Alkyne nickel-catalyzed reactions

The regiochemistry of Al-H addition to unsymmetrically substituted alkynes can be significantly altered by the presence of a catalyst. This was first shown by Eisch and Foxton in the nickel-catalyzed hydroalumination of several disubstituted acetylenes [26, 32]. For example, the product of the uncatalyzed reaction of 1-phenyl-propyne (75) with BujAlH was exclusively ds-[3-methylstyrene (76). Quenching the intermediate organoaluminum compounds with DjO revealed a regioselectivity of 82 18. In the nickel-catalyzed reaction, cis-P-methylstyrene was also the major product (66%), but it was accompanied by 22% of n-propylbenzene (78) and 6% of (E,E)-2,3-dimethyl-l,4-diphenyl-l,3-butadiene (77). The selectivity of Al-H addition was again studied by deuterolytic workup a ratio of 76a 76b = 56 44 was found in this case. Hydroalumination of other unsymmetrical alkynes also showed a decrease in the regioselectivity in the presence of a nickel catalyst (Scheme 2-22). 

Scheme 6/4.18. Nickel-catalyzed reaction of oxabenzonornadiene with alkynes.

Novel transition metal-mediated strategies were also well represented this past year. Takahashi and co-workers reported a s nickel-catalyzed reaction between azaziconacyclopentadienes (9) and alkynes to form pyridines (10) of varying substitution patterns <00JA4994>. This methodology, a formal cyclotrimerization, is also noteworthy since two different alkynes can be used. In similar fashion, Eaton reported an aqueous, cobalt(II) catalyzed cyclotrimerization between two identical acetylenes and one nitrile to afford substituted pyridines . 

Tamao and Ito have reported a nickel-catalyzed protocol for the cyclization/hydrosilylation of 1,7-diynes to form (Z)-silylated dialkylidene cyclohexane derivatives.For example, reaction of 1,7-octadiyne with triethoxysilane catalyzed by a mixture of Ni(acac)2 (lmol%) and DIBAL-H (2mol%) in benzene at 50°G for 6h gave the corresponding silylated dialkylidene cyclohexane in 70% yield as a single isomer (Table 1). The reaction of 1,7-octadiyne was also realized with mono- and dialkoxysilanes, trialkylsilanes, and dialkylaminosilanes (Table 1). Diynes that possessed an internal alkyne also underwent nickel-catalyzed reaction, albeit with diminished efficiency (Table 1), while 1,6- and 1,8-diynes failed to undergo nickel-catalyzed cyclization/hydrosilylation. 

Aldehydes constitute useful electrophilic partners in such nickel-catalyzed reactions because the condensation between alkynes, aldehydes and diorganozinc compounds can afford stereodefined cyclic or acyclic ally lie alcohols67-69, as illustrated by the stereoselective cyclization of 111 to the corresponding 3-hydroxypyrrolidine (equation 46). Allenes or 1,3-dienes instead of alkynes also lead to similar reactivity70. 

Pyran-2-ones are accessed in good yield by a nickel-catalyzed reaction of internal alkynes with carbon dioxide under solvent free conditions (Equation 263) <2005SL2141>. 

Nickel-catalyzed reaction of 1,2-dihydrotetramethyldisilane with various internal alkynes affords silole (silacyclopentadiene) derivatives 90 in good yields (Eq.46) [54]. 

All products from the nickel-catalyzed reaction of allylic systems with alkynes can be derived from two main intermediates. The course of the reaction is dependent on the solvent, however, by appropriate choice of the reaction conditions, good yields of cyclopentenones can be attained in some cases38-39. 

Ishikawa and coworkers have postulated that nickelasilacyclobutenes are in equilibrium with silapropadiene nickel complexes (59), and that this rearrangement explains the observed products of nickel-catalyzed reactions with alkynes, such as those shown in Scheme 15318"321. More recently, the nickelasilacyclobutene 62 has been observed by NMR321. 

These poor selectivities, relative to the nickel catalyzed reactions, are perhaps not surprising. The difference in electron density between the two sp carbons in an unactivated alkyne is obviously much smaller compared to the two sp carbons in an electron-deficient olefin. Thus, the Bj type intermediate (Scheme 15) with an unactivated alkyne does not have much preference over the corresponding Bj type intermediate. 

Before 1970, the reactions of aryl halides (ArX) with nucleophiles were restricted to electron-deficient aryl halides via S Ar mechanisms. The reactivity of aryl hahdes in S Ar reactions decreases in the order ArF>ArCl>ArBr ArI [1]. The range of reactive nucleophiles was narrow, and reactions of alkenes or alkynes were not known. The discovery in 1968 of oxidative additions of palladium(O) (Fitton [2a]) and then nickel(O) (Kochi [2b]) with aryl hahdes (ArI>ArBr>ArCl) that generate ArM XL (M=Pd, Ni) paved the way to new palladium- and nickel-catalyzed reactions of aryl hahdes with C-nucleophiles, leading to the formation of C—C bonds. Palladium- or nickel-catalyzed cross-couphng reactions are described herein, following the historical order of discovery. 

