A formal vinylic substitution reaction for the synthesis of α,ß-unsaturated enol esters and their anticancer potential.

Arylsulfonyl group-bearing α,ß-unsaturated enol esters were readily assembled via the Cs2CO3-mediated union of 2-bromoallyl sulfones and cinnamic acids. The overall transformation is equivalent to an sp2 carbon-oxygen coupling reaction, and therefore constitutes a formal vinylic substitution. Several of the products display promising levels of antiproliferative activities higher than that of the anticancer drug carboplatin. Thiophenol reacted with 2-bromoallyl sulfones under identical conditions to afford α-thiophenyl-α'-tosyl acetone via an apparent aerial oxidation.

Benzannulation Reactions: A Case for Perspective Change From Arene Decoration to Arene Construction.

Benzannulation reactions involve construction of a benzene ring from acyclic precursors. This class of reactions offer a versatile and often superior alternative to aromatic substitution for construction of substituted arenes. Selected pioneering and recent reports of various benzannulation reactions are categorised and discussed in this review.

Recent developments in the chemistry of allenyl sulfones.

Allenyl sulfones are versatile building blocks that readily partake in a variety of transformations such as Michael additions, rearrangements, cycloadditions, electrophilic additions and redox reactions. Selected recent developments in the preparation and various reactions of allenyl sulfones are presented.

Regioselective synthesis of arylsulfonyl heterocycles from bromoallyl sulfones via intramolecular Heck coupling reaction.

Indoles, benzofurans and benzosultams endowed with arylsulfonyl groups were prepared in two steps from 2-bromoallyl sulfones. ortho-Halosulfonamides and ortho-iodophenol reacted with 2-bromoallyl sulfones in the presence of cesium carbonate to furnish products resulting from a formal vinylic substitution reaction. Palladium-catalyzed intramolecular Heck reaction of these adducts furnished sulfonylated indoles, benzosultams and benzofurans. Isomerization of the double bond participating in the Heck reaction under basic conditions led to the formation of two isomeric products in two cases. Conditions for selectively accessing each of the regioisomeric indoles were developed.

Nucleophile-Initiated Catalytic and Multicomponent Reactions.

A number of well-known reactions, proceed through the intermediacy of dipolar/zwitterionic species generated via the addition of a neutral nucleophile with an unsaturated electrophile. A mechanistic understanding of these reactions was made possible by seminal contributions of Huisgen. The design of novel reactions based on such dipolar species was, however, not pursued in detail for a long time. Our efforts to exploit various reactivity profiles available for the zwitterionic/dipolar intermediates have resulted in the discovery of a large number of novel, convenient protocols to access a wide variety of products. The nucleophilic initiators may participate in the reaction or play a mediating role depending upon the nature of nucleophile, its quantity and the reaction conditions. In a majority of these transformations two electrophilic components, that would normally be inert towards each other, are combined by the intermediacy of a nucelophile. A brief summary of such nucleophile-initiated novel reactions that were developed in our research group are described. Reactions involving a variety of nucleophiles such as phosphines, pyridine, quinoline, isoquinoline, isocyanides, dimethoxycarbene and N-heterocyclic carbenes (NHCs) are discussed.

Facile synthesis of biarylmethanes and tetrasubstituted arenes via a base-mediated [3 + 3] benzannulation reaction of Morita-Baylis-Hillman adducts and unsaturated sulfones.

A facile DBU-mediated [3 + 3] benzannulation reaction of 1,3-bis-sulfonyl propenes and Morita-Baylis-Hillman (MBH) bromides is described. The benzannulation reaction afforded bis-sulfonyl biarylmethanes/arenes with complete regioselectivity. The products may be converted readily into corresponding benzophenones via site-selective benzylic oxidation.

Gold-catalysed regioselective cascade cycloisomerisation reactions of aza-enediynes for the synthesis of substituted benzoisoquinoline derivatives.

Aza-enediynes underwent a facile, regioselective gold-catalysed cascade cycloisomerisation to furnish dihydrobenzo[f]isoquinoline derivatives in excellent yields. The aza-enediynes were conveniently prepared via a formal vinylic displacement reaction of allyl bromosulfones. The latter functioned as a stable and easily accessible synthetic equivalent of allenyl sulfone.

Recent advances in employing homoenolates generated by N-heterocyclic carbene (NHC) catalysis in carbon-carbon bond-forming reactions.

The use of NHCs for generating homoenolate species has gained widespread popularity in recent years. A number of highly stereoselective processes of NHC-homoenolates have emerged. Homoenolate reactions have also been employed as key steps in the total synthesis of a number of natural products. The use of compatible co-catalysts, improved NHC-catalyst design and the use of novel precursors for homoenolate generation are among the major developments in this area that were disclosed recently. This tutorial review organises and presents the advancements in this rapidly growing area of catalysis and in the process updates a previous account published in 2011 in this journal.

Correction: Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions.

[This corrects the article DOI: 10.3762/bjoc.12.47.].

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions.

N-Heterocyclic carbenes (NHCs) have emerged as a powerful class of organocatalysts that mediate a variety of organic transformations. The Benzoin reaction constitutes one of the earliest known carbon-carbon bond-forming reactions catalysed by NHCs. The rapid growth of NHC catalysis in general has resulted in the development of a variety of benzoin and benzoin-type reactions. An overview of such NHC-catalysed benzoin reactions is presented.

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones.

The cesium carbonate-mediated reaction of 2-bromoallyl sulfones and ortho-hydroxychalcones furnished 3-arylsulfonyl-4H-chromene derivatives in 58-67% yield (18 examples). 2-Bromoallyl sulfones functioned as synthetic surrogates for allenyl sulfones in the reaction.

