Cocyclization alkynes

The insensitivity of the cpCo core even allows elemental sulfur to be incorporated in the alkyne cocyclizations, and a series of cpCo-dithiolatoethene complexes have been obtained using a simple one-pot procedure (82UP1 83MI1) [Eq.(40)] (Table VII). 

Cocyclizations of internal alkynes and carbene complexes 57 with larger substituents R1 (e.g., R z Pr) not only lead to formation of an increased proportion of the regioisomers 60b, but also to that of the isomeric cyclopentadi-enes 61, which would result from 60a by 1,2-migration of the dimethylamino... 

The novel highly substituted spiro[4.4]nonatrienes 98 and 99 are produced by a [3+2+2+2] cocyclization with participation of three alkyne molecules and the (2 -dimethylamino-2 -trimethylsilyl)ethenylcarbene complex 96 (Scheme 20). This transformation is the first one ever observed involving threefold insertion of an alkyne and was first reported in 1999 by de Meijere et al. [81]. The structure of the product was eventually determined by X-ray crystal structure analysis of the quaternary ammonium iodide prepared from the regioisomer 98 (Ar=Ph) with methyl iodide. Interestingly, these formal [3+2+2+2] cycloaddition products are formed only from terminal arylacetylenes. In a control experiment with the complex 96 13C-labeled at the carbene carbon, the 13C label was found only at the spiro carbon atom of the products 98 and 99 [42]. 

Scheme 27 Cocyclization of the 1-naphthylcarbene complex 128 with ferf-butylphospha-alkyne 129 [91]...

Scheme 31 Formation of cyclopentenones 143 and 144 by a formal [4+2+1-2] cocyclization from the cyclopropylmethoxycarbenechromium complex 142 and alkynes [100-103]...

The reaction mechanism was considered to be oxidative cyclization, and pal-ladacyclopentene 32 was formed. Reductive elimination then occurs to give cyclobutene 33, whose bond isomerization occurs to give diene 28. The insertion of alkyne (DMAD) into the carbon palladium bond of 32 followed by reductive elimination occurs to give [2+2+2] cocyclization product 27. Although the results of the reactions of E- and Z-isomers of 29 with palladium catalyst 26a were accommodated by this pathway, Trost considered the possibility of migration of substituents. Therefore, 13C-labeled substrate 25 13C was used for this reaction. 

We (79TH1 81GEP3117363 84USP4588815) and others (87MI1) have studied acetylacetonato and rj -cp-rhodium complexes as catalysts in the pyridine formation [Eq.(l)]. Resin-attached cp-rhodium complexes are also active in the cocyclization of alkynes and nitriles, and the activity is... 

The cobalt catalyzed cocyclization of alkynes with heterofunctional substrates is not limited to nitriles. cpCo-core complexes are capable of co-oligomerizing alkynes with a number of C,C, C,N or C,0 double bonds in a Diels-Alder-type reaction. Chen, in our laboratories, has observed that these cycloadditions are best performed with the help of stabilizers such as ketones or acetic esters that are weakly coordinated to the cobalt and prevent the alkynes from being cyclotrimerized at the metal center... 

The nickel-catalysed 3 + 1 + 1-cycloaddition of alkenyl Fischer carbene complexes with methylenecyclopropanes produced the methylenecyclopentanone in high yields.169 The nickel-catalysed three-component 3 + 2 + 2-cocyclization of ethyl cyclopropylide-neacetate with two alkynes gave cycloheptadienes in good yields and high chemo- and regio-selectivity.170... 

Cocyclization of Two Molecules of Alkynes with Other Unsaturated Compounds... 

Other transition metal complexes catalyze interesting cocyclization of alkynes and alkenes by a completely different mechanism. Efficient 671-clcctrocyclization of the... 

The triple bond of the nitrile group can be cotrimerized with two alkynes to produce pyridines. The cobalt-catalysed cocyclization of alkyne and nitrile in a ratio of 2 1 is a good synthetic route to pyridine derivatives [70], Two regioisomers, 174 and 175, are obtained by the reaction of propyne with MeCN. The reaction is carried out in a large excess of MeCN, and potentially useful for commerical production of pyridine derivatives [71]. The reaction of acetylene itself with various nitriles produces the a-substituted pyridine 176 in the presence of water under irradiation [72], HCN cannot be used for this cocyclization. The reaction has been applied to alkaloid synthesis. 

A couple of prototypical examples of the cyclic version of the Heck reaction, defined as a process consisting of alkene carbopalladation followed by -elimination, were reported during the 1984-1985 period [9,10]. Almost concurrently, seminal examples of both the non-Heck cyclic carbopallation reactions [10,30] were reported during the 1983-1985 period. Thus, with due respect paid to earlier discoveries of alkyne cyclooligomerization via cascade carbopalladation [7,8] as well as copolymerization [24] and cocyclization [25,... 

Transition metal-catalyzed [2 + 2 + 2] cocyclization of two molecules of an alkyne with an alkene is a powerful method for forming 1,3-cyclohexa-dienes [29-31]. These compounds are of course valuable partners for Diels-Alder reactions [32]. Through the right choice of substrates, both [2 + 2 + 2] and [4 + 2] cycloadditions can be performed in a single chemical operation [33]. Indeed, the reaction of electroneutral diyne 14 with electron-deficient maleimide 15 in the presence of lmol% of a Ru(I) catalyst exclusively afforded the highly symmetrical 1 2 adduct 17 in 74% yield (Scheme 9). 

