Alkyne insertion, nickel

The reaction of alkenylcarbene complexes and alkynes in the presence of Ni(0) leads to cycloheptatriene derivatives in a process which can be considered as a [3C+2S+2S] cycloaddition reaction [125]. As shown in Scheme 77, two molecules of the alkyne and one molecule of the carbene complex are involved in the formation of the cycloheptatriene. This reaction is supposed to proceed through the initial formation of a nickel alkenylcarbene complex. A subsequent double regioselective alkyne insertion produces a new nickel carbene complex, which evolves by an intramolecular cycloprop anation reaction to form a nor-caradiene intermediate. These species easily isomerise to the observed cycloheptatriene derivatives (Scheme 77). 

Ishikawa and coworkers have studied the unique reactivity of strained cyclic disilanes (Equation 9.11) [35]. Transition metals, especially those of Group 10, readily insert into the Si—Si bond of disilacyclobutene 118 and can catalyze the addition of that bond across a variety of unsaturated acceptors. In the case of Ni(0)-catalyzed reactions of 118 with trimethylsilyl alkynes, insertion was found to occur both in a 1,2-and in a 1,1-fashion. The latter of these pathways implies a 1,2-silyl-migration, presumably occurring at the metal center. A nickel vinylidene intermediate was therefore proposed, though efforts to prove its existence were inconclusive. Similar vinylidene intermediates have been proposed by Ishikawa and coworkers to account for migrations observed in related palladium- and platinum-catalyzed reactions [36]. 

A wide range of substituted isoquinolines (93) have been synthesized via a highly efficient nickel-catalysed annulation of the r-butylimines of 2-iodobenzaldehydes (91) and various alkynes (92) examination of the regiochemistry of the reaction revealed the operation of two different alkyne insertion pathways.119... 

A nickel-catalysed alkyne insertion between the carbonyl carbon and the -carbon of the cyclobutanone was achieved by combining a ketone-alkyne coupling reaction with a /3-carbon elimination process (Scheme 79).121 The reaction uses cyclobutanones as a four-carbon unit and provides access to substituted cyclohexenones. 

Vinyl sulfides have been prepared by the catalytic addition of the S—H bond of thiols (85) to terminal alkynes (86) under solvent-free conditions using the nickel complex Ni(acac)2 (47). High alkyne conversions (up to 99%) were achieved after 30 min at 40 °C in favor of the corresponding Markovnikov products (87) (equation 23). Other metal acetylacetonate complexes were examined for this reaction, but none showed any improvement over the nickel catalyst. Mechanistic details suggest that alkyne insertion into the Ni—S bond is important to the catalytic cycle and that nanosized structural units comprised of [Ni(SAr)2] represent the active form of the catalyst. Isothiocyanates and vinyl sulfides have been produced in related Rh(acac)(H2C=CH2)2 (6) and VO(acac)2 (35) catalyzed sulfenylation reactions of aryl cyanides and aryl acetylenes, respectively. 

The nickel-catalyzed carbonylation of allyl halides in the presence of alkynes and water produces 2,5-dienoic acids in good yields under very mild conditions (equation 25). This remarkable four-component reaction probably involves oxidative addition of the allyl chloride to the catalyst, followed by successive insertions of alkyne and CO, and finally hydrolysis. The carbon-carbon double bond derived from alkyne insertion is thus conjugated with the carbonyl group and generally has the (Z)-configuration. 

A number of transition-metal-mediated reactions involving addition of an alkyne to an organosilicon compound may involve an alkyne insertion step (Section III.A and Section VI.E.4). One example, for which alternative mechanisms are possible, is shown in equation 80224. Nickel silyl derivatives (bipy)Ni(SiX3)2 (SiX3 = SiCl3, SiMeCl2) react with... 

Recent studies on the allylation of alkynes with bis (7r-allyl) nickel have revealed that the Ni(0) generated in this process causes the trimeri-zation and, more importantly, the reductive dimerization of a portion of the alkyne (8). A deuterolytic work-up led to the terminally di-deuter-ated diene (5), supporting the presence of a nickelole precursor (4) (Scheme 1). The further interaction of 4 with 1, either in a Diels-Alder fashion (6) or by alkyne insertion in a C-Ni bond (7), could lead to the cyclic trimer 8 after extrusion of Ni(0), thereby accounting for the trimerizing action of Ni(0) on alkynes. This detection of dimer 5 then provided impetus for the synthesis of the unknown nickelole system to learn if its properties would accord with this proposed reaction scheme. Therefore, E,E-l,4-dilithio-l,2,3,4-tetraphenyl-l,3-butadiene (9) was treated with bis (triphenylphosphine) nickel (II) chloride or l,2-bis(di-phenylphosphino ethane)nickel(II) chloride to form the nickelole 10 (9) (Scheme 2). The nickelole reacted with dimethyl acetylenedicarboxylate to yield 11 and with CO to produce 12. Finally, in keeping with the hypothesis offered in Scheme 1, 10a did act as a trimerizing catalyst toward diphenylacetylene (13) to yield 14. 

