Palladium and copper cocatalyzed tandem N-H/C-H Bond functionalization: synthesis of CF3-containing indolo- and pyrrolo[2,1-a]isoquinolines

A palladium- and copper-catalyzed tandem N-H/C-H bond functionalization reaction of ortho-(2-chlorovinyl)bromobenzenes with indoles and pyrroles has been developed. A variety of CF(3)-containing indolo- and pyrrolo[2,1-a]isoquinolines were prepared in moderate to good yields via the cyclization of 1-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-enyl)benzenes with indoles and pyrroles.     

Facile,efficient and eco-friendly synthesis of 5-sulfenyl tetrazole derivatives of indoles and pyrroles

A concise, two-step eco-friendly approach towards the synthesis of 5-sulfenyl tetrazole derivatives of indoles and pyrroles, is reported. The synthesis comprises the oxone-mediated thiocyanation of the starting heterocycles towards intermediate 3-thiocyanato indoles and 2-thiocyanato pyrroles, and their subsequent treatment with sodium azide in 2-propanol/water under zinc bromide promotion.     

Sulfenylation of some pyrroles and indoles

Methylsulfenylation of 1-substituted pyrroles and indoles was observed using 1-(methylthio)morpholine and an acid catalyst or with methylsulfenyl chloride and excess pyridine. 1-Substituents which are activating or weakly deactivating towards electrophilic substitution such as alkyl, 2-cyanoethyl, dimethylamino, trialkylsilyl, 2-chloroethyl and 2-phenylsulfonylethyl were used. The 2-chloroethyl and 2-phenylsulfonylethyl groups which can be removed with a strong base can be used to obtain 1H-methylthiopyrroles and indoles. 1-Phenylsulfonyl and 1-acetyl substituents are too strongly deactivating for these sulfenylations to be successful. Mono and disubstituted pyrroles and monosubstituted indoles can be isolated from these reactions, however, because the methylthio group is activating towards electrophilic substitution the main advantage of these reactions is the synthesis of tri and tetrasubstituted pyrroles and disubstituted indoles. 1-Methyl-2,3,4,5-tetra-methylthiopyrrole and 1-methyl-2,3-dimethylthioindole are oxidized to the corresponding 3,4-disulfoxide and 3-sulfoxide and with excess oxidizing agent to the tetrasulfone and disulfone, respectively.     

Formal [4+2] Reaction between 1,3‐Diynes and Pyrroles: Gold(I)‐Catalyzed Indole Synthesis by Double Hydroarylation

Indole synthesis by a gold(I)‐catalyzed intermolecular formal [4+2] reaction between 1,3‐diynes and pyrroles has been developed. This reaction involves the hydroarylation of 1,3‐diynes with pyrroles followed by an intramolecular hydroarylation to give the 4,7‐disubstituted indoles. This reaction can also be applied to the synthesis of carbazoles when indoles are used as the nucleophiles instead of pyrroles.     

Arylsulfenylation of heterocyclic compounds with arylsulfenamides in the presence of phosphorus(V) oxochloride

The electrophilic sulfenylation of a series of indoles and pyrroles with arylsulfenamides in the presence of phophorus(V) oxohalide has been studied. It has been shown that arylsulfenylation of indoles led to products with substitution at position 3, while in the case of pyrrole it occurred at position 2.     

Novel gallium-mediated C3-allylation of indoles and pyrroles in aqueous media promoted by Bu4NBr

A mild and efficient protocol for the coupling of indoles and pyrroles with allyl halides such as allyl bromide, crotyl bromide and propargyl bromide in the presence of gallium metal in a Bu₄NBr-DMF-H₂O system has been developed. The reaction is equally effective when cadmium is used in lieu of gallium and the corresponding 3-allyl indoles and 3-allyl pyrroles were obtained in almost comparable yields.     

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.     