The cocyclization of alkyne dicobalt hexacarbonyl with alkenes is probably one of the most straightforward methods for the formation of cyclopentenones. " This formal [2 + 2 + 1] cycloaddition reaction was first reported by Khand... 

Compared with the Diels-Alder reaction, the [2+2+2]-cycloaddition is potentially more powerful since the number of new bonds as well as chirality centers that are formed is higher. Unfortunately, the reaction seems to be entropically or kinetically unfavorable. This disadvantage can, however, be overcome by the use of transition metal catalysts (templates). Among the most successful examples of this reaction type, the nickel(II) catalyzed Reppe reactions 96), the cobalt(I) catalyzed cocyclizations of a,to-diynes with alkynes 97), the cobalt(I) catalyzed pyridine synthesis 985 and last but not least the palladium(0) catalyzed cyclotrimerizations of 3,3-dialkylcyclopropenes to frans-cr-tris-homobenzenes must be mentioned. The latter has been known for ten years 99>. 

Numerous theoretically interesting hydrocarbons, like iptycenes [137b], starphenylenes (see Scheme 41 [140]) and highly strained threefold bicycloan-nelated benzenes (see Scheme 40 [139 a, c]) were synthesized by this very versatile approach. In addition, when alkynes are brought into a cocyclization reaction with alkyl and aryl nitriles or co-alkynyl isocyanates validated routes to heterocycles become available as it was demonstrated e. g. for the total synthesis... 

Nickel(0)-catalyzed [2 + 2 + 2] cocyclization of the precursor (177) in the presence of several chiral ligands afforded the chiral tetrahydroisoquinoline (178) in a novel asymmetric cycloaddition. Compound (178) could be transformed into the benzo[a]quinolizidine (180), albeit in modest enantiomeric excess, through a multistep route involving extension of the alkynic side chain at C-1 to yield (179), introduction of a cu halogen atom, reduction of the triple bond, A(-deprotection and final eyelization (Scheme 29) <94J0C6133>. 

Now analysis of the literature on palladium-catalyzed cyclotrimerizations suggests that arynes and alkynes have very different reactivities while arynes, which are strongly electrophilic, are efficiently cyclotrimerized by Pd(0) catalysts [ 39 ], there are few examples of efficient cyclotrimerization of alkynes using these complexes [61,62]. This difference in reactivity between arynes and alkynes in Pd-catalyzed cyclotrimerizations, rather than being a disadvantage, provides the chemoselectivity required for their cocyclization to be synthetically useful. Interestingly, cocyclizations of arynes and alkynes frequently show marked dependence on factors such as the electronic nature of the alkyne, the catalyst structure, or the reaction conditions. 

Although the palladium-catalyzed cocyclization of arynes and alkynes is still in its infancy, the synthetic potential of this novel methodology has already been explored. 

Other C-C bond-forming reactions have been successfully developed using SCCO2 and liquid CO2 as reaction media. Examples include the synthesis of cyclopentenones via cobalt-catalyzed cocyclizations of alkynes with alkenes and carbon monoxide (Pauson-Khand reaction) (Scheme 30) , enantioselective nickel-catalyzed hydrovinylation of styrenes (Scheme 31) , and the palladium-catalyzed hydroarylation of acyclic jS-substimted-o , j8-enones with aryl iodides (formal conjugate addition) (Scheme 32). ... 

Recently, the Yamamoto group and the Guitian group as pioneers in this field have developed efficient Pd-catalyzed reactions of arynes, particularly cyclotrimerization and cocyclization with alkynes, offering useful synthetic methods for polycyclic aromatic compounds [78]. The Spanish group reported that the cyclotrimerization of benzyne, generated from 251, occurred in situ at room temperature in the presence of Pd(PPh3)4 in MeCN, and obtained triphenylene (253) in 83 % yield [79]. 

Pd-catalyzed cocyclization of arynes with alkynes also proceeds smoothly. Yamamoto obtained phenanthrene derivatives exelusively in good yield, regardless of the electronie nature of the alkynes using Pd(OAe)2 and P(o-Tol)3. The reaction of 251 with 4-octyne gave rise to the phenanthrene 263 [82], Similarly, Perez carried out the reaction of benzyne with electron-dehcient alkynes such as dimethyl acetylenedi-carboxylate (DMAD) (264), and obtained the phenanthrene 265 as the main product using Pd(PPh3)4. On the other hand, when Pd2(dba)3 was used, the naphthalene derivative 266 was the main produet [83]. 

The reaction was first reported by Khand and Pauson et al. in 1973d It is the dicobalt octacarbonyl [Co2(CO)8l mediated or promoted one-step synthesis of a,p-unsaturated cyclopentenone from the [2+2+1] cycloaddition of alkyne, alkene and carbon monoxide, through an intermediate of alkynedicobalt hexacarbonyl complex. Therefore, this reaction is generally known as the Pauson-Khand reaction, Pauson-Khand cyclization, or Pauson-Khand cycloaddition. Occasionally, this reaction is also referred to as the Pauson-Khand annulation, Pauson-Khand multicomponent cycloaddition, Pauson-Khand carbonylative cocyclization, Pauson-Khand bicyclization, Khand annulation, Khand cycloaddition, Khand cyclization (cyclisation ), or Khand reaction.Among these names, the Pauson-Khand reaction is the one used most often. 

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