01049nas a2200169 4500008004100000245009600041210006900137260000800206300001600214490000700230520041600237100001700653700003300670700002900703700002200732856012500754 2012 eng d00aEfficient synthesis of gamma-keto sulfones by NHC-catalyzed intermolecular stetter reaction0 aEfficient synthesis of gammaketo sulfones by NHCcatalyzed interm cMAY a2830–28330 v143 a

The N-heterocyclic carbene-catalyzed intermolecular Stetter reaction of aldehydes with α,β-unsaturated sulfones allows the atom-economic and selective formation of γ-keto sulfones in good yields. Key to the success of this unique transition-metal-free carbon–carbon bond-forming reaction is the right choice of the NHC precursor and base. The reaction tolerates a broad range of different aldehydes.

1 aBhunia, Anup1 aYetra, Santhivardhana, Reddy1 aBhojgude, Sachin, Suresh1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/efficient-synthesis-gamma-keto-sulfones-nhc-catalyzed-intermolecular-stetter-reaction00974nas a2200169 4500008004100000245007600041210006900117260000800186300001600194490000700210520039300217100002900610700002300639700001700662700002200679856010300701 2012 eng d00aPractical and general diels-alder reaction of pentafulvenes with arynes0 aPractical and general dielsalder reaction of pentafulvenes with  cAUG a4098–41010 v143 a

A high-yielding, versatile and practical Diels–Alder reaction of pentafulvenes with arynes under mild reaction conditions is reported. The aryne generated by the fluoride induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates undergoes efficient cycloaddition with 6-substituted and 6,6-disubstituted pentafulvenes leading to the formation of benzonorbornadiene derivatives.

1 aBhojgude, Sachin, Suresh1 aKaicharla, Trinadh1 aBhunia, Anup1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/practical-and-general-diels-alder-reaction-pentafulvenes-arynes01722nas a2200169 4500008004100000022001400041245011700055210006900172260011000241300001400351490000700365520098000372100001701352700003301369700002201402856012801424 2012 eng d a0306-001200aRecent advances in transition-metal-free carbon-carbon and carbon-heteroatom bond-forming reactions using arynes0 aRecent advances in transitionmetalfree carboncarbon and carbonhe aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcJAN a3140-31520 v413 a

This tutorial review is aimed at highlighting recent developments in transition-metal-free carbon-carbon and carbon-heteroatom bond-forming reactions utilizing a versatile class of reactive intermediates, viz., arynes, which hold the potential for numerous applications in organic synthesis. Key to the success of the resurgence of interest in the rich chemistry of arynes is primarily the mild condition for their generation by the fluoride-induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates. Consequently, arynes have been employed for the construction of multisubstituted arenes with structural diversity and complexity. The versatile transition-metal-free applications of arynes include cycloaddition reactions, insertion reactions and multicomponent reactions. In addition, arynes have found applications in natural product synthesis. Herein, we present a concise account of the major developments that occurred in this field during the past eight years.

1 aBhunia, Anup1 aYetra, Santhivardhana, Reddy1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/recent-advances-transition-metal-free-carbon-carbon-and-carbon-heteroatom-bond-forming-001071nas a2200181 4500008004100000022001400041245007300055210006900128260007100197300001400268490000700282520040800289100001700697700002100714700002400735700002200759856010800781 2013 eng d a1523-706000aMulticomponent reactions involving arynes, quinolines, and aldehydes0 aMulticomponent reactions involving arynes quinolines and aldehyd a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcSEP a4620-46230 v153 a

The multicomponent reaction involving arynes, quinolines, and aldehydes leading to the diastereoselective synthesis of benzoxazino quinoline derivatives in good yields proceeding via 1,4-zwitterionic intermediates is reported. In addition, the synthetic potential of various carbonyl compounds in this reaction as well as the utility of isoquinoline as the nucleophilic trigger has been examined.

