The Reactions of Carbenes

At the same time, according to the calculations [35], trimethylene cannot exist as a free-energy intermediate at accessible temperatures. The question whether substituted trimethylenes can correspond to intermediates remains, however, open. In greater detail this problem is discussed in Ref. [35] where ample literature is given about ab initio and semiempirical studies. 

In order to predict transformations of biradicals, it is important to know the magnitude of the singlet-triplet gap, since the multiplicity of a biradical affects in an essential manner its reactivity. This may be illustrated by the well-known example of the reactions of 1,1-biradicals, namely, the carbenes considered below in the next section. In the case of l,j-biradicals, it is a general rule that the stability of the singlet electronic state of a biradical is assisted by increased overlapping of the terminal obritals the triplet state represents the ground state when this overlap is small [28, 36]. Ordinarily the S-T gap does not exceed 4-5 kcal/mol in the case of the l,j-biradicals. 

The effect of multiplicity of carbenes on their reactivity is most vividly marked in the following features rationalized by Skell et al. from experimental data [37-39]. First, the reaction of carbenes occurs in the singlet electron state at a much faster rate than in the triplet, with the absolute rates of typical reactions of addition to multiple bonds and of insertion into the C—H bonds exceeding, under normal conditions, the rate of intercombination conversion. Secondly, the singlet carbenes are characterized by one-step stereospecific addition to double bonds, as, for instance, in the cyclopropanation reaction, while the triplet carbenes react in a nonstereospecific way to form first an intermediate biradical through addition to one of the atoms of the double bond. The formation of a trimethylene radical, in the course of reaction of triplet methylene ( B ) with ethylene, has been confirmed by semiempirical [40, 41] and ab initio [42, 43] quantum chemical calculations. 

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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 reactions of carbenes are more varied than those of the species previously discussed in this chapter. 

Substituted benzenes are obtained from the reaction of carbenes with phosphorins. The phosphepin (123) is thought to be an intermediate because the related compound (124) decomposes to a substituted benzene. 

Using the pseudo-first-order equation A obsd = 0 + co2 [COiKwhere kcoi is the second-order rate constant for the reaction of carbene with CO2 and ko is the rate of carbene decay in the absence of CO2), solution-phase values of kcoi for phenylchlorocarbenes 9 and 12, and diphenylcarbenes 14 and 15 in dichloromethane were estimated (Table 4.1). (The concentration of CO2 in saturated dichloromethane solution at 25°C and 1 atm is 196mmol/L. ) The trend of these estimated second-order order rate constants agrees with that observed in low-temperature matrices by Sander and co-workers. ... 

Since the most direct evidence for specihc solvation of a carbene would be a spectroscopic signature distinct from that of the free carbene and also from that of a fully formed ylide, TRIR spectroscopy has been used to search for such car-bene-solvent interactions. Chlorophenylcarbene (32) and fluorophenylcarbene (33) were recently examined by TRIR spectroscopy in the absence and presence of tetrahydrofuran (THF) or benzene. These carbenes possess IR bands near 1225 cm that largely involve stretching of the partial double bond between the carbene carbon and the aromatic ring. It was anticipated that electron pair donation from a coordinating solvent such as THF or benzene into the empty carbene p-orbital might reduce the partial double bond character to the carbene center, shifting this vibrational frequency to a lower value. However, such shifts were not observed, perhaps because these halophenylcarbenes are so well stabilized that interactions with solvent are too weak to be observed. The bimolecular rate constant for the reaction of carbenes 32 and 33 with tetramethylethylene (TME) was also unaffected by THF or benzene, consistent with the lack of solvent coordination in these cases. °... 

The Reaction of Carbenes with Alkenes in Aqueous Medium... 

The reaction of carbenes or carbenoids with compounds containing S—S bonds is likely to begin with sulfonium ylide formation subsequent [1,2] rearrangement then produces a formal insertion product of the carbene moiety into the S—S bond152 b). 

The reactions of carbenes are of great synthetic use in the preparation of compounds that have three-membered rings. 

The reaction of carbenes with alcohols can proceed by various pathways, which are most readily distinguished if the divalent carbon is conjugated to a tt system (Scheme 5). Both the ylide mechanism (a) and concerted O-H insertion (b) introduce the alkoxy group at the originally divalent site. On the other hand, carbene protonation (c) gives rise to allylic cations, which will accept nucleophiles at C-l and C-3 to give mixtures of isomeric ethers. In the case of R1 = R2, deuterated alcohols will afford mixtures of isotopomers. 

The reaction of carbenes 1, generated either thermally or photochemically from the corresponding quinone diazides 2, with pyridine results in the formation of the deeply colored betaines which can be isolated in substance from the reaction mixture.73,62 This alternative synthesis of the betaines opens a general route to pyridine ylides unsubstituted at the pyridine ring. 

Compared to the parent system 3a, the barrier for formation of 3d is the highest in this series whereas the formation of 3b should be the most facile according to our computations. Although the reactions of carbenes la-c are initiated photochemically, the observed reactivity seems to be in line with the computed ground state properties. Thus, while methyl substitution in 3-and 5-position inhibits the vinylcarbene-cyclopropene rearrangement, methyl substitution in 2- and 6-position has the opposite effect. 

