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.     

Insertion of Nitriles into Zirconocene 1‐aza‐1,3‐diene Complexes: Chemoselective Synthesis of N–H and N‐Substituted Pyrroles

The direct insertion of nitriles into zirconocene‐1‐aza‐1,3‐diene complexes provides an efficient, chemoselective, and controllable synthesis of N‐H and N‐substituted pyrroles upon acidic aqueous work‐up. The outcome of the reaction (that is, the formation of N‐H or N‐substituted pyrroles) results from the different cyclization patterns, which depend on the relative stability and reactivity of the enamine–imine tautomers formed by hydrolysis of the diazazirconacycles.     

Nickel(0)‐Catalyzed Hydroarylation of Styrenes and 1,3‐Dienes with Organoboron Compounds

A Ni‐catalyzed hydroarylation of styrenes and 1,3‐dienes with organoboron compounds has been developed. The reaction offers a highly selective approach to diarylalkanes and allylarenes under redox‐neutral conditions. In this hydroarylation reaction, a new strategy that uses the proton of methanol to generate the active catalyst species Ni?H was developed. The Ni‐catalyzed hydroarylation, combined with a Ir‐catalyzed C?H borylation, affords a very efficient and straightforward access to a retinoic acid receptor agonist.     

Retracted: A Facile Synthetic Route to New Fluorinated Building‐Blocks of 1‐Fluoroalkynes and 1‐Fluorodiynes

A facile and direct fluorination process of alkynes and diynes was developed. In the presence of n‐butyllithium, the reaction of a series of terminal alkynes and diynes with the electrophilic fluorinating reagent (NFSI) proceeded to afford various 1‐fluoroalkynes and 1‐fluoro‐1,3‐diynes in moderate to high 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.     

Divergent Reactivity in Palladium‐Catalyzed Annulation with Diarylamines and α,β‐Unsaturated Acids: Direct Access to Substituted 2‐Quinolinones and Indoles

A palladium‐catalyzed C?H activation strategy has been successfully employed for exclusive synthesis of a variety of 3‐substituted indoles. A [3+3] annulation for synthesizing substituted 2‐quinolinones was recently developed by reaction of α,β‐unsaturated carboxylic acids with diarylamines under acidic conditions. In the present work, an analogous [3+2] annulation is achieved from the same set of starting materials under basic conditions to generate 1,3‐disubstituted indoles exclusively. Mechanistic studies revealed an ortho‐palladation–π‐coordination–β‐migratory insertion–β‐hydride elimination reaction sequence to be operative under the reaction conditions.     

Highly N2‐Selective Coupling of 1,2,3‐Triazoles with Indole and Pyrrole

Hydrogen‐bond mediated coupling of 1,2,3‐triazoles to indoles and pyrroles results in N2 selective functionalization of the triazole moiety in moderate to excellent yields. The reaction was tolerant of un‐, mono‐ and disubstituted triazoles and was applied to synthesize tryptophan derived fluorescent amino acids.     

Synthesis of Unsymmetrical 1,3‐Diynes via Pd/Cu‐Catalyzed Cross‐Coupling of Terminal Alkynes at Room Temperature

A facile and practical synthetic route of unsymmetrical 1,3‐diynes via the PdCl/CuI catalyzed oxidative coupling of two different terminal alkynes has been developed by using 3‐(diphenylphosphino)propanoic acid as a ligand in the presence of oxygen. This system is suitable for not only aromatic alkynes but also heteroaromatic and aliphatic alkynes which were transformed into the corresponding unsymmetrical 1,3‐diynes in moderate to good yields at room temperature. Moreover, the unsymmetrical 1,3‐diynes were also obtained on a multi‐gram scale. Mechanistic studies suggest that oxygen plays a key role in the catalytic cycles.     

CuI‐catalyzed homocoupling of terminal alkynes to 1,3‐diynes

A simple and efficient protocol for CuI‐catalyzed oxidative homocoupling reaction of terminal alkynes to symmetrical 1,4‐disubstituted 1,3‐diynes was reported. The reaction can be carried out in the open air, using NaOAc as a base in the absence of any other additives. A variety of terminal alkynes were converted to the corresponding 1.3‐diynes in good to excellent yields without any side product formation. Copyright © 2010 John Wiley & Sons, Ltd.     