1 aBhunia, Anup1 aPorwal, Digvijay1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/multicomponent-reactions-involving-arynes-quinolines-and-aldehydes-001054nas a2200181 4500008004100000022001400041245011700055210006900172260007100241300001400312490000700326520032500333100001700658700001700675700002600692700002200718856013200740 2013 eng d a1523-706000aNHC-Catalyzed reaction of enals with hydroxy chalcones: diastereoselective synthesis of functionalized coumarins0 aNHCCatalyzed reaction of enals with hydroxy chalcones diastereos a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcAPR a1756-17590 v153 a

The N-heterocyclic carbene-catalyzed annulation of enals with 2'-hydroxy chalcones afford cyclopentane-fused coumarin derivatives with an excellent level of diastereocontrol. The reaction tolerates a broad range of functional groups; 25 examples are given, and a preliminary mechanistic investigation is provided.

1 aBhunia, Anup1 aPatra, Atanu1 aPuranik, Vedavati, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/nhc-catalyzed-reaction-enals-hydroxy-chalcones-diastereoselective-synthesis-functionalized-001000nas a2200181 4500008004100000245009700041210006900138260000800207300001800215490000700233520033900240100001700579700001400596700002100610700003500631700002200666856013000688 2013 eng d00aTransition-metal-free multicomponent reactions involving arynes, N-heterocycles, and isatins0 aTransitionmetalfree multicomponent reactions involving arynes Nh cAUG a10040–100430 v523 a

Mix and match: With isoquinoline as the nucleophilic trigger, multicomponent reactions afforded spirooxazino isoquinoline derivatives, proceeding through 1,4-dipolar intermediates. The use of pyridine as a nucleophile furnished indolin-2-one derivatives, with the reaction likely proceeding through a pyridylidene intermediate.

1 aBhunia, Anup1 aRoy, Tony1 aPachfule, Pradip1 aRajamohanan, Pattuparambil, R.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/transition-metal-free-multicomponent-reactions-involving-arynes-n-heterocycles-and-isatins01159nas a2200181 4500008004100000022001400041245010600055210006900161260007100230300001200301490000700313520043900320100002900759700001700788700002400805700002200829856012600851 2014 eng d a1523-706000aEfficient synthesis of 9-aryldihydrophenanthrenes by a cascade reaction involving arynes and styrenes0 aEfficient synthesis of 9aryldihydrophenanthrenes by a cascade re a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcFEB a676-6790 v163 a

A mild, general, and transition-metal-free protocol for the synthesis of 9,10-dihydrophenanthrenes is reported. The aryne generated by the fluoride-induced,1,2-elimination of 2-(trimethylsilyl)aryl triflates undergoes an efficient cascade reaction initiated by the Diels-Alder reaction with the differently substituted styrenes leading to the formation of 9-aryl-9,10-dihydrophenanthrene derivatives in moderate to good yields.

1 aBhojgude, Sachin, Suresh1 aBhunia, Anup1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/efficient-synthesis-9-aryldihydrophenanthrenes-cascade-reaction-involving-arynes-and-001218nas a2200157 4500008004100000245009700041210006900138260000800207300001200215490000700227520058500234653007400819100001700893700002200910856012800932 2014 eng d00aEmploying arynes in transition-metal-free, N-heterocycles initiated multicomponent reactions0 aEmploying arynes in transitionmetalfree Nheterocycles initiated  cJAN a608-6140 v253 a

Transition-metal-free multicomponent reactions involving arynes, N-heterocycles, and various carbonyl compounds have been reported. With (iso)quinoline as the nucleophile and carbonyl compounds, such as aldehydes, ketones, and N-substituted isatins as electrophiles, the reaction afforded oxazino (iso)quinoline derivatives and the reaction proceeded via 1,4-dipolar intermediates. Interestingly, when the nucleophilic trigger used is pyridine, the reaction furnished indolin-2-one derivatives, and it is probable that the reaction proceeds via a pyridylidene intermediate.

10aarynes - multicomponent reaction - oxindoles - pyridines - quinolines1 aBhunia, Anup1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/employing-arynes-transition-metal-free-n-heterocycles-initiated-multicomponent-reactions01060nas a2200169 4500008004100000022001400041245010800055210006900163260007100232300001400303490000700317520037900324100001700703700001700720700002200737856013100759 2014 eng d a1523-706000aFacile synthesis of gamma-ketophosphonates by an intermolecular stetter reaction onto vinylphosphonates0 aFacile synthesis of gammaketophosphonates by an intermolecular s a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcSEP a4798-48010 v163 a

The atom-economic and practical N-heterocyclic carbene (NHC) catalyzed Stetter reaction for the synthesis of gamma-ketophosphonates by the reaction of aromatic aldehydes with vinylphosphonates is reported. The NHC derived from N-mesitylimidazolium salt (IMes) was an effective catalyst for this transformation, and the products were formed in moderate to good yields.