Triflic acid-catalyzed highly stereoselective friedel-crafts aminoalkylation of indoles and pyrroles

A simple and efficient synthesis to both enantiomers of highly enantiomerically enriched alpha-trifluoromethyl-alpha-(heteroaryl)-glycine derivatives via highly stereoselective aminoalkylation of indoles and pyrroles is described. The triflic acid-catalyzed reaction of enantiomeric 3,3,3-trifluoro-pyruvate-alpha-methylbenzyl imines with indoles and pyrroles and the subsequent Pd-catalyzed hydrogenolysis of the methylbenzyl group provided the products in high yields and excellent enantioselectivities.     

Gold(I)-catalyzed rearrangement of 3-silyloxy-1,5-enynes: an efficient synthesis of benzo[b]thiophenes, dibenzothiophenes, dibenzofurans, and indole derivatives

With the IPr ligand (IPr=1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene) on gold(I) excellent yields in the benzanellation of 2-substituted thiophenes, benzothiophenes, pyrroles, benzofurans, and indoles were achieved. The 1-siloxybut-3-ynyl side chains, incorporated in the anellation, are easily accessible by the addition of a propargyl metal reagent to a formyl group and silylation of the alcohol. This conveniently allows an anellation at the position of the formyl group under mild conditions. All reactions involve a 2,3-shift of the side chain in the anellation step and thus, provide an easy access to specific substitution patterns. Only in the case of 2-substituted indoles with their highly nucleophilic 3-position a direct hydroarylation without shift is observed. On the other hand, 3-substituted indoles give the same products as 2-substituted indoles. Then, a 3,2-shift in the indole ring system has to be involved.     

Gold(I)‐Catalyzed Rearrangement of 3‐Silyloxy‐1,5‐enynes: An Efficient Synthesis of Benzo[b]thiophenes,Dibenzothiophenes, Dibenzofurans,and Indole Derivatives

With the IPr ligand (IPr=1,3‐bis‐(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) on gold(I) excellent yields in the benzanellation of 2‐substituted thiophenes, benzothiophenes, pyrroles, benzofurans, and indoles were achieved. The 1‐siloxybut‐3‐ynyl side chains, incorporated in the anellation, are easily accessible by the addition of a propargyl metal reagent to a formyl group and silylation of the alcohol. This conveniently allows an anellation at the position of the formyl group under mild conditions. All reactions involve a 2,3‐shift of the side chain in the anellation step and thus, provide an easy access to specific substitution patterns. Only in the case of 2‐substituted indoles with their highly nucleophilic 3‐position a direct hydroarylation without shift is observed. On the other hand, 3‐substituted indoles give the same products as 2‐substituted indoles. Then, a 3,2‐shift in the indole ring system has to be involved.     

Easy formation of SNH products in reactions of indoles and pyrroles with 3-aryl-1,2,4-triazin-5(2H)-ones in the presence of tosyl chloride

The reactions of 3-aryl-1,2,4-triazin-5(2H)-ones with indoles and pyrroles in the presence of p-toluenesulfonyl chloride afforded 3-aryl-6-hetaryl-1,2,4-triazin-5(2H)-ones in high yields. The latter are products of the nucleophilic substitution of hydrogen.     

The highly enantioselective addition of indoles and pyrroles to isatins-derived N-Boc ketimines catalyzed by chiral phosphoric acids

The first asymmetric aza-Friedel-Crafts reaction of indoles and pyrroles with isatin-derived N-Boc ketimines catalyzed by chiral phosphoric acids is reported. In general, derivatives of substituted 3-amino-2-oxindoles were obtained with excellent enantioselectivities and high yields.     

From Heteroaromatic Acids and Imines to Azaspirocycles: Stereoselective Synthesis and 3D Shape Analysis

Heteroaromatic carboxylic acids have been directly coupled with imines using propylphosphonic anhydride (T3P) and NEt(iPr)₂ to form azaspirocycles via intermediate N‐acyliminium ions. Spirocyclic indolenines (3H‐indoles), azaindolenines, 2H‐pyrroles and 3H‐pyrroles were all accessed using this metal‐free approach. The reactions typically proceed with high diastereoselectivity and 3D shape analysis confirms that the products formed occupy areas of chemical space that are under‐represented in existing drugs and high throughput screening libraries.     

