Carbenes, generation methylene

Reactions involving free carbenes are very exothermic since two new theoretical treatment of the addition of singlet methylene to ethylene suggests that there is no activation barrier.168 The addition of carbenes to alkenes is an important method for synthesis of many types of cyclopropanes and several of the methods for carbene generation listed in Scheme 10.8 have been adapted for use in synthesis. Scheme 10.9, at the end of this section, gives a number of specific examples. 

CARBENE. The name quite generally used for the methylene radical, CH,. It is formed during a number of reactions. Thus the flash photochemical decomposition of ketene (CH2=C=0) has been shown to proceed in two stages. The first yields carbon monoxide and CHj. the latter then reacting with more ketene to form ethylene and carbon monoxide. Carbcne reacts by insertion into a C- H bond to form a C-CH, bond. Thus carbene generated from ketene reacts with propane to form, i-butane and isobutane. Carbene generated by pyrolysis uf diazomethane reacts with diethyl ether to form ethylpropyl ether and ethylisopropyl ether. 

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). 

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... 

Photolysis of diazo compounds (305) generates nitrogen and the carbene 289. Photolysis of diazomethane (311, R = H), for example, generates methylene (H2C ),242 Benzophenone is often added as a sensitizer for the photolysis of diazomethane. Under these conditions, triplet methylene is formed via intersystem crossing (5i Ti)243 (sec. II.IO.B). Energy transfer from triplet benzophenone to triplet diazomethane followed, and triplet diazomethane decomposed to triplet methylene.244 a similar thermal reaction gives the carbene and the usual carbene reactions.245... 

In Section 8.1 it was briefly discussed that carbenes react with benzene leading to various products (8-3). With photolytically generated methylene, toluene and cycloheptatriene are obtained in the ratio 1 3.5 (Doering et al., 1953 products with... 

The discussion to this point has concerned only the parent carbene and methylene. The same structural principles generally apply to other carbenes, but there are some additional considerations. For example, diphenylcarbene is more nearly linear due to the steric repulsion of the two phenyl groups. In a study of diphenylcarbene generated in diphenylethene crystals, the Cph-C-Cph bond angle was found to be 148°, and the phenyl rings were twisted 36° out of the plane defined by the carbene carbon atom and two-ring carbon atoms bonded to it. 

More useful for synthetic purposes, however, is the combination of the zinc-copper couple with methylene iodide to generate carbene-zinc iodide complex, which undergoes addition to double bonds exclusively to form cyclopropanes (7). The base-catalyzed generation of halocarbenes from haloforms (2) also provides a general route to 1,1-dihalocyclopropanes via carbene addition, as does the nonbasic generation of dihalocarbenes from phenyl(trihalomethyl)mercury compounds. Details of these reactions are given below. 

The reaction of methyl acrylate and acrylonitrile with pentacarbonyl[(iV,iV -di-methylamino)methylene] chromium generates trisubstituted cyclopentanes through a formal [2S+2S+1C] cycloaddition reaction, where two molecules of the olefin and one molecule of the carbene complex have been incorporated into the structure of the cyclopentane [17b] (Scheme 73). The mechanism of this reaction implies a double insertion of two molecules of the olefin into the carbene complex followed by a reductive elimination. 

A relatively unique type of reactive metabolite is carbene, i.e., a divalent carbon, which is a proposed intermediate in the oxidation of methylene dioxy-containing compounds. A methylenedioxy group in aromatic compounds is subject to O-dealkylation, e.g., 3,4-methylenedioxyamphetamine, as shown in Figure 8.20. The process generates formic acid and the catechol metabolite as final products. However, in the course of the reaction, a... 

If chiral catalysts are used to generate the intermediate oxonium ylides, non-racemic C-O bond insertion products can be obtained [1265,1266]. Reactions of electrophilic carbene complexes with ethers can also lead to the formation of radical-derived products [1135,1259], an observation consistent with a homolysis-recombination mechanism for 1,2-alkyl shifts. Carbene C-H insertion and hydride abstraction can efficiently compete with oxonium ylide formation. Unlike free car-benes [1267,1268] acceptor-substituted carbene complexes react intermolecularly with aliphatic ethers, mainly yielding products resulting from C-H insertion into the oxygen-bound methylene groups [1071,1093]. 

This reaction apparently proceeds by way of the normal phosphonate condensation product, the diazoalkylidene, which then spontaneously loses nitrogen to form the transient alkylidene car-bene. Careful work showed that, after statistical corrections were applied, the reactivity of a C-H bond toward insertion was approximately 0.003 for primary C-H bonds (methyl), 1.0 for secondary C-H bonds (methylene), 7.5 for benzylic (methylene) C-H bonds and 18.6 for tertiary C-H bonds. These relative reactivities are very similar to those previously observed for intramolecular C-H insertion by an alkylidene carbenoid generated from a vinyl bromide27. It was shown subsequently that the alkylidene carbene insertion reaction proceeds with retention of absolute configuration28. Using this approach, (l )-3-dimethyl-3-phenyl-l-cyclopentene and (i )-4-methyl-4-phenyl-2-cyclohexcnonc were prepared in high enantiomeric purity. 

Benzene derivatives such as m-methylanisole (40) can be converted to distonic carbene ions. Reaction of 40 with O occurs with loss of H2, generating the conventional carbene anion 41 this anion reacts with molecular fluorine by dissociative ET, followed by nucleophilic attack of F on the methyl group, forming 42. In contrast to phenyhnethylene, 42 has a singlet ground state however, upon protonation it gives rise to the triplet state of m-hydroxyphenyl-methylene. This interesting reaction can be viewed as a spin-forbidden proton-transfer reaction. 

In the light of experimental difficulties associated with the identification of intermediates, a MINDO/3 quantum-mechanical study of the singlet state ( a2) of the cyclobutylidene to methylenecyclopropane rearrangement has been carried out. It has been proposed that the whole process is initiated by electrophilic attack from the C3 methylene group of cyclobutylidene at the empty p atomic orbital on the Cl carbene site, so that a shift of electron density towards Cl can take place to give the bicyclobutane-like nonclassical carbene intermediate 4. Finally, the bicyclobutane intermediate 4 undergoes a symmetry-allowed conrotatory bond-fission process to generate methylenecyclopropane. The activation enthalpy calculated for the two steps is 8 kcal mol-1.2... 

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