1 aPatra, Atanu1 aBhunia, Anup1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/facile-synthesis-gamma-ketophosphonates-intermolecular-stetter-reaction-vinylphosphonates-001426nas a2200193 4500008004100000022001400041245007200055210006900127260011000196300001600306490000700322520068800329100001701017700002301034700002101057700002401078700002201102856010801124 2014 eng d a1359-734500aMulticomponent reactions involving phosphines, arynes and aldehydes0 aMulticomponent reactions involving phosphines arynes and aldehyd aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcAUG a11389-113920 v503 a

Although nucleophilic phosphine-catalysis is a powerful tool for the construction of various carbocycles and heterocycles, the reactions in which phosphines are incorporated into the final product are rare, and the reports on phosphine addition to highly electrophilic arynes are scarce. Herein, we report the phosphine triggered multicomponent reaction of arynes and aldehydes, which takes place via the formal [3+2] cycloaddition of an initially generated 1,3-phosphonium zwitterion from phosphines and arynes with aldehydes. The reaction resulted in the formation of a diverse range of stable pentacovalent phosphoranes in good yields based on the benzooxaphosphole system.

1 aBhunia, Anup1 aKaicharla, Trinadh1 aPorwal, Digvijay1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/multicomponent-reactions-involving-phosphines-arynes-and-aldehydes-001282nas a2200181 4500008004100000022001400041245014600055210006900201260007100270300001400341490000700355520053800362100001700900700001400917700002400931700002200955856012300977 2014 eng d a1523-706000aRapid access to benzoxaphospholes and their spiro analogues by a three-component coupling involving arynes, phosphines, and activated ketones0 aRapid access to benzoxaphospholes and their spiro analogues by a a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcOCT a5132-51350 v163 a

An operationally simple multicomponent coupling involving in situ generated arynes from 2 (trimethylsilyl)aryl triflates, phosphines, and various acyclic and cyclic activated carbonyl compounds has been developed. The reaction proceeds via a formal [3 + 2] cycloaddition mode giving access to differently substituted (spiro)benzoxaphosphole derivatives in moderate to good yields Mild reaction conditions. a broad scope. and the possibility of varying all the three-components are the notable features of the present reaction.

1 aBhunia, Anup1 aRoy, Tony1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/rapid-access-benzoxaphospholes-and-their-spiro-analogues-three-component-coupling-001083nas a2200181 4500008004100000245013300041210006900174260000800243300001600251490000700267520038900274100003300663700001400696700001700710700002100727700002200748856013100770 2014 eng d00aSynthesis of functionalized coumarins and quinolinones by NHC-catalyzed annulation of modified enals with heterocyclic C-H acids0 aSynthesis of functionalized coumarins and quinolinones by NHCcat cAPR a4245–42510 v793 a

N-Heterocyclic carbene (NHC) catalyzed lactonization and lactamization of 2-bromoenals with heterocyclic C–H acids proceeding via the α,β-unsaturated acyl azolium intermediates is reported. The reaction furnished coumarin- or quinolinone-fused lactone/lactam derivatives. In addition, results of the enantioselective version of this reaction using chiral NHC are presented.

1 aYetra, Santhivardhana, Reddy1 aRoy, Tony1 aBhunia, Anup1 aPorwal, Digvijay1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/synthesis-functionalized-coumarins-and-quinolinones-nhc-catalyzed-annulation-modified-enals01411nas a2200181 4500008004100000245014900041210006900190260000800259300001400267490000600281520070200287100001700989700001701006700003301023700002401056700002201080856012701102 2015 eng d00aDiastereoselective synthesis of cyclopentanone-fused spirooxindoles by N-heterocyclic carbene-catalyzed homoenolate annulation with isatilidenes0 aDiastereoselective synthesis of cyclopentanonefused spirooxindol cSEP a1584-15880 v23 a

N-Heterocyclic carbene (NHC)-catalyzed formal [3 + 2] annulation of α,β-unsaturated aldehydes with N-substituted isatilidenes resulting in the diastereoselective synthesis of cyclopentanone-fused spirooxindoles is demonstrated. Mechanistically, the reaction proceeds via the generation of homoenolate equivalent intermediates from NHC and enals, which on interception with isatilidenes afford spiroheterocyclic compounds bearing an all-carbon quaternary spiro-center in moderate to good yields and generally with high diastereoselectivity. Moreover, the functionalization of the spirooxindoles as well as the initial studies on the enantioselective version of this reaction are presented.

