Carbenes, generation reactivity

Hindered lithium dialkylamides can generate aryl-substituted carbenes from benzyl halides.162 Reaction of a,a-dichlorotoluene or a,a-dibromotoluene with potassium r-butoxide in the presence of 18-crown-6 generates the corresponding a-halophenylcarbene.163 The relative reactivity data for carbenes generated under these latter conditions suggest that they are free. The potassium cation would be expected to be strongly solvated by the crown ether and it is evidently not involved in the carbene-generating step. 

The difference in reactivity between isoprenol and isoprenyloxide, methal-lyl methyl ether and methallyloxide were investigated in the reaction with (phenylthio)carbene generated under phase-transfer conditions. With isoprenol, (phenylthio)methyl ether (41%) was the major product, whereas with methyl ether cyclopropanation (36%) was the sole reaction.1519 With alkoxides, in contrast, the major product was the C-H insertion product (45%) and (phenyl-... 

The reactivity of heterocyclic systems with carbenes, generated under phase-transfer catalytic conditions, has been reviewed for the period up to 1983 [1]. Most unsaturated non-heteroaromatic systems react with carbenes in the manner expected of alkenes, amines, amides, ketones, etc. (see Sections 7.3,7.5 and 7.6). 

Ethers, sulfides, amines, carbonyl compounds, and imines are among the frequently encountered Lewis bases in the ylide formation from such metal carbene complex. The metal carbene in the ylide formation can be divided into stable Fisher carbene complex and unstable reactive metal carbene intermediates. The reaction of the former is thus stoichiometric and the latter is usually a transition metal complex-catalyzed reaction of a-diazocarbonyl compounds. The decomposition of a-diazocarbonyl compounds with catalytic transition metal complex has been the most widely used approach to generate reactive metal carbenes. For compressive reviews, see Refs 1,1a. 

Carbenes, generated by several methods, are reactive intermediates and used for further reactions without isolation. Carbenes can also be stabilized by coordination to some transition metals and can be isolated as carbene complexes which have formal metal-to-carbon double bonds. They are classified, based on the reactivity of the carbene, as electrophilic heteroatom-stabilized carbenes (Fischer type), and nucleophilic methylene or alkylidene carbenes (Schrock type). 

Of lesser relevance to this discussion are halogenation methods involving the modification of the carbon skeleton (synthesis and degradation). The Hunsdiecker reaction, as applied to certain heterocyclic acids, has had limited application for the synthesis of halogen derivatives. The preparation of 3-bromo-4,6-dimethyl-2-pyridone from the silver salt of the respective 3-carboxylic acid by treatment with bromine in carbon tetrachloride is a rare example of success.13 The interaction of carbenes with heterocycles also has been employed infrequently, but recent advances in carbene generation may reactivate this approach.14 The Ciamician-Dennstedt ring expansion of pyrrole to / -halopyridines is a case in point18 [Eq. (4)] ... 

Despite the expected enhanced reactivity of trifluoromethyl-substituted carbenes as electrophilic species, yields in their [2+ l]-cycloaddition reactions with alkenes are highly dependent on the nature of the second substituent of the carbene. Furthermore, the method of carbene generation has a large influence on carbene reactivity. 

The generation of stannyne 58 by the photolysis of diazomethyl-substituted stannylene 57 was reported by Kira et al. (Scheme 2.9.22). The formation of 59 is explained by the intermediacy of stannyne 58, followed by the intramolecular insertion of the carbene moiety of 58 into the proximate methyl C—H bond of the isopropyl group. This result afforded evidence not only for the generation of 58 but also for its high carbene-like reactivity. 

All of these carbenes are reactive intermediates that must be generated from the appropriate precursors in the presence of the alkene (or arene) which is to be cyclopropanated. The following methods of carbene-transfer reactions to C-C double bonds will be discussed path a. from a-halo-a-metal (or alkylmetal) compounds by a-elimination path b. from iodine or sulfur ylides by thermal, photochemical or transition metal catalyzed decomposition ... 

Typically, C-C double bonds bearing one to four alkyl substituents were cyclopropanated. Methoxy(trifluoromethyl)carbene, generated by photochemical decomposition of 3-methoxy-3-trifluoromethyldiazirine, cyclopropanated both electron-rich (2-methylpropene, 2-methyl-but-1-ene, 2-methyl-but-2-ene) and electron-deficient C-C double bonds (acrylonitrile, ethyl acrylate) however, very low reactivity towards 2,3-dimethylbut-2-ene was observed for steric reasons (see Section 1.2.1.6.). °... 

Homothiophene and homofuran (10, X = S, O) are the most reactive substrates. They are easily prepared by carbene addition (using diazomethane as carbene precursor) to thiophene and furan, respectively. Since carbene insertion into the a-carbon-hydrogen bond of diethyl ether (which is usually used as a solvent) competes with carbene addition to the aromatic system, the diazomethane solution for carbene generation is most conveniently prepared using the reactant as solvent. ... 

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