Alkynes, metal mediated reaction with

Other metal-mediated reactions of azide reagents to terminal alkynes have also been reported. Indium(ll) triflate catalyzed tandem azidation/l,3-dipolar cycloaddition of various (o,(o-dialkoxyalkynes 134 with trimethylsilyl azide yielded fused 1,2,3-triazoles 135 <05TL8639>. A new ruthenium-catalyzed process for the regioselective synthesis of 1,5-disubstituted-1,2,3-triazoles has been developed <05JA15998>. 

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... 

Herein, we review nonexhaustively our contribution to the field of transition-metal-mediated heterocyclic synthesis. This chemistry is based mainly on using cyclopalladated complexes and their reactions with disubstituted alkynes that in many cases, lead to heterocyclic products by the selective intramolecular formation of carbon-carbon and carbon-heteroatom (C-N, C-O and C-S) bonds. In some instances these reactions also lead to interesting carbocyclic derivatives. Emphasis is placed on the transformations of the alkynes. When they are allowed to react with the metallated ligands, they lead in several instances to heterocyclic or carbocyclic final products. We present in particular some of the more recent results emanating from our laboratory and comment briefly on some similarities of this chemistry to other, selected and related transition-metal-mediated reactions, thus demonstrating that this field of research remains in vogue in many different research groups. 

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. 

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]. 

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. 

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. 

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. 

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. 

A catalytic tandem cyclopropanation-ring-closing metathesis of dienyne 80 led to derivative 81 in good yield (Scheme 30 <2004JA9524>). For internal alkynes, carbene-mediated ring-closing enyne metathesis was observed. Less favorable alkyne binding leads to preferential reactions of the metal carbene with the 1-alkene moiety. 

Metal mediated and catalyzed reactions have made significant contributions to organic synthesis over the past two decades [1]. One of the earliest and most useful of these is the Pauson-Khand carbon-carbon coupling reaction [2] first reported in 1971. In this reaction, a cyclopente-none is formed from an alkyne and an alkene in the presence of [Co2(CO) ] with insertion of carbon monoxide in a formal 12-h2+1 ]-cycloaddi-tion. The exceptional potential of this reaction has been demonstrated in many (mostly intramolecular) syntheses (Scheme 1) [3]. 

Cp Rh(MeCN)(/r-CH2)]2 +, both methylene units couple with two alkyne molecules see Organic Synthesis Using Metal-mediated Coupling Reactions) to form (146). ... 

A considerable number of reactions of CpRh(/x-CO)(/x- ) ) -F3CC=CCF3)RhCp have been reported which illustrates the diversity of products that can be obtained in transition metal alkyne chemistry see Organic Synthesis Using Metal-mediated Coupling Reactions). Reaction of this complex with dimethyldiazomethane forms a mixtme of (147) and (148), and on recrystallization (148) converts to (149) by... 

Metallacycles have been claimed to play pivotal roles in many transition metal-mediated multi-component coupling reactions [1]. For example, [2 -i- 2 -i- 2] alkyne cyclo-trimerization leading to benzenes - the Reppe reaction - has been considered to proceed via metallacyclopentadiene and elusive metallacycloheptatriene intermediates ("common mechanism ), while metallacyclopentenes have been proposed as intermediates for the [2 -i- 2 -i- 1] cyclo-coupling reactions of an alkyne, an alkene, and CO leading to a cyclopentenone (the Pauson-Khand reaction). A metallacyclic compound - which is defined here as a carbocyclic system with one atom replaced by a transition metal element - can be generally formed by oxidative cyclization of two unsaturated molecules with a low-valent transition metal fragment [2-4]. Alter-... 

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