1 aPatra, Atanu1 aBhunia, Anup1 aYetra, Santhivardhana, Reddy1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/diastereoselective-synthesis-cyclopentanone-fused-spirooxindoles-n-heterocyclic-carbene01042nas a2200169 4500008004100000245013400041210006900175260000800244300001600252490000700268520038100275100001700656700002500673700002400698700002200722856012800744 2015 eng d00aReaction of N-heterocyclic carbenes with chalcones leading to the synthesis of deoxy-breslow intermediates in their oxidized form0 aReaction of Nheterocyclic carbenes with chalcones leading to the cJUL a13690-136930 v513 a

The synthesis of deoxy-Breslow intermediates in their oxidized form has been developed via the reaction of N-heterocyclic carbenes (NHCs) with chalcones. Moreover, the initial tetrahedral adduct formed from the 1,4-addition of NHCs to chalcones is also isolated.

 
1 aBhunia, Anup1 aThorat, Shridhar, H.1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/reaction-n-heterocyclic-carbenes-chalcones-leading-synthesis-deoxy-breslow-intermediates05205nas a2200181 4500008004100000245012200041210007100163260000800234300001400242490000700256520442000263653003504683653009704718100002904815700001704844700002204861856014004883 2016 eng d00aEmploying arynes in diels–alder reactions and transition-metal-free multicomponent coupling and arylation reactions0 aEmploying arynes in diels–alder reactions and transitionmetalfre cSEP a1658-16700 v493 a

Conspectus

Arynes are highly reactive intermediates having several applications in organic synthesis for the construction of various ortho-disubstituted arenes. Traditionally, arynes are generated in solution from haloarenes under strongly basic conditions. However, the scopes of many of the aryne reactions are limited because of the harsh conditions used for their generation. The renaissance of interest in aryne chemistry is mainly due to the mild conditions for their generation by the fluoride-induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates. This Account is focused on the Diels–Alder reaction of arynes and their transition-metal-free application in multicomponent couplings as well as arylation reactions.

The Diels–Alder reaction of arynes is a powerful tool for constructing benzo-fused carbocycles and heterocycles. In 2012, we developed an efficient, broad-scope, and scalable Diels–Alder reaction of pentafulvenes with arynes affording benzonorbornadiene derivatives. Subsequently, we accomplished the Diels–Alder reaction of arynes with dienes such as 1,2-benzoquinones and tropones. Moreover, we uncovered a transition-metal-free protocol for the synthesis of 9,10-dihydrophenanthrenes by the reaction of arynes with styrenes that proceeds via a Diels–Alder/ene-reaction cascade. In addition, we demonstrated the reaction of arynes with indene/benzofurans, which proceeds via a tandem [4 + 2]/[2 + 2] sequence.

Multicomponent coupling (MCC) involving arynes mainly comprises the initial addition of a nucleophile to the aryne followed by interception of the aryl anion intermediate with an electrophile (provided the nucleophilic and electrophilic moieties do not belong to the same molecule). We have disclosed aryne MCCs initiated by N-heterocycles such as (iso)quinoline, pyridine, and aziridines. When (iso)quinoline is used as the nucleophilic trigger and N-substituted isatin as the third component, the reaction affords spirooxazino(iso)quinolines via 1,4-dipolar intermediates. Unexpectedly, using pyridine affords indolin-2-ones, where the reaction proceeds via the pyridylidene intermediate. Additionally, we developed the phosphine-triggered aryne MCCs for the synthesis of functionalized benzooxaphospholes. In another phase of our work, we studied the synthetic utility of CO2 as a one-carbon synthon in aryne MCCs for the synthesis of phthalimides.

Engaging arynes as an aryl source is one of the transition-metal-free methods for arylation reactions. We have demonstrated the N-arylation of aromatic tertiary amines and O-arylation of aliphatic alcohols using arynes.

