00854nas a2200145 4500008004100000245007000041210006800111260000800179300001600187490000700203520034500210100002900555700002200584856010200606 2012 eng d00aArynes in transition-metal-free multicomponent coupling reactions0 aArynes in transitionmetalfree multicomponent coupling reactions cFEB a1520–15220 v513 a

Let's couple together! The multicomponent reactions involving arynes offer direct access to unusual heterocyclic scaffolds and 1,2-disubstituted arenes. This transition-metal-free, one-pot construction of molecular complexity is likely to play a pivotal role in various carbon–carbon and carbon–heteroatom bond-forming reactions.

1 aBhojgude, Sachin, Suresh1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/arynes-transition-metal-free-multicomponent-coupling-reactions01086nas a2200157 4500008004100000245010500041210006900146260000800215300001600223490000700239520048000246100002300726700002900749700002200778856012800800 2012 eng d00aEfficient diels-alder reaction of 1,2-benzoquinones with arynes and its utility in one-pot reactions0 aEfficient dielsalder reaction of 12benzoquinones with arynes and cDEC a6238–62410 v143 a

A new protocol for the efficient Diels–Alder reaction of 1,2-benzoquinones with arynes is reported. The aryne generated by the fluoride-induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates undergoes a facile Diels–Alder reaction with 1,2-benzoquinones, affording the dioxobenzobicyclooctadienes in moderate to excellent yields. In addition, this methodology has been applied to the one-pot synthesis of benzoquinoxalinobarrelene and naphthalene derivatives.

1 aKaicharla, Trinadh1 aBhojgude, Sachin, Suresh1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/efficient-diels-alder-reaction-12-benzoquinones-arynes-and-its-utility-one-pot-reactions01049nas 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-arynes01102nas a2200169 4500008004100000022001400041245008800055210006900143260007100212300001400283490000700297520043500304100002900739700002300768700002200791856011900813 2013 eng d a1523-706000aEmploying arynes in transition-metal-free monoarylation of aromatic tertiary amines0 aEmploying arynes in transitionmetalfree monoarylation of aromati a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcNOV a5452-54550 v153 a

The highly monoselective N-arylation of aromatic tertiary amines using a transition-metal-free approach using arynes has been developed. The reaction afforded functionalized diaryl amines in moderate to excellent yield. High levels of functional group compatibility especially with halogen containing substrates, dyes and donor-acceptor systems, and high yields of products are the notable features of the present reaction.

1 aBhojgude, Sachin, Suresh1 aKaicharla, Trinadh1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/employing-arynes-transition-metal-free-monoarylation-aromatic-tertiary-amines-001182nas a2200181 4500008004100000245011100041210006900152260000800221300001600229490000700245520049500252100002600747700002900773700002200802700002400824700002200848856013000870 2014 eng d00aDiels-alder reaction of tropones with arynes: synthesis of functionalized benzobicyclo[3.2.2]nonatrienones0 aDielsalder reaction of tropones with arynes synthesis of functio cAPR a4757–47620 v793 a

A new procedure for the mild, practical, and scalable Diels–Alder reaction of tropones with arynes is reported. Differently substituted tropones undergo selective [4 + 2] cycloaddition with arynes generated in situ by the fluoride-induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates, allowing the formation of functionalized benzobicyclo[3.2.2]nonatrienone derivatives in moderate to good yields. In addition, the photophysical properties of the cycloadducts are presented.

1 aThangaraj, Manikandan1 aBhojgude, Sachin, Suresh1 aBisht, Rajesh, H.1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/diels-alder-reaction-tropones-arynes-synthesis-functionalized-benzobicyclo322nonatrienones01159nas 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-001568nas a2200169 4500008004100000245009400041210006900135260000800204300001600212490000700228520094200235100002901177700002601206700002401232700002201256856012001278 2014 eng d00aTandem [4 + 2]/[2 + 2] cycloaddition reactions involving indene or benzofurans and arynes0 aTandem 4 22 2 cycloaddition reactions involving indene or benzof cJUN a3576–35790 v163 a

The reaction of arynes with indene/benzofurans has been developed. The arynes were generated from 2-(trimethylsilyl)aryl triflates by the fluoride-induced 1,2-elimination react with indene or various benzofurans proceeding via a cascade reaction involving the Diels–Alder reaction and a [2 + 2] cycloaddition reaction. The tandem process afforded functionalized dihydrobenzocyclobutaphenanthrenes in moderate to good yields. Moreover, the method has been utilized for the one-pot synthesis of benzo[b]fluoranthene.

1 aBhojgude, Sachin, Suresh1 aThangaraj, Manikandan1 aSuresh, Eringathodi1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/tandem-4-22-2-cycloaddition-reactions-involving-indene-or-benzofurans-and-arynes01251nas a2200181 4500008004100000022001400041245012300055210006900178260007100247300001400318490000700332520049300339100002900832700003000861700002400891700002200915856013200937 2015 eng d a1523-706000aThree-component coupling involving arynes, aromatic tertiary amines, and aldehydes via aryl-aryl amino group migration0 aThreecomponent coupling involving arynes aromatic tertiary amine a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcDEC a6270-62730 v173 a

The transition-Metal-free multicomponent coupling of arynes, aromatic tertiary amines, and aldehydes proceeding via the aryl to aryl amino group migration has been demonstrated. This protocol allows rapid access to ortho-functionalized tertiary amines in moderate to good yields. Moreover, activated ketones can also be used as the aldehyde Component in the present reaction. The similarity of the aryl-aryl tertiary amino group migration with the Smiles rearrangement is striking.

