General methods for generation of carbenes

Under the usual conditions one equivalent of the diazoalkane is consumed by the liberated acid but this can be avoided by use of an added base such as triethylamine/ Cyclic a-diazoketones, which are not available from acid chloride, can be prepared by reaction of a nucleophilic derivative such as the a-hydroxymethylene enolate with arylsulfonyl azides. Several combinations of carbon nucleophile and sulfonyl 

Addition of certain copper salts to solutions of diazo compounds also leads to evolution of nitrogen and formation of products of the same general types as those formed in thermal and photochemical decompositions of diazoalkanes. The weight of the evidence, however, indicates that free carbene intermediates are not involved in such reactions. Instead, complexes of the carbene unit with the metallic catalyst 

For a review of available synthetic methods, see E. Schmitz, Dreiringe mit Zwei Heteroatomen, Springer Verlag, Berlin (1967), pp. 114-121. 

Both phase transfer and crown ether catalysts have been used to promote a eliminations from chloroform and other haloalkanes. Various trialkylammonium hydroxides catalyze formation of dichlorocarbene in the organic phase of two phase systems consisting of CHCI3 and 50% sodium hydroxide solution. 

Weber and G. W. Gokel, Phase Transfer Catalysis in Organic Synthesis Springer Verlag, New York (1977), Chaps. 2-4. 

5 R2CH-X halides strong base or organometallic compounds R2C + BH + X- 

Decomposition of diazo compounds to carbenes is a quite general reaction. Examples include the simplest diazo compound, diazomethane, as well as diaryl diazomethanes and diazo compounds in which one or both of the substituents is an acyl group. The inability to synthesize the required diazo compound is sometimes a limitation on the method. The low-molecular-weight diazoalkanes are toxic and unstable, and are usually prepared and used in situ rather than isolated. The simple aliphatic diazo compounds are synthesized from derivatives of the corresponding amine. All the common precursors of diazomethane, for example, are derivatives of methylamine. The details of the base-catalyzed decompositions vary somewhat from 

CHAPTER 8 REACTIONS INVOLVING ELECTRON-DEFICIENT INTERMEDIATES 

Another route to diazo compounds is by oxidation of the corresponding hydrazone. This route is most frequently employed when at least one of the substituents is an aromatic group. 

When an a-diazoketone is needed, the usual synthesis starts with an acid halide. Reaction with a diazoalkane gives the diazoketone as a result of nucleophilic attack, with displacement of the chloride ion  

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The intramolecular addition of acylcarbene complexes to alkynes is a general method for the generation of electrophilic vinylcarbene complexes. These reactive intermediates can undergo inter- or intramolecular cyclopropanation reactions [1066 -1068], C-H bond insertions [1061,1068-1070], sulfonium and oxonium ylide formation [1071], carbonyl ylide formation [1067,1069,1071], carbene dimerization [1066], and other reactions characteristic of electrophilic carbene complexes. 

Other possible carbene precursors (vicinal dihalides, peresters, ketenes, carbene adducts with stable hydrocarbons, etc.) cannot generally be used for in situ generation of carbenes, because the fragments are likely to recombine. However, they can be used, for example, in experiments involving pyrolysis or other forms of external carbene generation where the fragments get a chance to separate in the gas phase and become trapped in distant matrix sites. AU conceivable halo- and dihalocar-benes were made and smdied in this way (see, e.g., the 1993 review by Sander et al." ) However, such methods can only be applied to carbenes which resist thermal rearrangement to more stable products. 

Scheme 7. General method for the preparation of PAHs by insertion reactions of carbenes generated by the thermal acetylene to vinylidene-carbene rearrangement [53b, 54a]...

In the 1988-1999 period, almost all absolute kinetic studies of carbenic reactions employed LFP with UV detection. Carbenes that contain a UV chromophore (e.g., PhCCl) are easily observed, and their decay kinetics during reaction can be readily followed by LFP.11 However, alkyl, alkylhalo, and alkylacyloxycarbenes are generally transparent in the most useful UV region. To follow their kinetics, Jackson et al. made use of the ylide method, 12 in which the laser-generated carbene (2) is competitively captured by (e.g.) pyridine, forming a chromophoric ylide (3, cf. Scheme 1). The observed pseudo first order rate constants (kobs) for the growth of ylide 3 at various concentrations of pyridine are monitored by UV spectroscopy, and obey Eq. 1. 

Although pyrolysis of several phenyl-substituted cyclopropanes results in extrusion of phenyl-carbene, which undergoes addition to C-C double bonds and forms phenylcyclopropanes under the experimental conditions employed, the overall efficiency of the process is generally too low to make it an attractive method for synthesis on a preparative scale. Thus, phenylcarbene, generated by photolysis of trans-l,2-diphenylcyclopropane or 1,2,3-triphenylcyclo-propane, forms 2-ethyl-2-methyl-1-phenylcyclopropane in only 6% yield as a mixture of isomers when the reaetions are carried out in 2-methylbut-l-ene. ... 

According to the nature of alkene metathesis, this general reaction can be divided into different subgroups cross-metathesis (CM), ring-closing metathesis (RCM), ringopening metathesis polymerization (ROMP), and acyclic diene metathesis polymerization (ADMET). " From an industrial perspective, a more cost-effective method for alkene metathesis is to generate the metallo-carbene in situP This reaction has been extensively reviewed. ... 

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