Methyl reaction + carbenes

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... 

Methyllithium (and likewise BuLi and allyllithium) also adds to the carbene ligand of (CO)5W[C(OMe)Ph]. However, the reaction of the resulting anionic adduct with Si02/pentane at —40°C yields pentacarbonyl(n -olefin)-W complexes, probably via the intermediary formation of the methyl(phenyl)carbene complex and following rearrangement via 1,2-hydrogen shift ... 

Chang and Chu (ref. 1) added propane (3 moles) to converting methanol and found that the yield ratio of i-butane to n-butane, i/n, changed from 3.8 to 1.1 on this addition. Helium was used instead of propane in the control run. They argue that carbene methylates by an insertion reaction in which it attacks C-H links at random so that propane, having 6 primary C-H links and 2 secondary C-H links, should yield i/n = 2/6 or 1/3. The fact that i/n falls on addition of propane is then due to methylation by carbene. 

This section only covers [2+ l]-cycloaddition reactions performed with carbenes. The synthesis of trifiuoromethyl-substituted three-membered-ring compounds has been achieved by reaction of carbenes with trifluoromethyl-subsliluled unsaturated systems and by reaction of trifluoro-methyl-substituted carbenes with alkenes. 

H-Pyran, 2-alkoxy-4-methyl-2,3-dihydro-conformation, 3, 630 4H-Pyran, 2-amino-IR spectra, 3, 593 synthesis, 3, 758 4H-Pyran, 4-benzylidene-synthesis, 3, 762 4H-Pyran, 2,3-dihydro-halogenation, 3, 723 hydroboration, 3, 723 oxepines from, 3, 725 oxidation, 3, 724 reactions, with acids, 3, 723 with carbenes, 3, 725 4H-Pyran, 5,6-dihydro-synthesis, 2, 91 4H-Pyran, 2,6-diphenyl-hydrogenation, 3, 777 4H-Pyran, 6-ethyl-3-vinyl-2,3-dihydro-reactions, with acids, 3, 723 4H-Pyran, 2-methoxy-synthesis, 3, 762 4H-Pyran, 2,4,4,6-tetramethyl-IR spectra, 3, 593 4H-Pyran, 2,4,6-triphenyl-IR spectra, 3, 593... 

Deprotonation of l-methyl-3-ferrocenylimidazolium tetrafluoroborate or iodide (98JOM(552)45) by lithium di-Mo-propylamide and subsequent reaction with W(C0)5-THF gives the carbene complex 107 and bis-carbene 108, even when excess W(CO)j THF is applied (99JOM(572)177). Numerous ferrocenyl benzimidazoles are known (97RCR613, 99JOM(580)26). 

Lithium 4-methylthiazolate and benzothiazolate with [( / -Cp)Fe(CO)2Cl] form the C-coordinated complexes, e.g. 23, which on protonation with triflic acid transform into the carbenes, e.g. 24 (92JCS(D)1009). Isothiazole enters the same chain of reactions but can also be methylated using methyl triflate (94JOM(479)C12). 

In pyridinium chloride ionic liquids and in l,2-dimethyl-3-hexylimida2olium chloride ([HMMIMjCl), where the C(2) position is protected by a methyl group, only [PdClJ was observed, whereas in [HMIMjCl, the EXAFS showed the formation of a bis-carbene complex. In the presence of triphenylphosphine, Pd-P coordination was observed in all ionic liquids except where the carbene complex was formed. During the Heck reaction, the formation of palladium was found to be quicker than in the absence of reagents. Overall, the EXAFS showed the presence of small palladium clusters of approximately 1 nm diameter formed in solution. 

The addition of carbene to a 3-(halopropyl)-5//-dibenz[7>./]azepine 5 (X = Cl, Br) in a Simmons—Smith reaction is more complex and results in a mixture of the tetracycle 6 (6%), its cyclopropano derivative 7 (48 %), the 5-allyl derivative 8 and the (cyclopropyl)methyl compound 9, the latter two products in a combined yield of 12%.31... 

The reaction of alkoxyarylcarbene complexes with alkynes mainly affords Dotz benzannulated [3C+2S+1C0] cycloadducts. However, uncommon reaction pathways of some alkoxyarylcarbene complexes in their reaction with alkynes leading to indene derivatives in a formal [3C+2S] cycloaddition process have been reported. For example, the reaction of methoxy(2,6-dimethylphenyl)chromium carbene complex with 1,2-diphenylacetylene at 100 °C gives rise to an unusual indene derivative where a sigmatropic 1,5-methyl shift is observed [60]. Moreover, a related (4-hydroxy-2,6-dimethylphenyl)carbene complex reacts in benzene at 100 °C with 3-hexyne to produce an indene derivative. However, the expected Dotz cycloadduct is obtained when the solvent is changed to acetonitrile [61] (Scheme 19). Also, Dotz et al. have shown that the introduction of an isocyanide ligand into the coordination sphere of the metal induces the preferential formation of indene derivatives [62]. 

