Alkenes, metal-mediated

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. 

Although transition metal-mediated P-H addition across ordinary alkenes proceeds well only with five-membered cyclic hydrogen phosphonates, addition across the olefinic linkage of a,P-unsaturated compounds occurs readily with a range of phosphorus species and catalytic agents. Of particular note are the reaction systems involving platinum,96-107 palladium,108-115 and the lanthanides.116-122... 

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... 

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. 

The reaction mechanisms of these transition metal mediated oxidations have been the subject of several computational studies, especially in the case of osmium tetraoxide [7-10], where the controversy about the mechanism of the oxidation reaction with olefins could not be solved experimentally [11-20]. Based on the early proposal of Sharpless [12], that metallaoxetanes should be involved in alkene oxidation reactions of metal-oxo compounds like Cr02Cl2, 0s04 and Mn04" the question arose whether the reaction proceeds via a concerted [3+2] route as originally proposed by Criegee [11] or via a stepwise [2+2] process with a metallaoxetane intermediate [12] (Figure 2). 

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. 

As intuitively deduced, coordinating Y and Z must be removed or displaced in order for alkenes to coordinate and form an alkene tr-complex (Scheme 2). Since these intermediates, Cp 2MR(alkene), have never been observed in any detectable amounts for early transition metal-mediated polymerization, several chelate model systems have been devised (Figure 3). 

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. 

The selective oxidation of C—H bonds in alkanes under mild conditions continues to attract interest from researchers. A new procedure based upon mild generation of perfluoroalkyl radicals from their corresponding anhydrides with either H2O2, m-CPBA, AIBN, or PbEt4 has been described. Oxidation of ethane under the reported conditions furnishes propionic acid and other fluorinated products.79 While some previously reported methods have involved metal-mediated functionalization of alkanes using trifluoroacetic acid/anhydride as solvent, these latter results indicate that the solvent itself without metal catalysis can react as an oxidant. As a consequence, results of these metal-mediated reactions should be treated with caution. The absolute rate constants for H-abstraction from BU3 SnH by perfluorinated w-alkyl radicals have been measured and the trends were found to be qualitatively similar to that of their addition reactions to alkenes.80 a,a-Difluorinated radicals were found to have enhanced reactivities and this was explained as being due to their pyramidal nature while multifluorinated radicals were more reactive still, owing to their electrophilic nature.80... 

The same authors have demonstrated that 1,3-diynes behave in predictable yet distinctive manners compared to simple enynes under electrophilic transition metal-mediated reaction conditions. This characteristic behaviour of 1,3-diynes is presumably caused by the slightly electron-withdrawing nature of the alkynyl substituent, which not only renders preferentially the formation of 5-exotype alkylidenes but also allows for the subsequent [l,3]-metallotropic shift. Several salient features of reactions with this functionality include the following (a) an acetate is more reactive than the tethered alkene as an initiator, generating [l,2]-acetate migrated alkylidene intermediate, whereas an alkene is a better terminator than an acetate/bromide to generate the cyclopropane moiety (b) allene products are not formed at all under current reaction conditions (c) 5-exo/6-endo-type alkylidene formation depends on the heteroatom substituent in the tether (d) facile metallotropic [1,3]-shift of the intermediate alkylidenes occurred whenever possible. 

Palladium chemistry has been used in the synthesis of tetrahydroisoquinolines. Different combinations of iodoaryl-amine-alkene can be used in these multicomponent reactions. For example, the metal-mediated o-alkylated/alkenyl-ation and intramolecular aza-Michael reaction (Scheme 109) give moderate yields of heterocycle <2004TL6903>, whereas the palladium-catalyzed allene insertion-nucleophilic incorporation-Michael addition cascade (Equation 172) produces good yields of tetrahydroisoquinolines in 15 examples <2003TL7445> with further examples producing tetrahydroquinolines (Scheme 110) <2000TL7125>. 

The activation of oxygen in oxygen transfer reactions is usually mediated by a suitable transition metal catalyst which has to be sufficiently stable under the reaction conditions needed. But also non-metal catalysts for homogeneous oxidations have recently been of broad interest and several of them have been compiled in a recent review.2 Other examples for well known alkene oxidation reactions are the ozonolysis, hydroboration reactions or all biological processes, where oxygen is activated and transferred to the substrate. Examples for these reactions might be cytochrome P450 or other oxotransferases. Of these reactions, this contribution will focus on transition-metal mediated epoxidation and dihydroxylation. 

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. 

Figure 6.7 (Below) Metal-mediated alkene isomerization via (a) allyl or (b) hydride intermediates...

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]. 

Branching can resnlt from the chain-growth process or from branching gronps in the monomers. For example, ethylene can be polymerized by a radical process to a highly branched low-density polyethylene (LDPE) or copolymerized with small amounts of a-alkenes like 1-hexene or 1-octene nsing a metal-mediated catalyst the resnlt is a linear polyethylene punctuated by short-chain branches and known as linear-low-density polyethylene (LLDPE). 

Metal aUcylidene complexes (see Schrock-type Carbene Complexes) have been proposed as intermediates in many catalytic reactions, including alkene metathesis (see Organic Synthesis Using Metal-mediated Metathesis Reactions), alkene and aUcyne polymerization, methylenation of carbonyl compounds, and cyclopropanation of alkenes. ... 

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