Ylide compounds carbene reactions

The reactions of carbenes, which are apparently unique in displaying electrophilic character in strongly basic solutions, include substitution, addition to multiple bonds, and co-ordination with lone pairs of electrons to form unstable ylides. This last reaction is of obvious relevance to a consideration of the reactions of heterocyclic compounds with carbenes and will be summarized. 

The preparation of novel phase transfer catalysts and their application in solving synthetic problems are well documented(l). Compounds such as quaternary ammonium and phosphonium salts, phosphoramides, crown ethers, cryptands, and open-chain polyethers promote a variety of anionic reactions. These include alkylations(2), carbene reactions (3), ylide reactions(4), epoxidations(S), polymerizations(6), reductions(7), oxidations(8), eliminations(9), and displacement reactions(10) to name only a few. The unique activity of a particular catalyst rests in its ability to transport the ion across a phase boundary. This boundary is normally one which separates two immiscible liquids in a biphasic liquid-liquid reaction system. 

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

In contrast to considerations of 50 years ago, today carbene and nitrene chemistries are integral to synthetic design and applications. Always a unique methodology for the synthesis of cyclopropane and cyclopropene compounds, applications of carbene chemistry have been extended with notable success to insertion reactions, aromatic cycloaddition and substitution, and ylide generation and reactions. And metathesis is in the lexicon of everyone planning the synthesis of an organic compound. Intramolecular reactions now extend to ring sizes well beyond 20, and insertion reactions can be effectively and selectively implemented even for intermolecular processes. 

The oxygen as heteroatom in ethers or carbonyl compounds is weak to moderate Lewis base. Nevertheless, a highly reactive metal carbene complex can interact with the oxygen to generate oxygen ylide. The interaction between ether and metal carbene functional groups is believed to be rather weak as demonstrated by the facts that other metal carbene reactions, such as G-H insertion and cyclopropanation, can proceed in ethereal solvents." These experiments demonstrate that the formation of the metal ylide is much less favored in the equilibrium shown in Equation (1). ... 

Carbenes are readily obtained by the photodecomposition of diazo-compounds. The reactions of carbenes generated in this way in rigid matrices at low temperatures have been reviewed. Addition of singlet methylene to acetonitrile affords the nitrile ylide... 

Ylide generation from diazo compounds by reaction of carbenoids is a better method than photochemical or thermal dediazoniation in the presence of organic substrates containing heteroatoms, because these dediazoniations without metal catalysis yield, in most cases, not very selective carbenes. Here again, the copper-catalyzed route is in most cases inferior to that with rhodium catalysts. The diazoketo ester with a terminal thioalkyl group (8.145) can be obtained from the... 

Rhodium(II) carbenoid intermediates are also useful. For example, carbene transfer reaction with allylic sulfides followed by [2,3]-sigmatropic rearrangement of the resulting sulfur ylides (Doyle-Kirmse reaction) gives furan-containing sulfides 133 in good yields (Scheme 19.32) [50]. In contrast, reaction with allylic compounds (R—H) or alcohols/amines/thiols/silanes (X—H) furnishes the 1,1-insertion products 134 or 135, respectively [51],... 

There have been a number of reports on the photochemical reaction between diazo-compounds and sulphides to form either stable or transient ylides. lllger et al. reported the isolation of a series of ylides from the reaction of dimethyl sulphide with substituted diazomethanes, such substituents being carbonyl, sulphonyl, or phosphoryl groups. Ando et of. described the reaction of diazo dimethyhnalonate with a series of sulphides but found that the yields of ylides varied considerably, much more so than for the thermal reaction, with the nucleophilicity of the sulphide. For example, dimethyl sulphide afforded an 88% yield of ylide (6a) while diphenyl sulphide afforded a 12% yield of ylide (6b). Repetition of the reaction with dimethyl sulphide but in the presence of cyclohexene indicated that the sulphide was about six times as reactive as the olefin toward the photochemically generated carbene. These reactions aU were assumed to occur by conversion of the diazo-compound into a singlet carbene, which attacked sulphur. However, it was found that (6a) also could... 

Electron deficient species can attack the unshared electron pairs of heteroatoms, to form ylides, such as in the reaction of thietane with bis(methoxycarbonyl)carbene. The S —C ylide rearranges to 2,2-bis(methoxycarbonyl)thiolane (Section 5.14.3.10.1). A"-Ethoxycar-bonylazepine, however, is attacked by dichlorocarbene at the C=C double bonds, with formation of the trans tris-homo compound (Section 5.16.3.7). 

These carbene (or alkylidene) complexes are used for various transformations. Known reactions of these complexes are (a) alkene metathesis, (b) alkene cyclopropanation, (c) carbonyl alkenation, (d) insertion into C-H, N-H and O-H bonds, (e) ylide formation and (f) dimerization. The reactivity of these complexes can be tuned by varying the metal, oxidation state or ligands. Nowadays carbene complexes with cumulated double bonds have also been synthesized and investigated [45-49] as well as carbene cluster compounds, which will not be discussed here [50]. 

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