R = Pr) via a bromide displacement process. Halide displacements have been observed previously in the reactions of carbenes with Me3SiI (38). However, this represents the first such reaction with a haloborane. The X-ray crystal structure of 49 was determined and showed that both heterocyclic rings are planar and that the interpla-nar angle is 92.9°. The B-C(carbene) bond distance of 1.580(11) A is comparable to that found in 32 (1.603(3) A). 

The properties of carbenes are also expected to depend very greatly on the electronic characteristics of substituents bound to the divalent carbon. For example, many carbenes with heteroatomic elements attached directly to the central carbon are calculated to have single ground states (Mueller et al., 1981). The early, pioneering work on the stereochemistry of the reaction of carbenes with olefins was done with dibromocarbene (Skell and Garner,... 

The reaction of carbenes with alcohols to form ethers (6) occupies a central and critical position in the network of observations that define the properties... 

Selected examples of the reaction of carbenes with alkyl and arylalkenes R R3C=CR3R4 Reaction conditions % yield... 

The normal byproducts formed during the transition metal-catalyzed decomposition of diazoalkanes are carbene dimers and azines [496,1023,1329], These products result from the reaction of carbene complexes with the carbene precursor. Their formation can be suppressed by slow addition (e.g. with a syringe motor) of a dilute solution of the diazo compound to the mixture of substrate and catalyst. Carbene dimerization can, however, also be a synthetically useful process. If, e.g., diazoacetone is treated with 0.1% RuClCpIPPhjij at 65 °C in toluene, cw-3-hexene-2,5-dione is obtained in 81% yield with high stereoselectivity [1038]. 

The direct assembly of nitrile ylides by the reaction of carbenes (e.g., 84) with nitriles has, in principle, great potential for structural variation as both components are easily accessible. The first reports of such reactions appeared in the early 1980s and were concerned with the reaction of nitriles with stabilized carbenes such as 84 and 86 (41 3). 

Throughout this chapter, we have almost always ignored the role of the carbene precursor. Carbenes are generally made from diazo compounds, or from a variety of surrogate diazo compounds including diazirines, tosylhydrazone salts, and aziridyl imines, all of which probably decompose through nonisolable diazo compounds. Not surprisingly, it turns out that diazo compounds have a rich chemistry of their own, especially when irradiated. Moreover, that chemistry often closely resembles the reactions of carbenes. Much of intramolecular carbene chemistry is, in fact, diazo compound chemistry. 

Take the reaction of carbenes generated by photolysis of diazo compounds (Scheme 9.1), for example. Direct irradiation of a diazo compound (12) is believed to generate the carbene initially in singlet state ( 3) via the singlet excited state of the precursor. Triplet sensization, on the other hand, is presumed to give the triplet... 

TABLE 9.12. Bimolecular Rate Constants for the Reaction of Carbenes (R—C—R ) with Oxygen... 

For a monograph, see Johnson Ylid Chemistry, Academic Press New York. 1966. For reviews, sec Morris. Surv. Prog. Chem. 1983, 10, 189-257 Hudson Chem. Br. 1971, 7, 287-294 Lowe Chem. Ind. (London) 1970, 1070-1079. For a review on the formation of ylides from the reaction of carbenes and carbenoids with heteroatom lone pairs, see Padwa Hornbuckle Chem. Rev. 1991, 91, 263-309. 

By far, the reaction of carbenes is the most important. The 1969 paper by Makosza and Wawrzyniewicz238 described the generation of dichlorocar-... 

In recent years there has been a growing interest in the use of carbonyl ylides as 1,3-dipoles for total synthesis.127-130 Their dipolar cycloaddition to alkenic, alkynic and hetero multiple bonded dipolaro-philes has been well documented.6 Methods for the generation of carbonyl ylides include the thermal and photochemical opening of oxiranes,131 the thermal fragmentation of certain heterocyclic structures such as A3-l,3,4-oxadiazolines (141) or l,3-dioxolan-4-ones132-134 (142) and the reaction of carbenes or car-benoids with carbonyl derivatives.133-138 Formation of a carbonyl ylide by attack of a rhodium carbenoid... 

Deuterium study of the reactions of carbenes with OH bond... 

More attention has been paid to tungsten complexes and Raubenheimer and coworkers502 studied the reactions of carbene complexes such as [W(CO)s C(OEt)Ph) with a variety of electrophiles to give coordinated thioaldehydes. Fischer s group has reported many studies on the behavior of pentacarbonyltungsten-coordinated thiobenzaldehyde [(CO)sW S=C(Ph)H ] with vinyl ethers503 (equation 153) and alkynes504. 

Rate constants have been measured for the capture of para-substituted phenylchloro-carbenes by chloride ions to form aryldichloromethide carbanions and for the additions of these carbanions to acrylonitrile.144 A conventional interpretation of the Hammett correlations has suggested that the reactions of carbenes with Cl- traverse early transition states. 

The reaction of carbenes with appropriately substituted olefins provides a useful method for the preparation of many cyclopropanone derivatives. The Simmons-Smith procedure 22> and reactions involving base-generated carbenes, e.g. CHC13/KO-7-Bu, are particularly useful. 

The reaction of carbene complexes with alkynes offers useful synthetic methods. The formation of various cyclic compounds by the reaction of alkynes with the alkoxycarbene complex 259 can be summarized by the following scheme, which is simplified for easy understanding, although the explanation is not exactly correct mechanistically. 

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