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-reaction01159nas 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-reactions05205nas 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-and01711nas 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