Carbene complexes which have an all-carbon tether between the diene and the dienophile react via intramolecular Diels-Alder reaction to give the corresponding bicyclic compound. The stereoselectivities of these reactions are comparable to those observed for the Lewis acid-catalysed reactions of the corresponding methyl esters and much higher than those of the thermal reactions of the methyl esters which are completely unselective. Moreover, the ris-sub-stituted complexes undergo endo-selective reactions where the corresponding reaction of the ester fails [109] (Scheme 61). 

Seven-membered carbocycles are also available from the reaction of alkenylcarbene complexes of chromium and lithium enolates derived from methyl vinyl ketones [79b] (Scheme 65). In this case, the reaction is initiated by the 1,2-addition of the enolate to the carbene complex. Cyclisation induced by a [1,2]-migration of the pentacarbonylchromium group and subsequent elimination of the metal fragment followed by hydrolysis leads to the final cyclo-heptenone derivatives (Scheme 65). 

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. 

Other examples of [2C+2S+1C0] cycloaddition reactions have been described by Herndon et al. by the use of chromium cyclopropyl(methoxy)carbenes. These complexes react with alkynes releasing ethene and forming cyclopenta-dienone derivatives, which evolve to cyclopentenone derivatives in the presence of chromium(O) and water [122] (Scheme 76). This reaction has been extended to intramolecular processes and also to the synthesis of some natural products [123]. These authors have also described another process involving a formal [2C+2S+1C0] cycloaddition reaction. Thus, the reaction of methyl and cyclo-propylcarbene complexes with phenylacetylene derivatives does not afford the expected benzannulated products, and several regioisomers of cyclopentenone derivatives are the only products isolated [124] (Scheme 76). 

The reaction in which aldehydes are converted to methyl ketones, RCHO -f CH2N2 —> RCOCH3, while apparently similar, does not involve a free carbene intermediate. It is considered in Chapter 18 (18-9). 

As the phosphonium diylides, lithium phosphonium yldiides, first described by Schlosser and Corey (Ph3P=CR-Li R=H, C3H7) [60-62], have a high nucleophilicity and reactivity. Recently, the a-silylated lithium phosphonium yldiide 20 has been prepared from the stable phosphanyl-(silyl)carbene 19 and alkyl-lithium (Scheme 13). The first crystal X-ray diffraction study of such a reagent was proposed for 20 and its reaction with methyl iodide or phosphorus elec-... 

Aryldiazomethane can also be used for iron porphyrin-catalyzed alkene cyclopropanation [55]. For example, the treatment of p-tolyldiazomethane with styrene in the presence of [Fe(TTP)] afforded the corresponding arylcyclopropapane in 79% yield with a high transicis ratio of 14 1 (eq. 1 in Scheme 11). Interestingly, when bulkier mesityldiazomethane was used as carbene source, ds-selectivity was observed (cisitrans = 2.0 1). Additionally, mesityldiazomethane was found to react with frans-p-styrene, the latter was found not to react with EDA or trimethyl-silyldiazomethane under the similar reaction conditions, to give l-mesityl-2-methyl-3-phenylcyclopropane in 35% yield. Trimethylsilyldiazomethane is also an active carbene source for [Fe(TTP)]-catalyzed cyclopropanation of styrene, affording l-phenyl-2-trimethylsilylcyclopropane in 89% yield with transicis ratio of 10 1 (eq. 2 in Scheme 11). 

Vinyl cyclopropanes tethered to an aUcyne chain 127 were also subjected to the cycloisomerisation reaction in presence of the NHC-Ni catalyst system (Scheme 5.34) [39], The product formation depends on the substrate used and the NHC hgand. When SIPr carbene is used, three different products were obtained depending on the size of the R group attached to the alkyne moiety. If R is small (like a methyl) product 128 is obtained exclusively. If R is Et or Pr a mixture of 128 and 129 is obtained in 3 2 to 1 2 ratio, respectively. However, when R is large groups such as Bu or TMS only product 130 is obtained. When IfBu carbene 131 is used as the ligand, cycloisomerisation of 127 afforded product 128 exclusively, regardless of substituent size (Scheme 5.34) [39]. 

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