Highly Efficient Cycloaddition Reaction of 1,3‐Diynes with Sodium Azide: A New Way to 5‐Substituted‐4‐acetylene‐1H‐1,2,3‐triazoles

A cycloaddition reaction of a range of 1,3‐diynes with sodium azide has been realized, which provided 5‐substituted‐4‐acetylene‐1H‐1,2,3‐triazoles in 75–99% yields. The chemical structures of the new compounds 3 are established by IR, NMR, Mass, and HRMS.     

Nickel(II)‐Catalyzed Diastereo‐ and Enantioselective [3+2] Cycloaddition of α‐Ketoesters with 2‐Nitrovinylindoles and 2‐Nitrovinylpyrroles

The catalytic asymmetric [3+2] cycloaddition of α‐ketoesters with 2‐nitrovinylindoles and 2‐nitrovinyl‐ pyrroles has been established. This strategy allowed the construction of structurally diverse pyrrolo[1,2‐a]indoles bearing three contiguous stereocenters in generally high yields and good to excellent stereoselectivities (up to 98% yield, > 98 : 2 dr, 99% ee). The efficient synthesis of tetracyclic psychotropic compound analogue via the derivatization of cycloadduct showed the great synthetic potential of this strategy.     

Multicomponent Reactions of Pyridines To Give Ring‐Fused Pyridiniums: In Situ Activation Strategy Using 1,2‐Dichloroethane as a Vinyl Equivalent

Reported herein is a rhodium(III)‐catalyzed three‐component annulation reaction of simple pyridines, alkynes, and 1,2‐dichloroethane (DCE), affording a streamlined pathway to diverse ring‐fused pyridiniums. DCE not only serves as a vinyl equivalent but also as an in situ activating agent for pyridine C2?H activation. A cationic five‐membered rhodacycle complex has been isolated and proposed as a possible intermediate. This strategy can be extended to other N‐containing heteroarenes for the synthesis of multiring‐fused pyridiniums. These multicomponent reactions exhibit excellent regioselectivity for 1,3‐diynes, paving a path to the cascade cyclization of 3‐fluoropyridine or N‐methylpyridin‐3‐amine with 1,3‐diynes for the construction of brand‐new tricyclic‐fused pyrano‐ or hydropyridoquinolizinium salts. These ionic fluorophores have been investigated as potential biomarkers.     

One‐step ring‐closure procedure for 4,5‐dihydro‐1,3‐thiazino[5,4‐b]indole derivatives with Lawesson's reagent. The fifth dihydro‐1,3‐thiazino[b]indole isomer

We report a convenient approach for the synthesis of a new ring system: 4,5‐dihydro‐1,3‐thiazino[5,4‐b]indoles. The procedure involves the use of Lawesson's reagent in the presence of silica to achieve the one‐step ring‐closure reactions of 2‐benzoylamino‐3‐hydroxymethylindole intermediates to furnish 4,5‐dihydro‐2‐aryl‐1,3‐thiazino[5,4‐b]indoles. 2‐Phenylimino‐1,3‐thiazino[5,4‐b]indoles were obtained via the corresponding 3‐phenylthiourea‐2‐carboxylic acid ester derivatives by chemoselective reduction of the ester group, followed by ring closure under acidic conditions. The structures of the novel products were elucidated by IR, ¹H‐NMR, and ¹³C‐NMR spectroscopy, including 2D‐HMQC, 2D‐HMBC, and DEPT measurements. J. Heterocyclic Chem., (2011).     

Ruthenium‐Catalyzed Functionalization of Pyrroles and Indoles with Propargyl Alcohols

Several ruthenium‐catalyzed atom‐economic transformations of propargyl alcohols with pyrroles or indoles leading to alkylated, propargylated, or annulated heteroaromatics are reported. The mechanistically distinct reactions are catalyzed by a single ruthenium(0) complex containing a redox‐coupled dienone ligand. The mode of activation regarding the propargyl alcohols determines the reaction pathway and depends on the alcohols’ substitution pattern. Secondary substrates form alkenyl complexes by a 1,2‐hydrogen shift, whereas the transformation of tertiary substrates involves allenylidene intermediates. 1‐Vinyl propargyl alcohols are converted by a cascade allylation/cyclization sequence. The environmentally benign processes are of broad scope and allow the selective synthesis of highly functionalized pyrroles and indoles generating water as the only waste product.     

