Carbene-alcohol ylide

The mechanism of 0-H bond insertion by carbenes remains an intense held of investigation. In the case of ether formation, three distinct pathways can be proposed (i) abstraction of protons from the alcohol forming an intermediate ion pair, (ii) reaction with the oxygen atom of an alcohol forming an intermediate ylide, and (hi) direct (concerted) insertion into the O-H bond. In that context, the carbene - alcohol ylide resulting from the reaction between carboethoxycarbene and MeOD has been experimentally detected for the first time, thus corroborating the viability of the ylide pathway. ... 

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. 

Alkenes are scavengers that are able to differentiate between carbenes (cycloaddition) and carbocations (electrophilic addition). The reactions of phenyl-carbene (117) with equimolar mixtures of methanol and alkenes afforded phenylcyclopropanes (120) and benzyl methyl ether (121) as the major products (Scheme 24).51 Electrophilic addition of the benzyl cation (118) to alkenes, leading to 122 and 123 by way of 119, was a minor route (ca. 6%). Isobutene and enol ethers gave similar results. The overall contribution of 118 must be more than 6% as (part of) the ether 121 also originates from 118. Alcohols and enol ethers react with diarylcarbenium ions at about the same rates (ca. 109 M-1 s-1), somewhat faster than alkenes (ca. 108 M-1 s-1).52 By extrapolation, diffusion-controlled rates and indiscriminate reactions are expected for the free (solvated) benzyl cation (118). In support of this notion, the product distributions in Scheme 24 only respond slightly to the nature of the n bond (alkene vs. enol ether). The formation of free benzyl cations from phenylcarbene and methanol is thus estimated to be in the range of 10-15%. However, the major route to the benzyl ether 121, whether by ion-pair collapse or by way of an ylide, cannot be identified. 

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. 

Spectroscopically invisible carbenes can be monitored by the ylide method .92 Here, the carbene reacts with a nucleophile Y to form a strongly absorbing and long-lived ylide, competitively with all other routes of decay. Although pyridine (Py) stands out as the most popular probe, nitriles and thiones have also been used. In the presence of an additional quencher, the observed pseudo-first-order rate constant for ylide formation is given by Eq. 2.92,93 A plot of obs vs. [Q] at constant [Y ] will provide kq. With Q = HX, complications can arise from protonation of Y and/or the derived ylides. The available data indicate that alcohols are compatible with the pyridine-ylide probe technique. 

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

Electrophilic carbene complexes can react with amines, alcohols or thiols to yield the products of a formal X-H bond insertion (X N, O, S). Unlike the insertion of carbene complexes into aliphatic C-H bonds, insertion into X-H bonds can proceed via intermediate formation of ylides (Figure 4.7). 

A number of minima corresponding to oxonium ylides and H-bonded structures were found on the potential-energy surface for reaction of singlet carbenes with water and alcohols." Laser flash photolysis revealed that the rates of reaction between cyclopentadienylidene or fluorenylidene and alcohols increased with alcohol acidity and had linear Bronsted plots with slopes of 0.061 and 0.082, respectively.100 These results point to protonation with a very early transition state or to concerted OH insertion. For tetrachlorocyclopentadienylidene, the results showed that ylide formation (100) is predominant. 

Phenyl(triphenylsilyl)carbene has also been trapped without the interference of a silylcarbene-to-silene rearrangement84. It undergoes 0,H insertion with alcohols and is oxidized to the ketone by DMSO the latter reaction is likely to include an S-oxide ylide (equation 56). 

Asymmetric epoxidation The catalytic asymmetric epoxidation of alkenes has been the focus of many research efforts over the past two decades. The non-racemic epoxides are prepared either by enantioselective oxidation of a prochiral carbon-carbon double bond or by enantioselective alkylidenation of a prochiral C=0 bond (e.g. via a ylide, carbene or the Darzen reaction). The Sharpless asymmetric epoxidation (SAE) requires allylic alcohols. The Jacobsen epoxidation (using manganese-salen complex and NaOCl) works well with ds-alkenes and dioxirane method is good for some trans-alkenes (see Chapter 1, section 1.5.3). 

As mentioned in Section 8.1, carbenes easily undergo insertion into O-H bonds. At an early date, Kerr et al. (1967) found that in the photolysis of diazomethane- er butanol mixtures insertion is eleven times faster at O - H than at C - H bonds. The relative rates of ether formation for methanol, ethanol, 2-propanol, and tert-butanol are 2.01 1.95 1.37 1.00. Before that investigation, Kirmse (1963) postulated that diphenylcarbene is protonated to form the diphenylmethyl carbocation, which, as a strong electrophile, adds to the alcoholate anion (or to the alcohol followed by deprotonation) forming the ether (8-26 a). Bethell et al. (1969, 1971), however, favored an electrophilic attack of diphenylcarbene at the O-atom, i. e., an ylide intermediate on the basis of isotope effects (8-26 b). Finally, a concerted process via the transition state 8.39 may be feasible (8-26 c). 

Looking for the catalytic systems, which may be easily deactivated and removed from the polymer, other nonionic base/alcohol-iiutiating systems have been examined. Phosphoms ylides, R3P = CMe2 (eqn [19]), show the activity similar to phosphazene bases in polymerization of D4. They are thermolabile and easy to remove from the polymer. Promising initiators are also stable (N-hetaryl)carbenes (eqn [20]) and guanidine derivatives. The MWs of the silicone polymers in case of carbenes can be regulated simply by varying the quantity of the alcohol co-initiator. 

Rhodium(II) carbenoid intermediates are also useful. For example, carbene transfer reaction with allylic sulfides followed by [2,3]-sigmatropic rearrangement of the resulting sulfur ylides (Doyle-Kirmse reaction) gives furan-containing sulfides 133 in good yields (Scheme 19.32) [50]. In contrast, reaction with allylic compounds (R—H) or alcohols/amines/thiols/silanes (X—H) furnishes the 1,1-insertion products 134 or 135, respectively [51],... 

Heteroatom Wittig chemistry also includes reactions of N-sulfonyl imines. It was demostrated that these compounds underwent olefination reactions with nonstabilized phosphonium ylides under mild conditions to afford an array of both Z- and E-isomers of 1,2-disubstituted alkenes, allylic alcohols, and allylic amines.Additionally, studies of the reactions of 5-bromo-4,6-dimethyl-2-thioxo-l,2-dihydropyridine-3-carboni-trile and thiazolidinone with phosphorus ylides have proved the formation of new phosphonium ylides. Annulations via P-ylides are a common occurrence in the literature. For example, on photochemical irradiation, phosphonium-iodonium ylides were shown to undergo 1,3-dipolar cycloaddition reactions with triple bonds, via a carbene intermediate, to yield furans. " Even more common are the reactions of Morita-Baylis-Hillman (MBH) acetates and carbonates. Zhou et al. demostrated that these substrates were able to generate very reactive 1,3-dipoles in the presence of tertiary phosphines the dipoles then underwent cycloaddition reactions to yield annulation products (Scheme 16). ... 

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