Efficient Microwave-assisted One-pot Three-component Synthesis of 2,3-Disubstituted Benzofurans under Sonogashira Conditions.

An efficient one-pot method for the synthesis of 2,3-disubstituted benzo[b]furans from commercially available 2-iodophenols, terminal acetylenes and aryl iodides has been developed utilizing Sonogashira reaction conditions. After an initial Sonogashira coupling of the 2-iodophenol with the terminal alkyne, cyclization involving the aryl iodide provides the 2,3-disubstituted benzo[b]furan in good to excellent yields. The use of microwave irradiation shortens the reaction times and minimizes the side products. This methodology is especially useful for the construction of libraries of highly substituted benzo[b]furans and their analogues.

Use of benzynes for the synthesis of heterocycles.

About two decades after Kobayashi's discovery in 1983 of a very mild way of generating highly reactive aryne intermediates, the synthetic community embraced o-(trimethylsilyl)aryl triflates as convenient and versatile aryne precursors for the synthesis of carbocycles and heterocycles, as well as natural products and pharmaceutically promising drug candidates. This review provides a comprehensive overview of the construction of heterocycles using Kobayashi's silylaryl triflate aryne precursors. It is organized according to the type of heterocycle generated.

Synthesis of N-acylcarbazoles through palladium-catalyzed aryne annulation of 2-haloacetanilides.

N-Acylcarbazoles have been synthesized in moderate to good yields by the annulation of in situ generated arynes with 2-haloacetanilides in the presence of a palladium catalyst and CsF. Both C-C and C-N bonds are formed simultaneously, and a variety of functional groups are tolerated in this reaction.

One-pot synthesis of 1-alkyl-1H-indazoles from 1,1-dialkylhydrazones via aryne annulation.

The reaction of readily accessible 1,1-dialkylhydrazones with commercially available o-(trimethylsilyl)aryl triflates provides a direct one-step route to pharmaceutically important 1-alkylindazoles. The products are obtained in high yields by one-pot NCS-chlorination/aryne annulation or Ac(2)O-acylation/deprotection/aromatization protocols.

Synthesis of pyrido[1,2-a]indole malonates and amines through aryne annulation.

Pyrido[1,2-a]indoles are known as medicinally and pharmaceutically important compounds, but there is a lack of efficient methods for their synthesis. We report a convenient and efficient route to these privileged structures starting from easily accessible 2-substituted pyridines and aryne precursors. A small library of compounds has been synthesized utilizing the developed method, affording variously substituted pyrido[1,2-a]indoles in moderate to good yields.

Iodocyclization, followed by palladium-catalyzed coupling: a versatile strategy for heterocyclic library construction.

The iodocyclization of functionally-substituted alkynes provides an excellent way to prepare a wide range of iodoheterocycles, which can then be readily elaborated through palladium-catalyzed Suzuki-Miyaura, Sonogashira, Heck, Hartwig-Buchwald, and carbonylation processes into libraries of medicinally relevant heterocycles. The synthesis of libraries of indoles, benzofurans, benzothiophenes, isocoumarins and pyrones, cyclic imidates, isoxazoles, furans using this approach is reviewed. This technology is very versatile, proceeds under mild reaction conditions in high yields, and tolerates considerable functionality.

Solution-phase parallel synthesis of a diverse library of 1,2-dihydroisoquinolines.

Synthesis of a 105 membered library of 1,2-dihydroisoquinolines is described. The 1,2-dihydroisoquinoline compounds have been prepared in good yields using a Lewis acid and organocatalyst-cocatalyzed multicomponent reaction of 2-(1-alkynyl)benzaldehydes, amines, and ketones. Various indoles have also been employed as pronucleophiles, furnishing 1-(3-indolyl)-1,2-dihydroisoquinolines. The halogen functionality present in some of the synthesized compounds allows for further diversification by palladium-catalyzed Suzuki−Miyaura and Sonogashira cross-couplings to give more diversified 1,2-dihydroisoquinoline derivatives.

An Efficient, Microwave-Assisted, One-Pot Synthesis of Indoles Under Sonogashira Conditions.

A microwave-assisted, one-pot, three-component coupling reaction for the synthesis of indoles has been developed. The reaction is carried out in two steps under standard Sonogashira coupling conditions from an N-substituted/N,N-disubstituted 2-iodoaniline and a terminal alkyne, followed by the addition of acetonitrile and an aryl iodide. A variety of polysubstituted indoles have been prepared in moderate to excellent yields using the present method.