Cross‐Cycloaddition of Two Different Isocyanides: Chemoselective Heterodimerization and [3+2]‐Cyclization of 1,4‐Diazabutatriene

A new cross‐cycloaddition reaction between a wide range of isocyanides and 2‐isocyanochalcones (or analogues) was developed for the expeditious synthesis of pyrrolo[3,4‐b]indoles under thermal conditions. On the basis of the experimental results and DFT calculations, a mechanism for this domino reaction is proposed involving chemoselective heterodimerization of two different isocyanides to form 1,4‐diazabutatriene intermediates, followed by an intramolecular [3+2]‐cycloaddition and 1,3‐proton shift.     

Synthesis of pyrazole‐fused azepino[5,4,3‐cd]indoles

The synthesis of some new pyrazolo[3′,4′:6,7]azepino[5,4,3‐cd] indoles (10a‐c) was achieved via regios‐elective cyclization of the respective 3‐(4‐acylaminopyrazol‐5‐yl)indoles (9a‐c) under Bischler‐Napieralski reaction conditions. The latter compounds were obtained by acylation of the corresponding 3‐(4‐aminopyra‐zol‐5‐yl)indoles (8a,b) which, in turn, were prepared by reduction of the 3‐(4‐nitropyrazol‐5‐yl)indoles precursors (7a,b) . The latter synthons were accessible from the reaction of indolylzinc chlorides (5a,b) with 5‐chloro‐1,3‐dimethyl‐4‐nitropyrazole. Ms and nmr spectral data of 10a‐c are in agreement with the assigned azepino‐indole structure as determined for 10a by X‐ray crystal measurements which demonstrate that the azepine ring is almost completely planar with the indole and pyrazole rings.     

Access to Indoles via Diels–Alder Reactions of 5‐Methylthio‐2‐vinylpyrroles with Maleimides

Diels–Alder reactions of 5‐methylthio‐2‐vinyl‐1H‐pyrroles with maleimides followed by isomerization gave tetrahydroindoles in moderate to good yield. Aromatization using activated MnO₂ in refluxing toluene gave the corresponding 2‐methylthioindoles in good yields, and demethylthioation using Raney nickel gave the 2‐H indoles in excellent yields. The protection of the adducts produced aromatization in improved yield, demonstrating the effectiveness of the methylthio group as a protecting group for pyrroles; however, 5‐methylthio‐2‐vinylpyrrole was shown to perform with slightly less efficiency than 2‐vinylpyrrole in Diels–Alder reactions, indicating the protective group was more deactivating than desired. This route toward indoles offers high convergency and conveniently available starting materials that are easily purified. Bis‐methylthioated vinylpyrroles were shown to have potential as highly activated Diels–Alder dienes.     

Azocinoindole Synthesis by a Gold(I)‐Catalyzed Ring Expansion of 2‐Propargyl‐β‐Tetrahydrocarboline

A new methodology taking advantage of gold(I)‐catalyzed ring expansion has been developed to assemble tricyclic 1H‐azocino[5,4‐b]indoles from 2‐propargyl‐β‐tetrahydrocarbolines. The azocinoindoles were obtained in moderate to excellent yields; the structure of which was established by X‐ray crystallographic analysis. A mechanism involving regioselective intramolecular hydroarylation, [1,2]‐alkenyl migration and carbon–carbon bond‐fragmentation was proposed.     

Synthesis of vinylpyrroles, vinylfurans and vinylindoles via a Brønsted acid catalyzed highly regio- and stereoselective cis-hydroarylation of ynamides

A highly regio- and stereoselective Brønsted acid-catalyzed coupling of ynamides and aromatic heterocycles, such as pyrroles, furans, and indoles is described. This process is the equivalent of hydroarylation of ynamides, and leads to the efficient syntheses of an array of vinylheterocycles. Diels-Alder reaction between the vinylindoles and DMAD afforded carbazole derivatives in good yields.     

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.