Carbene with alcohols

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

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 reactivities of carbenes toward alkenes have been correlated with the inductive and resonance effects of the carbene substituents, log k — a Eat + fcEaR+ + c.m Analogous correlations cannot be obtained for the reaction rates of carbenes with alcohols, neither with the substituent parameters used by Moss,109 nor with related sets.110 In particular, the substituent parameters do not describe the strong, rate-enhancing effect of aryl groups. For a detailed analysis, see the discussion of proton affinities (Section V.A). 

The reaction of singlet carbenes with alcohols has been studied by PAC and the results have led to some interesting mechanistic implications 41,42 The rates, kr, and heats of reaction, A HT, of the singlet carbenes with methanol vary with substitution (Fig. 3).53... 

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... 

The reaction patterns of arylcarbenes with solidified alcohol at 77 K are also completely different from those observed in alcohol solution. For example, generation of phenylcarbene (le) in methanol matrices at 77 K results in the formation of alcohol (63) at the expense of benzyl methyl ether (62), which is the exclusive product in the reaction in alcoholic solution at ambient temperatures (Scheme 9.14). A similar dramatic increase in the CH insertion products is observed in the reaction involving other carbenes with alcohols. ... 

Figure 7.41 Mechanisms of reaction of glycosylidene carbenes with alcohols.

These ideas fit very well to our discussion in Section 8.3, where we showed that carbenes may react predominantly via the HOMO or via the LUMO, or, in other words, that the opposite signs of the resonance and field effects of carbene substituents and of the substrate lead to correlations of reactivities that cannot be explained by a standard combination of resonance and field effects. One hopes that, some time in the future, there will be a sufficient number of strictly comparable rate coefficients of carbenes with alcohols to evaluate them with a dual substituent parameter system, as we have done for cyclopropanations with substituted carbenes (Zollinger, 1990). 

The use of sodium tribromoacetate as the dibromocarbene precursor has been investigated and found to provide the Ciamician-Dennstedt product in higher yield than the traditional alkoxide/alcohol reaction conditions. Deprotonation of bromoform with sodium ethoxide in ethanol and reaction of the resultant carbene with 6 provides quinoline 9 in 9% yield thermolysis of sodium tribromoacetate in the presence of 6 furnishes 9 in 20% yield (Scheme 8.3.3). 

Diazoalkanes can also be converted to ethers by thermal or photochemical cleavage in the presence of an alcohol. These are carbene or carbenoid reactions. Similar intermediates are involved when diazoalkanes react with alcohols in the presence of /-BuOCl to give acetals. ... 

This key paper was followed by a flurry of activity in this area, spanning several years." " "" A variety of workers reported attempts to deconvolute the temperature dependence of carbene singlet/triplet equilibria and relative reactivities from the influence of solid matrices. Invariably, in low-temperature solids, H-abstraction reactions were found to predominate over other processes. Somewhat similar results were obtained in studies of the temperature and phase dependency of the selectivity of C-H insertion reactions in alkanes. While, for example, primary versus tertiary C-H abstraction became increasingly selective as the temperature was lowered in solution, the reactions became dramatically less selective in the solid phase as temperatures were lowered further. Similar work of Tomioka and co-workers explored variations of OH (singlet reaction) versus C-H (triplet reaction) carbene insertions with alcohols as a function of temperature and medium. Numerous attempts were made in these reports to explain the results based on increases in triplet carbene population... 

Photolysis of acyldisilanes at A > 360 nm (103,104) was shown, based on trapping experiments, to yield both silenes 22 and the isomeric siloxy-carbenes 23, but with polysilylacylsilanes only silenes 24 are formed, as shown by trapping experiments and NMR spectroscopy (104,122-124) (see Scheme 4). These silenes react conventionally with alcohols, 2,3-dimethylbutadiene (with one or two giving some evidence of minor amounts of ene-like products), and in a [2 + 2] manner with phenyl-propyne. Ketones, however, do not react cleanly. Perhaps the most unusual behavior of this family of silenes is their exclusive head-to-head dimerization as described in Section V. More recently it has been found that these silenes undergo thermal [2 + 2] reactions with butadiene itself (with minor amounts of the [2 + 4] adduct) and with styrene and vinyl-naphthalene. Also, it has been found that a dimethylsilylene precursor will... 

Aryl(trimethylsiloxy)carbenes. Acylsilanes (153) undergo a photoinduced C —> O silyl shift leading to aryl(trimethylsiloxy)carbenes (154).73,74 The carbenes 154 can be captured by alcohols to form acetals (157) 73 or by pyridine to give transient ylides (Scheme 29).75 LFP of 153 in TFE produced transient absorptions of the carbocations 155 which were characterized by their reactions with nucleophiles.76 The cations 155 are more reactive than ArPhCH+, but only by factors < 10. Comparison of 154 and 155 with Ar(RO)C and Ar(RO)CH+, respectively, would be of interest. Although LFP was applied to generate methoxy(phenyl)carbene and to monitor its reaction with alcohols,77 no attempt was made to detect the analogous carbocation. 