Regioselective synthesis of 3-heteroarylpiperidin-2-ones and diazacyclopenta[a]phenalenone via carbenoid reactions

Rhodium(II) catalyzed carbenoid reactions of 3-diazopiperidin-2-ones were carried out with indoles and pyrroles to afford the respective (3-indol-3-yl)- and (3-pyrrol-2-yl)piperidones with regioselectivity. Interestingly, the reaction of bis-diazoimide in the presence of Rh₂(OAc)₄ catalyst furnished diazacyclopenta[a]phenalenone in a tandem manner.     

Photoinduced chlorine atom-transfer cyclization/photohydrolysis of 3-acyl-2-chloro-N-(ω-phenylalkynyl)pyrroles: a one-pot synthesis of benzoyl-substituted fused pyrroles

A one-pot synthesis of benzoyl-substituted fused pyrroles or indoles in moderate to high yields has been achieved by the photocyclization/photohydrolysis reactions of N-(ω-phenylalkynyl)-2-chloropyrrole-3-carbaldehydes or 3-acyl-N-(ω-phenylbutynyl)-2-haloindoles in wet acetone. The formation of all these products could be inferred by a two-step reactions, namely, photoinduced chlorine atom-transfer cyclization and subsequent photohydrolysis.     

Et3B-Mediated radical alkylation of pyrroles and indoles

An efficient Et₃B-mediated oxidative radical substitution of substituted pyrroles and indoles using xanthate based radical chemistry in the presence of iron(II) sulfate is described. Unsubstituted indole gave only low yield or failed in the process. 2-Cyanofuran and 2-benzoylthiophene did not afford the corresponding alkylated products under these conditions.     

A rapid stereoselective C-glycosidation of indoles and pyrrole via indium trichloride promoted reactions of glycosyl halides

Various C-glycosyl indoles and pyrroles were synthesized within a few minutes through coupling acetobromo sugars with suitably substituted indoles and pyrrole in the presence of catalytic amounts of InCl₃ at room temperature. Most of the glycosylations proceeded with a high stereoselectivity.     

Novel and direct oxidative cyanation reactions of heteroaromatic compounds mediated by a hypervalent iodine(III) reagent

The hypervalent iodine(III) reagent phenyliodine bis(trifluoroacetate) (PIFA) mediates the selective cyanation reactions of a wide range of electron-rich heteroaromatic compounds such as pyrroles, thiophenes, and indoles under mild conditions. These reactions proceed via a cation radical intermediate, and the key for the successful transformation presumably depends on the oxidation-reduction potential of the substrates used. The synthetic utility has been demonstrated through the conversion of these biologically important pyrroles 2f and 2g. [reaction: see text]     

Direct C-H arylation of (hetero)arenes with aryl iodides via rhodium catalysis

A new method for the catalytic C-H arylation of heteroarenes and arenes that manifests high activity paired with reasonably broad scope was developed. Under the catalytic influence of RhCl(CO){P[OCH(CF3)2]3}2 and Ag2CO3, the direct C-H arylation of heteroarenes/arenes with aryl/heteroaryl iodides took place to afford a range of biaryls in good to excellent yields with high regioselectivity. Thiophenes, furans, pyrroles, indoles, and alkoxybenzenes are applicable in this arylation protocol.     

Synthesis of indoloand pyrroloquinazolones

2-Quinazolone reacts with various π-surplus systems (indoles and pyrroles) to give 3,4-dihydro-4-substituted 2-quinazolones. These compounds are capable of oxidation to 4-substituted 2-quinazolones. o-Carbamidobenzylideneurea gives identical products in these reactions.