Base-Mediated Cyclocondensation of Salicylaldehydes and 2-Bromoallyl Sulfones for the Synthesis of 3-Sulfonylchromene Derivatives and Their Regioselective Friedel-Crafts Heteroarylation Reactions.

Cesium carbonate-mediated reaction of 2-hydroxybenzaldehydes and 2-bromoallyl sulfones afforded 2H- and 4H-chromenol derivatives endowed with a 3-arylsulfonyl group. 2-Bromoallyl sulfones functioned as synthetic equivalents of allenyl sulfones under these conditions. The 2H- and 4H-chromenol derivatives underwent regioselective Friedel-Crafts reactions with heteroarenes in the presence of p-toluenesulfonic acid to afford 4-heteroaryl-4H-chromene derivatives in excellent yields.

1,2-Benzoquinones in Diels-Alder reactions, dipolar cycloadditions, nucleophilic additions, multicomponent reactions and more.

A brief account of the recent developments in the chemistry of 1,2-benzoquinones is presented in this tutorial review. The title compounds exhibit commendable versatility in both Diels-Alder and dipolar cycloaddition reactions. They have also been employed as electrophilic reaction partners in nucleophile-triggered catalytic processes and related multicomponent reactions. These, along with other reactions described here, lead to the synthesis of densely functionalised carbocyclic and heterocyclic frameworks that are otherwise difficult to access.

Employing homoenolates generated by NHC catalysis in carbon-carbon bond-forming reactions: state of the art.

Homoenolate is a reactive intermediate that possesses an anionic or nucleophilic carbon ß to a carbonyl group or its synthetic equivalent. The recent discovery that homoenolates can be generated from α,ß-unsaturated aldehydes via N-Heterocyclic Carbene (NHC) catalysis has led to the development of a number of new reactions. A majority of such reactions include the use of carbon-based electrophiles, such as aldehydes, imines, enones, dienones etc. resulting in the formation of a variety of annulated as well as acyclic products. The easy availability of chiral NHCs has allowed the development of very efficient enantioselective variants of these reactions also. The tolerance showed by NHCs towards magnesium and titanium based Lewis acids has been exploited in the invention of cooperative catalytic processes. This tutorial review focuses on these and other types of homoenolate reactions reported recently, and in the process, updates the previous account published in 2008 in this journal.

Rapid synthesis of azepinoindole derivatives from tryptamine sulfonamides and bromoallyl sulfones via an acid-mediated cyclization and rearrangement.

The azepinoindole framework present in natural alkaloids such as subincanadine F, ibogaine and catharanthine was formed in a novel acid-promoted cyclization-rearrangement of tryptamine-derived N-sulfonyl enamines. The latter were conveniently prepared via a cesium carbonate mediated formal vinylic substitution reaction of 2-bromoallyl sulfones (allenyl sulfone surrogate) and tryptamine sulfonamides. The azepinoindole forming cyclization-rearrangement involves the initial generation of a six-membered tetrahydro-ß-carboline derivative. The steric bulk of the N-sulfonyl group on tryptamine plays an important role in deciding the reaction outcome.

Total syntheses of the furanosesquiterpenes crassifolone and dihydrocrassifolone via an Au(I)-catalysed intramolecular Michael addition reaction.

The racemic modifications of title natural products 1 and 2 have been synthesised for the first time. The key step was the Au(i)-catalysed conversion of the furanyl-substituted ynone 13 into the annulated furan 14.

The Au(I)-catalyzed intramolecular hydroarylation of terminal alkynes under mild conditions: application to the synthesis of 2H-chromenes, coumarins, benzofurans, and dihydroquinolines.

Operationally simple Au(I)-catalyzed intramolecular hydroarylation (IMHA) reactions of terminal alkynes that proceed in high yield and under very mild conditions are described. These processes involve low catalyst loadings, mild reaction temperatures, and short reaction times, require no cocatalysts or additives, and allow for the generation of a number of important heterocyclic motifs from readily accessible starting materials.

Oxygenative and Dehydrogenative [3 + 3] Benzannulation Reactions of α,ß-Unsaturated Aldehydes and γ-Phosphonyl Crotonates Mediated by Air: Regioselective Synthesis of 4-Hydroxybiaryl-2-carboxylates.

Regioselective synthesis of 4-hydroxybiphenyl-2-carboxylates via the base-mediated oxygenative [3 + 3] benzannulation reaction of α,ß-unsaturated aldehydes and γ-phosphonyl crotonates is reported. A hydroxyl group is installed in the final product on the originally phosphorus-bound carbon via a novel oxygenative and dehydrogenative transformation. The reaction proceeds rapidly in an open flask, uses atmospheric oxygen as an oxidant, and affords good yields of substituted biaryl phenols.

The facile synthesis of 1-benzoazepine derivatives via gold-catalyzed regioselective cycloisomerization reactions of N-(o-alkynylaryl)-N-vinyl sulfonamides.

Gold-catalyzed, regioselective cycloisomerization of N-(o-alkynylaryl)-N-vinyl sulfonamides afforded high yields of 2-sulfonylmethyl-1-benzoazepine derivatives. This 7-endo-dig selective cyclization proceeds via the incorporation of an exocyclic double bond by a labile 1-benzoazepine intermediate. The cyclization substrates were assembled in two steps from readily available materials using Sonogashira coupling and a Cs2CO3-mediated formal vinylic substitution.

Pyridine-catalyzed addition of diaryl-1,2-diones to dimethyl butynedioate leading to the formation of 1,2-diaroyl dimethyl maleates via an unprecedented rearrangement.

[reaction: see text] Pyridine catalyzes the reaction of 1,2-diaryl diones with dimethyl butynedioate to afford diaroyl maleates. This unprecedented rearrangement involves a unique benzoyl migration and proceeds with complete stereoselectivity.