Transformations Involving Metal Carbenoids

Catalysis of dediazoniation reactions of aliphatic diazo compounds by transition metals has been known since the beginning of this century. 

The understanding of this catalysis started in 1952, shortly after the concept of carbenes was introduced (see Sect. 8.1). Yates postulated that transition-metal catalysts react with diazo compounds by formation of transient electrophilic metal carbenes, because that complex can be depicted as a metal-stabilized carbocation (8.104). Doyle (1986 a) proposed the catalytic cycle (8-46) for the formation of the carbenoid 8.104 and its reaction with an electron-rich substrate S . The reagent S is, first of all, an alkene in cyclopropanation, but can also belong to other groups of compounds, to be discussed later in this section. 

Until the end of the 1970 s, interest in such reactions concentrated on catalysis by copper salts (review Burke and Grieco, 1979), obviously influenced by the long, broad, and successful experience with copper +- and copper-ions in aromatic diazo chemistry (Sandmeyer, Pschorr and Meerwein reactions, see Zollinger, 1994, Chapts. 8 and 10). A landmark was the discovery of Salomon and Kochi (1973), who found that cyclopropanations with diazomethane in the presence of copper(i) trifluoromethanesulfonate (triflate OTf) resulted in reduction of Cu + to Cu +, and that the rate of dediazoniation is inversely proportional to the alkene concentration. These results strongly indicate that formation of an alkene-Cu+ complex (8-47 2) precedes the complex formation with the diazoalkane. 

In copper chelates like bis(acetylacetonato)-copper(ii) (Nozaki et al., 1966), formation of alkene complexes is negligible (at least not detectable). The comparison 

Palladium(ii) and rhodium(ii) acetates were introduced by Teyssie s group (Pd Paulissen et al., 1972 Rh Paulissen et al., 1973). They differ from one another in their ability to coordinate with alkenes and have, therefore, a different regio- and substrate specificity (Anciaux et al., 1980). Cobalt complexes are first of all interesting because of their effect on enantioselectivity. We will discuss them in Section 8.8. Here, we emphasize only that enantioselectivity provides the most convincing evidence for the involvement of metal-carbene intermediates in cyclopropana-tions. 

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In the laboratory of G.A. Sulikowski, an enantioselective synthesis of a 1,2-aziridinomitosene, a key substructure of the mitomycin antitumor antibiotics, was developed. Key transformations in the synthesis involved the Buchwald-Hartwig cross-coupling and chemoselective intramolecular carbon-hydrogen metal-carbenoid insertion reaction. 

The most generally employed approach for the formation of cyclopropanes is the addition of a carbene or carbenoid to an alkene. In many cases, a free carbene is not involved as an actual intermediate, but instead the net, overall transformation of an alkene to a cyclopropane corresponds, in at least a formal sense, to carbene addition. In turn, the most traditional method for effecting these reactions is to employ diazo compounds, R R2 —N2, as precursors. Thermal, photochemical and metal-catalyzed reactions of these diazo compounds have been studied thoroughly and are treated separately in the discussion below. These reactions have been subjects of several comprehensive reviews,8 to which the reader is referred for further details and literature citations. Emphasis in the present chapter is placed on recent examples. 

A select number of transition metal compounds are effective as catalysts for carbenoid reactions of diazo compounds (1-3). Their catalytic activity depends on coordination unsaturation at their metal center which allows them to react as electrophiles with diazo compounds. Electrophilic addition to diazo compounds, which is the rate limiting step, causes the loss of dinitrogen and production of a metal stabilized carbene. Transfer of the electrophilic carbene to an electron rich substrate (S ) in a subsequent fast step completes the catalytic cycle (Scheme I). Lewis bases (B ) such as nitriles compete with the diazo compound for the coordinatively unsaturated metal center and are effective inhibitors of catalytic activity. Although carbene complexes with catalytically active transition metal compounds have not been observed as yet, sufficient indirect evidence from reactivity and selectivity correlations with stable metal carbenes (4,5) exist to justify their involvement in catalytic transformations. 

While most of the initial studies have involved the transition metal-catalyzed decomposition of a-carbonyl diazo compounds and have been reviewed [3-51], it appears appropriate to highlight again some milestones of these transformations, since polycyclic structures could be nicely assembled from acyclic precursors in a single step. Two main reactivities of metalo carbenoids derived from a-carbonyl diazo precursors, namely addition to a C - C insaturation (olefin or alkyne) and formation of a ylid (carbonyl or onium), have been the source of fruitful cascades. Both of these are illustrated in Scheme 27 [52]. The two diazo ketone functions present in the same substrate 57 and under the action of the same catalyst react in two distinct ways. The initially formed carbenoid adds to a pending olefin to form a bi-cyclop. 1.0] intermediate 58 that subsequently cyclizes to produce a carbonyl ylide 59, that is further trapped intramolecularly in a [3 + 2] cycloaddition. The overall process gives birth to a highly complex pentacyclic structure 60. 

The chemistry of copper carbenoids involved in the catalytic decomposition of diazo compounds and related tosylhydrazones has been reviewed. Many aspects of these catalytic transformations are covered including not only the classical cyclopropanation and X-H insertion processes but also a range of formal cycloaddition reactions, the reactions involving ylide formation, and the various coupling reactions of diazo derivatives. An account more focused on asymmetric metal-catalysed X-H insertion has been published. Through this review, the dependence on the nature of the metal and its i ligands can be evaluated for these 0-H, N-H, S-H, and Si-H insertions of carbenoids. 

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