Many examples of alkene and alkyne insertion into metal-carbon bonds can also be found in the section on homogeneous catalysis. Other recent examples include the insertion of conjugated dienes into palladium-allyl bonds, olefin arylation in the presence of palladium acetate, and the reaction of ethylene with arylmagnesium halides in the presence of nickel chloride. Reaction of isocyanates with nickel-ethynyl compounds... 

Other classes of nickel-catalyzed [3+2] cycloadditions include the addition of 2-haloacetophenone derivatives to alkynes to produce indenol derivatives (Scheme 3-36). This process likely involves initial oxidative addition to the haloaromatic, followed by alkyne insertion and carbonyl addition. In this case, zinc powder serves as reducing agent to regenerate the active nickel(0) catalyst. A mechanistically intriguing cycloaddition that proceeds without the action of reducing agents is the direct formation of bicyclic products from the addition of unsaturated ketones with alkynes. This process likely involves initial metallacycle formation followed by unusual rearrangement steps unique to the requisite doubly unsaturated carbonyl component. 

A theoretical investigation of the phenylcyanation of alkynes found that the mechanism involves rate-determining oxidative addition of nickel(O) to the Ph-CN bond, followed by alkyne insertion into the Ph-Ni bond then reductive elimination of the alkenyl-CN bond (Scheme 3-102). ... 

Alkyne Insertions with Nickel-Allyl Complexes... 

Matsubara and coworkers have recently developed a nickel-catalyzed cycloaddition of isatoic anhydrides with alkynes to afford 2,3-disubstituted indoles in good yields (Scheme 22.16). The cycloaddition reaction proceeds via a decarbonylation, decarboxylation, and alkyne insertion sequence [24]. 

The reaction mechanism is proposed after the isolation and structural confirmation of the activated alkene insertion species nickelacyclopentanes 6a from the reaction of nickel-carboryne with 2-vinylpyridine (Scheme 7.5). The sequential insertion of alkene and alkyne with excellent regioselectivity control by electronic effect results in the formation of 5. Alkyne inserts regioselectively into the Ni-Caikyi bond of the nickelacyclopentane, whereas the Ni-Cgage bond remains intact. Reductive elimination yields the final products 5. In fact, treatment of 6a with 3-hexyne affords the expected dihydrobenzocarborane... 

As in the case of carbonylation, the reaction of alkynes with nickel metallacycles is often followed by reductive elimination. In some cases, the insertion product is stable and can be isolated (e.g., alkyne insertion in nickelalac-tones or fluorinated metallacycles, Equation (99)), but more frequently it is unstable and decomposes rapidly to afford substituted benzenes, dihydronaphthalenes,naphthalenes, or phenanthrenes. " The reaction of Ni(0) dippe complexes with biphenylene and alkynes in the presence of traces of O2 catalytically produces phenanthrenes, in a process that involves the intermediacy of a carbonickelacycle. " ... 

Alkyne insertion was achieved using a nickel(0) catalyst [59]. The cyclobutenone-alkyne coupling reaction provided substituted phenols (Scheme 3.50). Unhke the thermal reaction, unactivated alkynes readily participated in aimulation. Regioselectivity of alkyne insertion was low. 

In 2009, Miura et al. reported an elegant assembly of pyrroles 38 from alkynes and A-sulfonyl-1,2,3-triazoles 36 (Scheme 12.16) [18,19]. The reaction proceeded at 100 °C in the presence of a nickel catalyst and aluminum co-catalyst to afford substituted pyrroles 38. It is worth mentioning that the starting material 36 can be produced readily by the copper-catalyzed azide-alkyne Huisgen cycloaddition. The reaction is thought to be initiated by tautomerization of the triazole to an a-iminodiazo compound, which reacts with Ni(0) to give a nickel carbenoid and then the azanickelacycle 37. Subsequent alkyne insertion to the azanickelacycle and reductive elimination lead to the formation of 38. 

Azanickelacycle formation with partial replacement of the heterocyclic moiety substance by the nickel catalyst was also employed for the synthesis of indoles, an important class of heterocycles found in natural products and pharmaceuticals. Maizum et al. demonstrated a nickel-catalyzed decarbonylative cycloaddition by which anthranilic acid derivatives 39, which are readily available, react with alkynes to afford substituted indoles 41 (Scheme 12.17) [20]. The reaction is supposed to proceed via oxidative addition and decarbonylation to afford azanickelacycle 40, followed by alkyne insertion, 1,3-acyl migration, and reductive elimination, to afford A-pivaloyl-protected indole 41. Deprotected indole 42 was obtained as the final product upon workup, that is, treatment of the reaction crude reaction mixture with NaSMe in MeOH. 

