Alkynes, metal mediated

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

The total synthesis of ( )-estrone [( )-1 ] by Vollhardt et al. is a novel extension of transition metal mediated alkyne cyclotrimeriza-tion technology. This remarkable total synthesis is achieved in only five steps from 2-methylcyclopentenone (19) in an overall yield of 22%. The most striking maneuver in this synthesis is, of course, the construction of tetracycle 13 from the comparatively simple diyne 16 by combining cobalt-mediated and ort/io-quinodimethane cycloaddition reactions. This achievement bodes well for future applications of this chemistry to the total synthesis of other natural products. 

M-substituted 2-pyridones can be prepared by N-alkylation, under basic conditions (pfCa of the amide proton is 11). The resulting anion can then react on either nitrogen or oxygen depending on the conditions employed [24-27]. Also, several direct methods for the construction of N-substituted 2-pyridones have been reported. Two such examples can be seen in Scheme 3 where the first example (a) is an intramolecular Dieckmann-type condensation [28] and the second (b) is a metal-mediated [2 -I- 2 + 2] reaction between alkynes with isocyanates [29,30]. 

Metal-mediated reductive coupling of alkenes and alkynes affords access to complicated organic structures, including carbocyclic and heterocyclic molecules, from readily available starting materials. While most of these coupling reactions were initially developed as stoichiometric processes, many selective, catalytic versions have been developed over the past decade these advancements have made reductive coupling much more attractive to synthetic chemists. 

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 . 

The metal-mediated and metal-catalyzed [6 + 2]- and [6 + 4]-cycloaddition reactions, pioneered by Pettit and co-workers105 106 and Kreiter and co-workers,107 respectively, involve the cycloaddition of metal-complexed cyclic trienes with 7r-systems such as alkenes, alkynes, and dienes. The [6 + 2]-reactions produce bicyclo[4.2.1]nonadiene derivatives and the [6 + 4]-reactions produce bicyclo[4.4.1]undecatrienes (Scheme 32). Trienes complexed to chromium, which can be prepared on large scale (40 g) as reported by Rigby and co-workers,108 react with 7r-systems upon thermolysis or irradiation.109-111 Chromium and iron-catalyzed [6 + 2]-reactions of cycloheptatrienes and disubstituted alkynes... 

Metal-mediated and -catalyzed [3 + 2 + 2]-higher-order cycloaddition reactions have also proved to be viable and mechanistically novel methods for the synthesis of seven-membered rings. The reported [3 + 2 + 2]-cycloadditions of allyliridium (Equation (30)),139 -allylcobalt (Scheme 47),140 and allylmanganese (Equation (31 ))141 complexes with alkynes involve the reaction of preformed allylmetal complexes with two separate alkynes, leading to a cycloheptadiene-metal complex. 

Like alkynes, a variety of mechanistic motifs are available for the transition metal-mediated etherification of alkenes. These reactions are typically initiated by the attack of an oxygen nucleophile onto an 72-metalloalkene that leads to the formation of a metal species. As described in the preceding section, the G-O bond formation event can be accompanied by a wide range of termination processes, such as fl-H elimination, carbonylation, insertion into another 7r-bond, protonolysis, or reductive elimination, thus giving rise to various ether linkages. 

Transition metal mediated or catalyzed benzene formation reactions have been reported using various metals. However, the use of three different alkynes is difficult [38], In many cases, a mixture of several benzene derivatives is obtained. In 1974, Wakatsuki and Yamazaki used three different alkynes with Co complexes [27b], but isomers were formed and a tedious chromatographic separation was necessary. The first selective coupling of three different alkynes in high yields was reported in 1995 using a combination of unsymmetrical zirconacydopentadienes and CuCl, as shown in Eq. 2.52 [7k]. 

The method enables conversion of substituted alkynes to (fc)-2-methyl-1 -alkenylalumi-num species, and, by subsequent iodinolysis, to the corresponding iodoalkenes with retention of the double-bond configuration. Depending on the substitution pattern of the starting alkyne, many useful products emerge from this reaction, which themselves can serve as building blocks for transition metal-mediated or -catalyzed coupling reactions [59—62]. 

Abstract The transition metal mediated conversion of alkynes, alkenes, and carbon monoxide in a formal [2 + 2+1] cycloaddition process, commonly known as the Pauson-Khand reaction (PKR), is an elegant method for the construction of cyclopentenone scaffolds. During the last decade, significant improvements have been achieved in this area. For instance, catalytic PKR variants are nowadays possible with different metal sources. In addition, new asymmetric approaches were established and the reaction has been applied as a key step in various total syntheses. Recent work has also focused on the development of CO-free conditions, incorporating transfer carbonylation reactions. This review attempts to cover the most important developments in this area. 

Cobalt, as its CpCo(CO)2 complex, has proven to be especially suited to catalyze [2 + 2 + 2] cycloadditions of two alkyne units with an alkyne or alkene. These cobalt-mediated [2 + 2 + 2] cycloaddition reactions have been studied in great detail by Vollhardt337. The generally accepted mechanism for these cobalt mediated cycloadditions, and similar transition metal mediated cycloadditions in general, has been depicted in equation 166. Consecutive co-ordination of two triple bonds to CpCo(CO)2 with concomitant extrusion of two molecules of carbon monoxide leads to intermediates 578 and 579 via monoalkyne complex 577. These react with another multiple bond to form intermediate 580. The conversion of 578 to 580 is said to be kinetically favored over that of 579 to 580. Because intermediates like 580 have never been isolated, it is still unclear whether the next step is a Diels-Alder reaction to form the final product or an insertion to form 581. The exact circumstances might determine which pathway is followed. 