Nickel-catalyzed reaction of bicyclopropylidene and terminal alkyne 108 gave the seven-membered ring compound 109, which is formed by [3-I-2-I-2] annulation (Scheme 2.70) [123]. 

There is only one example where methyleneaziridines undergo a C-C bond cleavage reaction The nickel-catalyzed reaction of methyleneaziridine 119 and nona-2,7-diyne gave [3-1-2] annulation product 120 via ring expansion of a nickelacycle by P-carbon elimination (Scheme 2.77) [129]. Monoyne failed to show reactivity, suggesting the free alkyne unit on the diyne plays a crucial role. 

A nickel-catalyzed reaction using a chelating bisphosphine ligand converted terminal alkynes into vinyl bromides with the desired selectivity [184]... 

Ananikov VP, Orlov NV, Kabeshov MA, Beletskaya IP, Starikova ZA. Stereoselective synthesis of a new t)fpe of 1, 3-dienes by ligand-controlled carbon-carbon and carbon-heteroatom bond formation in nickel-catalyzed reaction of diaryldichalcogenides with alkynes. Organometallics 2008 27 4056 061. 

Nickel-catalyzed reactions of aldehydes with alkynes and MejZn afford the corresponding allylic alcohols in good yields [186,187]. The reaction can also proceed intramolecularly [188]. 

Hydrophosphorylation of alkynes via external attack of //-phosphonate to an (alkyne)metal complex is a possible pathway, although the possibility has been concluded to be less likely as far as the nickel-catalyzed reaction is concerned [12]. However, such a process appears to proceed in early transition metal carbonyl-catalyzed reactiOTis [19]. For instance, refluxing a mixture of phenylacetylene, HP(0)(0Et)2, and Mo(CO)fi (10 mol%) affords the franr-addition product... 

Later, a nickel-catalyzed cascade conversion of propargyl halides and propargyl alcohol into a pyrone in water was reported. The reaction involved a carbonylation by CO and a cyanation by KCN (Eq. 4.55).96 Recently, Gabriele et al. explored a facile synthesis of maleic acids by palladium catalyzed-oxidative carbonylation of terminal alkynes in aqueous DME (1,2-dimethoxyethane) (Eq. 4.56).97... 

A broad array of mechanistic pathways may be considered in the different variants of nickel-catalyzed reductive couplings of aldehydes and alkynes, and a generalized overview of possible mechanisms has been previously described [10]. Whereas a comprehensive mechanistic study has not been presented, a number of key observations have been illustrated that provide insight into how the nickel-catalyzed reductive couplings of aldehydes and alkynes proceed. It should be stressed at the outset that the different reaction variants may proceed by different mechanisms. 

Most studies on nickel-catalyzed domino reactions have been performed by Ikeda and colleagues [287], who observed that alkenyl nickel species, obtained from alkynes 6/4-41 and a (jr-allyl) nickel complex, can react with organometallics as 6/4-42. If this reaction is carried out in the presence of enones 6/4-43 and TM SCI, then coupling products such as 6/4-44 are obtained. After hydrolysis, substituted ketones 6/4-45 are obtained (Scheme 6/4.12). With cyclic and (5-substituted enones the use of pyridine is essential. Usually, the regioselectivity and stereoselectivity of the reactions is very high. On occasion, alkenes can be used instead of alkynes, though this is rather restricted as only norbornene gave reasonable results [288]. 

In the course of investigation into new C-C bond formation processes, Hiyama has developed an efficient nickel-catalyzed arylcyanation of alkynes.67 The addition reaction of an aryl-CN bond to alkyne affords aryl-substituted alkene nitrile in good yield. Good regioselectivity is reported in the case of unsymmetrical alkynes with two sterically different substituents. 

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]. 

The reaction of heterocyclic lithium derivatives with organic halides to form a C-C bond has been discussed in Section 3.3.3.8.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp2 carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable heterocyclic metal derivative. The metal is usually zinc, magnesium, boron or tin occasionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated heterocycles with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. 

Jamison has reported the unprecedented nickel-catalyzed assembly of allylic amines 156 from three simple starting materials alkynes, imines, and trialkylbor-anes or boronic acids. The participation of boronic acids in this methodology greatly enhances its synthetic potential, owing to their greater availability (Scheme 8.68) [145]. An asymmetric version of the reaction has also been developed but gave only moderate enantiomeric excesses (33 to 42%). 

Heterochalcogenides, with chromium, 5, 312 Heterocoupling reactions in olefin cross-metathesis, 11, 181 Pd-catalyzed, alkynes, 8, 274—275 Heterocubanes, reactions, 3, 8 Heterocumulenes in insertion reactions, 1, 107 nickel metallacycle reactions, 8, 103-104 Heterocyclic compounds... 

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