1 aBhojgude, Sachin, Suresh1 aBaviskar, Dnyaneshwar, R.1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/three-component-coupling-involving-arynes-aromatic-tertiary-amines-and-aldehydes-aryl-aryl-005205nas 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-and01459nas a2200205 4500008004100000022001400041245009900055210006900154260007200223300001000295490000600305520068100311100001400992700002901006700002301035700002601058700001801084700002201102856012901124 2016 eng d a2052-412900aEmploying carboxylic acids in aryne multicomponent coupling triggered by aziridines/azetidines0 aEmploying carboxylic acids in aryne multicomponent coupling trig aPO BOX 1-18, NANKANG, TAIPEI 115, TAIWANbCHINESE CHEMICAL SOCcNOV a71-760 v33 a

The transition-metal-free aryne multicomponent coupling (MCC) involving carboxylic acids initiated by aziridines/azetidines has been reported. The use of aziridines as nucleophiles afforded N-aryl beta-amino alcohol derivatives and the application of azetidines as nucleophilic triggers furnished N-aryl gamma-amino alcohol derivatives in moderate to good yields. These reactions proceed under mild conditions and result in the formation of a new carbon-nitrogen bond and a new carbon-oxygen bond. The utility of carboxylic acids in aryne MCCs has been demonstrated, and the synthetic potential of phenols as acid surrogates in the present aryne MCCs has been realized.

1 aRoy, Tony1 aBhojgude, Sachin, Suresh1 aKaicharla, Trinadh1 aThangaraj, Manikandan1 aGarai, Bikash1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/employing-carboxylic-acids-aryne-multicomponent-coupling-triggered-aziridinesazetidines-001175nas a2200181 4500008004100000022001400041245011300055210006900168260011000237300001400347490000700361520040400368100002600772700002900798700002000827700002200847856012400869 2016 eng d a1359-734500aFrom insertion to multicomponent coupling: temperature dependent reactions of arynes with aliphatic alcohols0 aFrom insertion to multicomponent coupling temperature dependent  aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcNOV a1665-16680 v523 a

The temperature dependent selectivity switch in the reaction of arynes with aliphatic alcohols in THF has been reported. At -20 degrees C, arynes smoothly insert into the O-H bond of alcohols to form alkyl aryl ethers. Interestingly, at 60 degrees C, a highly selective multicomponent coupling occurs with the solvent THF acting as the nucleophilic trigger affording (4-(alkoxy)butoxy)arenes.

1 aThangaraj, Manikandan1 aBhojgude, Sachin, Suresh1 aMane, Manoj, V.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/insertion-multicomponent-coupling-temperature-dependent-reactions-arynes-aliphatic-001313nas a2200181 4500008004100000245010100041210006900142260000800211300001400219490000700233520065000240100002600890700002900916700002200945700002400967700002200991856011801013 2016 eng d00aSelective synthesis of N-unsubstituted and N-arylindoles by the reaction of arynes with azirines0 aSelective synthesis of Nunsubstituted and Narylindoles by the re cSEP a8604-86110 v813 a

The transition-metal-free and temperature-dependent highly selective reaction of arynes with 2H-azirines allowing the synthesis of either N-unsubstituted or N-arylindoles has been developed. At 60 degrees C, arynes generated from 2-(trimethylsilyl)aryl triflates smoothly insert into 2H-azirines to form 2,3-diarylindoles with high selectivity. Interestingly, when the reaction was performed at -10 degrees C, the selectivity was switched to the formation of 1,2,3-triarylindoles in good yields.

1 aThangaraj, Manikandan1 aBhojgude, Sachin, Suresh1 aJain, Shailja", "1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/selective-synthesis-n-unsubstituted-and-n-arylindoles-reaction-arynes-azirines01711nas a2200169 4500008004100000245012800041210006900169260000800238300001600246490000700262520105300269100002901322700001401351700002401365700002201389856013001411 2016 eng d00aSubstrate-controlled selectivity switch in the three-component coupling involving arynes, aromatic tertiary amines, and CO20 aSubstratecontrolled selectivity switch in the threecomponent cou cOCT a5424–54270 v183 a

The transition-metal-free multicomponent coupling involving arynes, aromatic tertiary amines, and CO2 is reported. The reaction exhibits switchable selectivity depending on the electronic nature of the aromatic amines used. With amines bearing electron-releasing/neutral groups as the nucleophilic trigger, the reaction afforded 2-arylamino benzoates via a nitrogen to oxygen alkyl group migration. Employing electron-deficient amines in the reaction furnished 2-aminoaryl benzoates proceeding via the aryl to aryl amino group migration resembling a Smiles rearrangement.

1 aBhojgude, Sachin, Suresh1 aRoy, Tony1 aGonnade, Rajesh, G.1 aBiju, Akkattu, T. uhttps://library.ncl.res.in/content/substrate-controlled-selectivity-switch-three-component-coupling-involving-arynes-aromatic