Reduction of (312) has been found to afford the dimer (313) which upon heating rearranged to yield the unprecedented di(benzopentalene) complex (314). The regio- and stereo-specificity of the conversion (313) into (314) implies a metal-mediated pathway for the process (see Scheme 100). The first observable cis-bis(alkyne)cyclobutadiene rearrangement [see (315) to (316)] has been reported. 

The first examples of metal-mediated [5-1-2] cycloadditions between VCPs and tethered alkynes were reported in 1995 (Tab. 13.1) [21]. Initial success was obtained by treating alkyne-VCP 54 with Wilkinsoris catalyst ([RhCl(PPh3)3]) in refluxing toluene for 48 h to produce cycloadduct 55 in 84% yield. Further investigations led to the development... 

Superheated and supercritical water are used in several applications. Supercritical water is most often used in the destruction of organic wastes, including some chemical warfare agents, as an alternative to incineration (Katritzky et al., 1996 Sherman et al., 1998). Recent reports describe the use of both forms as a solvent and as a reactant in synthetic chemistry (Katritzky et al., 1996 An et al., 1997). Some of the reactions investigated include metal-mediated alkyne cyclizations, Pd-catalyzed al-kene arylations, aldol reactions, the Fischer indole synthesis, and hydrolysis reactions. Waterborne coatings and the destruction of wastes in supercritical water are fully... 

The final stages of the synthesis illustrate both the power and the current limitations of transition-metal mediated C-C bond formation. Coupling of 2 and 3 led to the ene-yne 7. Pd-mediated hydrostannylation of the alkyne proceeded with high geometric control, but tended to... 

Transition-metal mediated carbene transfer from 205 to benzaldehyde generates carbonyl ylides 211 which are transformed into oxiranes 216 by 1,3-cyclization, into tetrahydrofurans 212, 213 or dihydrofurans 214 by [3 + 2] cycloaddition with electron-deficient alkenes or alkynes, and 1,3-dioxolanes 215 by [3 + 2] cycloaddition with excess carbonyl compound120 (equation 67). Related carbonyl ylide reactions have been performed with crotonaldehyde, acetone and cyclohexanone (equation 68). However, the ylide generated from cyclohexanone could not be trapped with dimethyl fumarate. Rather, the enol ether 217, probably formed by 1,4-proton shift in the ylide intermediate, was isolated in low yield120. In this respect, the carbene transfer reaction with 205 is not different from that with ethyl diazoacetate121, whereas a close analogy to diazomalonates is observed for the other carbonyl ylide reactions. 

C-M bond addition, for C-C bond formation, 10, 403-491 iridium additions, 10, 456 nickel additions, 10, 463 niobium additions, 10, 427 osmium additions, 10, 445 palladium additions, 10, 468 rhodium additions, 10, 455 ruthenium additions, 10, 444 Sc and Y additions, 10, 405 tantalum additions, 10, 429 titanium additions, 10, 421 vanadium additions, 10, 426 zirconium additions, 10, 424 Carbon-oxygen bond formation via alkyne hydration, 10, 678 for aryl and alkenyl ethers, 10, 650 via cobalt-mediated propargylic etherification, 10, 665 Cu-mediated, with borons, 9, 219 cycloetherification, 10, 673 etherification, 10, 669, 10, 685 via hydro- and alkylative alkoxylation, 10, 683 via inter- andd intramolecular hydroalkoxylation, 10, 672 via metal vinylidenes, 10, 676 via SnI and S Z processes, 10, 684 via transition metal rc-arene complexes, 10, 685 via transition metal-mediated etherification, overview,... 

Reactions of alkynyliodonium salts 119 with nucleophiles proceed via an addition-elimination mechanism involving alkylidenecarbenes 120 as key intermediates. Depending on the structure of the alkynyliodonium salt, specific reaction conditions, and the nucleophile employed, this process can lead to a substituted alkyne 121 due to the carbene rearrangement, or to a cyclic product 122 via intramolecular 1,5-carbene insertion (Scheme 50). Both of these reaction pathways have been widely utilized as a synthetic tool for the formation of new C-C bonds. In addition, the transition metal mediated cross-coupling reactions of alkynyliodonium salts are increasingly used in organic synthesis. 

Metal-mediated intramolecular addition of silyl enolates to alkynes is also valuable for the synthesis of cyclic ketones. A stoichiometric amount of HgCl2 or EtAlCl2 effectively promotes the cycloalkenylation via anti-addition to alkynes (Equations (87) and (88)).319 320a The -addition mode can be explained by a metal coordination to the triple bond and subsequent attack of the enolate moiety from the opposite side to the metal. The resultant alkenylmetals can be used for carbon-carbon and carbon-heteroatom bond formation as well as protonation. 

Numerous transition metal-mediated [2 + 2+2] cycloadditions have been utilized in the synthesis of pyridines . Selective cyclotrimerization of alkynes with nitriles leads to pentasubstituted pyridines 310 with minimal formation of benzenoid byproducts (Scheme 157) <20000L3131>. Different alkynes can be utilized in the same strategy if a sequential approach is used (Scheme 158) <2000JA4994>. 

The metal mediated synthesis of cyclopentenones via a [2 + 2+1] cycloaddition between an alkyne, an alkene and carbon monoxide has become commonly known as the Pauson-Khand (PK) reaction. This report will briefly summarise some of the major developments since its initial discovery including an intramolecular variant of the reaction, the progress made towards making the process catalytic and examples of how the reaction has been utilised. The proposed mechanism for the reaction and the factors that influence the product distribution will also be introduced. 

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