding access to highly enantiomerically enriched chiral trifluoromethylated γ‐amino acids and γ‐lactams.     

RhII‐Catalyzed [3+2] Cycloaddition of 2 H‐Azirines with N‐Sulfonyl‐1,2,3‐Triazoles

Rh^II‐catalyzed intermolecular [3+2] cycloaddition of 2 H‐azirines with N‐sulfonyl‐1,2,3‐triazoles is disclosed, in which a series of fully functionalized pyrroles is produced via rhodium azavinyl carbene intermediates. A distinct feature of this reaction is that the azavinyl carbene serves as a [2 C] equivalent, instead of as [1 C] or aza‐[3 C] synthons, which have been reported previously in cyclopropanations and [3+n] cycloadditions. Moreover, this methodology has also been successfully applied in the total synthesis of URB447 as well as the formal synthesis of Atorvastatin (Lipitor).     

Alkene‐Directed N‐Attack Chemoselectivity in the Gold‐Catalyzed [2+2+1]‐Annulations of 1,6‐Enynes with N‐Hydroxyanilines

Kinetically unstable nitrones are generated from gold‐catalyzed reactions of 1,6‐enynes with N‐hydroxyanilines, and subsequently trapped by tethered alkenes to furnish [2+2+1]‐annulations. Our experimental data reveal that such nitrones arise from atypical N‐attack chemoselectivity that is triggered by tethered alkenes to facilitate the key protodeauration reaction.     

One‐pot Regioselective Synthesis of Novel 1‐N‐Methyl‐spiro[2,3′]oxindole‐spiro[3,3″]‐1″‐N‐arylpyrrolidine‐2″,5″‐dione‐4‐arylpyrrolidines through Multicomponent 1,3‐Dipolar Cycloaddition Reaction of Azomethine Ylide

An atom economic and facile synthesis of novel dispiro–oxindole–pyrrolidines has been achieved via a three‐component tandem cycloaddition of azomethine ylide generated in situ from isatin and sarcosine by decarboxylative condensation with N‐aryl‐3‐benzylidene‐pyrrolidine‐2,5‐dione derivatives as dipolarophiles. The salient features of synthetic procedure are characterized by the mild reaction conditions, high yields, high regioselectivity and stereoselectivity, one‐pot procedure, and operational simplicity. This regioselectivity was assumed to be under the influence of π–π stacking interactions between the aromatic rings of azomethine ylide and N‐aryl‐3‐benzylidene‐pyrrolidine‐2,5‐diones that further control the exo–endo selectivity of the reaction 1,3‐dipolar cycloaddition. The regiochemistry and structures of the cycloadducts were determined with spectroscopic data.     

KOH‐Oriented Ring Openings of N‐Tosylaziridines with Carboxylic Acids in DMSO

A facile and efficient KOH‐oriented regioselective ring‐opening reaction for the acetolysis of N‐tosylaziridines in DMSO was developed under mild conditions. This operationally simple protocol could tolerate a variety of functionalized carboxylic acids as well as several N‐tosylaziridines. Moreover, this strategy provided the corresponding ring‐opening products with good results.     

A Practical One‐Step Synthesis of 1,2‐Oxazoline Derivatives from Unprotected Sugars and Its Application to Chemoenzymatic β‐N‐Acetylglucosaminidation of Disialo‐oligosaccharide

A facile and practical method for synthesis of sugar oxazolines (=dihydrooxazoles) from the corresponding N‐acetyl‐2‐amino sugars has been developed by using 2‐chloro‐1,3‐dimethyl‐1H‐benzimidazol‐3‐ium chloride (CDMBI) as a dehydrative condensing agent. The intramolecular dehydrative reaction between the 2‐acetamido group and the anomeric OH group of unprotected N‐acetyl‐2‐amino sugars took place smoothly in H₂O, leading to the formation of a 1,2‐oxazoline (=4,5‐dihydrooxazole) moiety in good yield. Since the reaction proceeds in H₂O without using any protecting groups, the resulting oxazolines can be utilized as effective glycosyl donors for the subsequent enzymatic glycosylation. We have successfully demonstrated a highly efficient chemoenzymatic transglycosylation of a disialo‐oligosaccharide moiety to p‐nitrophenyl N‐acetylglucosaminide catalyzed by a mutant endo‐N‐acetylglucosaminidase without isolating disialo‐oligosaccharide oxazoline as synthetic intermediate.     

Synthesis of Highly Substituted N‐(Furan‐3‐ylmethylene)benzenesulfonamides by a Gold(I)‐Catalyzed Oxidation/1,2‐Alkynyl Migration/Cyclization Cascade

A variety of N‐(furan‐3‐ylmethylene)benzenesulfonamides were obtained by a gold(I)‐catalyzed cascade reaction from easily accessible starting materials. The reaction pathway involves a rarely observed 1,2‐alkynyl migration onto a gold carbenoid. This observation further enriches gold carbenoid chemistry with regard to group migration.     

Umpolung Reactivity of Ynamides: An Unconventional [1,3]‐Sulfonyl and [1,5]‐Sulfinyl Migration Cascade

A regioselective sulfonyl/sulfinyl migration cycloisomerization cascade of alkyne‐tethered ynamides is developed in the presence of XPhosgold catalyst. This reaction is the first example of a general [1,3]‐sulfonyl migration from the nitrogen center to the β‐carbon atom of ynamides, followed by umpolung 5‐endo‐dig cyclization of the ynamide α‐carbon atom to the gold‐activated alkyne, and final deaurative [1,5]‐sulfinylation. This process allows the synthesis of peripherally decorated unconventional 4‐sulfinylated pyrroles with broad scope from N‐propargyl‐tethered ynamides. In contrast, N‐homopropargyl‐tethered ynamides undergo intramolecular tetradehydro Diels–Alder reaction to provide 2,3‐dihydro‐benzo[f]indole derivatives. Control experiments and density‐functional theory studies were used to study the reaction pathways.     

Reagent‐free and pH‐independent degradation of N‐nitrosamines using electrons generated via corona discharge at ambient pressure

Traditional degradation methods for N‐nitrosamines are either confined with acid solution or required for additional chemical reagents to guarantee high reaction efficiency. Herein, we demonstrate a facile and effective way for reagent‐free and pH‐independent degradation of N‐nitrosamines, which was induced by free electrons generated via corona discharge at ambient pressure. The highly reactive free electron is produced in situ and responsible for degradation of three N‐nitrosamines, which was also theoretically confirmed. N‐nitrosamines were believed to be reduced by electrons and to form the radical anion, which underwent a selectively heterolytic cleavage of the N–NO bonds to form the corresponding secondary amines as the degradation products.