If the reaction rates of a specific carbene with various quenchers are studied in the same solvent, and with small concentrations of Q, K will be constant. Relative reactivities for the singlet state of a spin-equilibrated carbene can thus be derived. However, few researchers have varied the acidity of ROH, estimated kinetic isotope effects, and compared alcohols with ethers (Table 4). The data indicate proton transfer to diarylcarbenes (139d, 139k, 205, 206)112-117 and diadamantylcarbene (207).118... 

The pyridine ylide method also allows determination of the rate constants for the intermolecular reactions of carbenes with alkenes, alcohols, or other carbene... 

The absorption spectrum measured in the typical pump-probe experiment is the difference between the spectrum of the remaining irradiated precursor and the created intermediate(s). Assignment of the transient absorption spectrum typically is done by reference to the low-temperature spectra described above, and (sometimes more certainly) by analysing the chemical behavior of the intermediate. For example, many carbenes are known to react with alcohols to give ethers (see below). If the detected intermediate can be observed to react with an alcohol, then this is taken as additional evidence for its assignment as a carbene. 

The second route for ether formation is initiated by protonation of the carbene followed by capture of the cation with alcohol (8). Finally a concerted insertion into the oxygen-hydrogen bond of the alcohol (8) has been considered, but there is no experimental support for this path. The... 

Whichever mechanism operates, it appears to be generally true that singlet aromatic carbenes react with the lower alcohols to form ethers at rates approaching the diffusion limit. On the other hand, aromatic carbenes that are clearly triplets do not give any ether at all from reaction with alcohols. Instead, these triplets behave as is expected of biradicals and abstract a hydrogen atom from the oxygen bearing carbon of the alcohol. The stable products of this reaction are those due to the combination and disproportionation (10) of the pair of radicals (Lapin et al., 1984). The more com-... 

AGst for BA, XA and DMFL are limits based on unobserved reactions for the other carbenes AGST is calculated by assuming a diffusion controlled reaction rate for the singlet carbene with methyl alcohol. All kinetic parameters refer to room temperature k Sitzmann and Eisenthal, 1983... 

Laser spectroscopic study of the reaction of FL with alcohols in either acetonitrile or hydrocarbon solution appears to show that 3FL is consumed rapidly by the alcohol the absorptions associated with 3FL decay faster in the presence of alcohol than in its absence. However, the product of this reaction is the ether expected from the singlet carbene (Table 7). Moreover,... 

A value for AGSX for FL can be obtained from analysis of the rate of reaction of the carbene with methyl alcohol within the spin-specific reaction framework identified above. Basically, the observed rate of reaction of 3FL with the alcohol is a measure of the amount of XFL in the equilibrium mixture. This gives (28) which links Kemeasured rate constant. The equilibrium constant in turn gives AGSX and, when combined with the picosecond spectroscopic results, and kTS (Table 8). 

Photolysis of DMDAF in benzene containing methyl alcohol gives the ether expected from the reaction of the singlet carbene. Monitoring this reaction by laser spectroscopy reveals that the detected transient reacts with the alcohol with a bimolecular rate constant very near the diffusion limits. In contrast, the transient reacts with triethylamine at least 100 times more slowly than it does with alcohol (Table 7). This behavior is inconsistent with identification of the transient as the cation or radical and points to its assignment as the singlet carbene. 

The chemical properties of DPM have been probed with each of the procedures identified earlier. This carbene is known to react with alcohols to give ethers (Kirmse, 1963 Bethell et al., 1965), it adds to olefins non-stereospecifically to form cyclopropanes (Skell, 1959 Baron et al., 1973 Gaspar et al., 1980 Tomioka et al., 1984), and it is rapidly converted to a carbonyl oxide with oxygen (Werstiuk et al., 1984 Casal et al., 1984). 

Etherification using a metal vinylidene has also been combined with G-G bond formation through the reaction of an alkynyl tungsten complex with benzaldehyde (Scheme 14). The addition of an internal alcohol to the incipient /3,/Udialkylvinylidene that is generated leads to dehydration and the formation of a Fischer-type alkylidene complex. Further reactions of this carbene with a range of nucleophiles have provided access to various furan derivatives.374,375... 

Selected examples of the reaction of carbenes with allylic alcohols... 

The catalytic activity of rhodium diacetate compounds in the decomposition of diazo compounds was discovered by Teyssie in 1973 [12] for a reaction of ethyl diazoacetate with water, alcohols, and weak acids to give the carbene inserted alcohol, ether, or ester product. This was soon followed by cyclopropanation. Rhodium(II) acetates form stable dimeric complexes containing four bridging carboxylates and a rhodium-rhodium bond (Figure 17.8). 

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