Inexpensive and easily available nickel acetylacetonate (Ni(acac)2) is employed as the catalyst precursor. The procedure can be easily scaled-up to prepare up to 50 g of the vinyl sulfides with high regioselectivity. Moreover, solvent-free conditions without chromatographical purification attain eco-friendly synthetic method of vinyl sulfides. The mechanistic study indicates that the catalytic hydrothiolation takes place under heterogeneous conditions with alkyne insertion into the Ni-S bond of nanosized nickel sulfide species. 

Two catalytic cycles are proposed to explain the difference in selectivity. In both cases, catalytic cycle is initiated by the oxidative addition of an alkynylstannane to nickel(O) species, leading to the formation of alkynylnickel(ll) complex 77 (Scheme 24).92 Then, an allene is inserted into the nickel(ll) complex in a manner which avoids steric repulsion with the butyl group to afford the anti-ir-a y complex 80. The carbometallation of the terminal alkyne can take place at the non-substituted allylic carbon of the corresponding syn-Ti-a y complex 78. The stereoselectivity is determined by the relative rate of the two possible insertion modes which depend on the ligand used. A bidentate... 

Nickel(O) catalysis has been utilized for a three-component coupling between an allylic electrophile, and alkyne, and AlMe3 or ZnMe2. This reaction takes place though the insertion of a 7r-nickel(ll) intermediate into the alkyne,... 

A nickel(O) complex catalyzes insertion of alkynes into cyclobutanones (Equation (79)).437 Formation of metalla-cycle 194 via oxidative cyclization of an alkyne with the carbonyl group of a cyclobutanone followed by /3-carbon elimination (formation of metallacycle 195) and reductive elimination are postulated for the mechanism (Scheme 92). 

Generally, cyclohexyne is an unstable molecule because of its ring strain. However, it can be stabilized by coordination to transition metals.35 The reduction of 1,2-dibromocyclohexene by sodium/mercury in the presence of a nickel-bromide complex afforded the Ni-alkyne complex 66 as a thermally stable and isolable compound (Scheme 22).36 Complex 66 smoothly reacted with C02 under atmospheric pressure to give nickelacycle 67 in good yield. Dimethyl acetylenedicarboxylate was inserted into the vinyl-nickel bond in 67 to give the seven-membered oxanickelacycle 68. 

Vinyl Fischer carbenes can be used as three-carbon components in Ni(0)-mediated and Rh(l)-catalyzed [3 + 2 + 21-reactions with alkynes (Schemes 48 and 49)142 and with allenes (Schemes 50 and 51).143 All three of the proposed mechanisms for the [3 + 2 + 2]-cycloadditions involve an initial carbene transfer from chromium to nickel or rhodium (Schemes 49, 52, and 53). As is seen from the products of the two [3 + 2 + 2]-reactions with 1,1-dimethylallene, although the nickel and rhodium carbenes 147G and 147K appear similar, the initial insertion of the allene occurs with opposite regioselectivity. 

The aforementioned dienyl dicopper derivatives show the characteristic reactivity of orga-nocopper compounds. However, one limitation to the use of copper is that an electron-withdrawing group is usually required for reaction with alkynes. In order to develop an insertion protocol for alkynes bearing electron-donating groups, transmetalation of zirco-nacyclopentadienes to nickel was investigated. 

Tamao and Ito proposed a mechanism for the nickel-catalyzed cyclization/hydrosilylation of 1,7-diynes initiated by oxidative addition of the silane to an Ni(0) species to form an Ni(ii) silyl hydride complex. Gomplexation of the diyne could then form the nickel(ii) diyne complex la (Scheme 1). Silylmetallation of the less-substituted G=C bond of la, followed by intramolecular / -migratory insertion of the coordinated G=G bond into the Ni-G bond of alkenyl alkyne intermediate Ila, could form dienylnickel hydride intermediate Ilia. Sequential G-H reductive elimination and Si-H oxidative addition would release the silylated dialkylidene cyclohexane and regenerate the silylnickel hydride catalyst (Scheme 1). 

Cyclotetramerization to form cyclooctatetraene occurs only with nickel.46,63 68 The best catalysts are octahedral Ni(II) complexes, such as bis(cyclooctatetraene) dinickel.46 Internal alkynes do not form cyclooctatetraene derivatives but participate in cooligomerization with acetylene. Of the possible mechanistic pathways, results with [l-13C]-acetylene81 favor a stepwise insertion process or a concerted reaction, and exclude any symmetric intermediate (cyclobutadiene, benzene). The involvement of dinuclear species are in agreement with most observations.46,82-84... 

The oxanickelacyclopentenone (41), formed from 2-butyne, COz, and nickel(O), was found to undergo reaction with activated alkynes by insertion to provide oxanickelacycloheptadienones (42) [Eq. (48)] (118). These novel... 

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