It is anticipated that the chemistry of arynes will continue to prosper and will lead to surprising developments for the synthesis of various 1,2-disubstituted arenes of molecular complexity and structural diversity. Future challenges in this area include the utility of arynes in enantioselective transformations and the synthesis and reactions of exotic heterocyclic arynes.

10a2-Benzoquinones; Cycloaddition10aFacile N-arylation; O-arylation; One-Pot; Aldehydes; Benzyne; Amines; Heterocycles; Acids; 11 aBhojgude, Sachin, Suresh1 aBhunia, Anup1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/employing-arynes-diels%E2%80%93alder-reactions-and-transition-metal-free-multicomponent-coupling-and01600nas a2200169 4500008004100000245010900041210006900150260000800219300001400227490000700241520094600248100001701194700003301211700002401244700002201268856014001290 2016 eng d00aSynthesis of 4H-chromenes by an unexpected, K3PO4-mediated intramolecular rauhut–currier type reaction0 aSynthesis of 4Hchromenes by an unexpected K3PO4mediated intramol cAPR a5612-56160 v143 a

In an attempt to develop the umpolung of Michael acceptors using chalcones having an enoate moiety under N-heterocyclic carbene (NHC) catalysis, a K3PO4-mediated intramolecular Rauhut–Currier type reaction was observed. This C(sp2)–C(sp2) coupling reaction afforded the biologically important 4H-chromenes in moderate to good yields. It is likely that the enol ether functionality acts as the nucleophilic trigger in this reaction.

1 aBhunia, Anup1 aYetra, Santhivardhana, Reddy1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/synthesis-4h-chromenes-unexpected-k3po4-mediated-intramolecular-rauhut%E2%80%93currier-type-reaction01711nas a2200193 4500008004100000245015800041210007000199260000800269300001600277490000700293520094900300100002301249700001701272700001701289700003101306700002701337700002201364856013101386 2017 eng d00aEnantioselective synthesis of spiro γ-butyrolactones by N-heterocyclic carbene (NHC)-catalyzed formal [3+2] annulation of enals with 3-hydroxy oxindoles0 aEnantioselective synthesis of spiro γbutyrolactones by Nheterocy cFEB a2013 - 20190 v163 aThe N-heterocyclic carbene (NHC)-catalyzed enantioselective formal [3 + 2] annulation of α,β-unsaturated aldehydes with 3-hydroxy oxindoles is presented. Under oxidative conditions using the bisquinone oxidant, the reaction resulted in the synthesis of spiro γ-butyrolactones in moderate to good yields, enantioselectivity and diastereoselectivity. The reaction likely proceeds via the generation of the NHC-bound α,β-unsaturated acylazolium intermediate from enals, which was intercepted by the dioxindoles in a formal [3 + 2] pathway to form the spirocyclic compounds. However, a deeper mechanistic investigation revealed that the reaction can also proceed via the homoenolate intermediate. In this case, the dioxindole was oxidized to the corresponding isatin derivative using traces of air under basic conditions, and was intercepted with the NHC-bound homoenolate intermediate in a formal [3 + 2] pathway to afford the spiro compound.1 aMukherjee, Subrata1 aJoseph, Sumi1 aBhunia, Anup1 aGonnade, Rajesh, Ghanshyam1 aReddy, Santhi, Vardhan1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/enantioselective-synthesis-spiro-%CE%B3-butyrolactones-n-heterocyclic-carbene-nhc-catalyzed01111nas a2200157 4500008004100000245010500041210006900146260000800215300001600223490000700239520052200246100002200768700001700790700002200807856012400829 2018 eng d00aEmploying arynes for the generation of aryl anion equivalents and subsequent reaction with aldehydes0 aEmploying arynes for the generation of aryl anion equivalents an cSEP a11333-113400 v833 a

Arynes are highly reactive intermediates, which are utilized for the electrophilic arylation of various X-H bonds (X = O, N, S etc.). Herein, a new synthetic strategy is demonstrated, where arynes are converted into aryl anion equivalents by treatment with phosphines and a base. The addition of phosphines to arynes form the phosphonium salts, which in the presence of a carbonate base generates the aryl anion equivalent. Subsequent addition of the aryl anions with aldehydes afforded the secondary alcohols.

1 aGaykar, Rahul, N.1 aBhunia, Anup1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/employing-arynes-generation-aryl-anion-equivalents-and-subsequent-reaction-aldehydes