Carbenes alkoxy

The ability of Fischer carbene complexes to transfer their carbene ligand to an electron-deficient olefin was discovered by Fischer and Dotz in 1970 [5]. Further studies have demonstrated the generality of this thermal process, which occurs between (alkyl)-, (aryl)-, and (alkenyl)(alkoxy)carbene complexes and different electron-withdrawing substituted alkenes [6] (Scheme 1). For certain substrates, a common side reaction in these processes is the insertion of the carbene ligand into an olefinic C-H bond [6, 7]. In addition, it has been ob-... 

Asymmetric versions of the cyclopropanation reaction of electron-deficient olefins using chirally modified Fischer carbene complexes, prepared by exchange of CO ligands with chiral bisphosphites [21a] or phosphines [21b], have been tested. However, the asymmetric inductions are rather modest [21a] or not quantified (only the observation that the cyclopropane is optically active is reported) [21b]. Much better facial selectivities are reached in the cyclopropanation of enantiopure alkenyl oxazolines with aryl- or alkyl-substituted alkoxy-carbene complexes of chromium [22] (Scheme 5). 

Alkoxy(carbene)iron(0) and amino(carbene)iron(0) complexes usually react with alkynes to give rj4-pyrone iron complexes and furans, respectively [54]. Nevertheless the chemoselective formation of naphthols was reported for alkoxy(carbene)iron(0) complexes with the electron-poor alkyne dimethyl... 

Sulfur-stabilized ylides underwent photodriven reaction with chromium alkoxy-carbenes to produce 2-acyl vinyl ethers as E/Z mixtures with the E isomer predominating (Table 22) [ 121-123]. The reaction is thought to proceed by nucleophilic attack of the ylide carbon at the chromium carbene carbon followed by elimination of (CO)5CrSMe2. The same reaction occurred thermally, but at a reduced rate. Sulfilimines underwent a similar addition/elimination process to produce imidates or their hydrolysis products (Table 23) [ 124,125]. Again the reaction also proceeded thermally but much more slowly. Less basic sulfilimines having acyl or sulfonyl groups on nitrogen failed to react. 

An indirect carbonylation of aldehydes via photolysis of chromium alkoxy-carbenes with aldehydes in the presence of Lewis acids was reported by Hegedus [66]. The formation of /1-lactones was especially efficient when the aldehyde was incorporated into either chain of the carbene ligand resulting in an intramolecular process. 

The thermal reaction of vinyl- or aryl(alkoxy)carbene chromium complexes with alkynes can give high yields of 4-alkoxyphenols (Figure 2.24). This elegant synthetic procedure was reported for the first time by Dotz in 1975 [326] and has proven robust and of broad scope. 

Arene(alkoxy)carbene chromium complexes react with aryl-, alkyl-, terminal, or internal alkynes in ethers or acetonitrile to yield 4-alkoxy-1-naphthols, with the sterically more demanding substituent of the alkyne (Rl Figure 2.24) ortho to the hydroxy group. Acceptor-substituted alkynes can also be used in this reaction (Entry 4, Table 2.17) [331]. Donor-substituted alkynes can however lead to the formation of other products [191,192]. Also (diarylcarbene)pentacarbonyl chromium complexes can react with alkynes to yield phenols [332]. 

The intermediate vinylketene complexes can undergo several other types or reaction, depending primarily on the substitution pattern, the metal and the solvent used (Figure 2.27). More than 15 different types of product have been obtained from the reaction of aryl(alkoxy)carbene chromium complexes with alkynes [333,334]. In addition to the formation of indenes [337], some arylcarbene complexes yield cyclobutenones [338], lactones, or furans [91] (e.g. Entry 4, Table 2.19) upon reaction with alkynes. Cyclobutenones can also be obtained by reaction of alkoxy(alkyl)carbene complexes with alkynes [339]. 

On the contrary, a-lithiated epoxides have found wide application in syntheses . The existence of this type of intermediate as well as its carbenoid character became obvious from a transannular reaction of cyclooctene oxide 89 observed by Cope and coworkers. Thus, deuterium-labeling studies revealed that the lithiated epoxide 90 is formed upon treatment of the oxirane 89 with bases like lithium diethylamide. Then, a transannular C—H insertion occurs and the bicyclic carbinol 92 forms after protonation (equation 51). This result can be interpreted as a C—H insertion reaction of the lithium carbenoid 90 itself. On the other hand, this transformation could proceed via the a-alkoxy carbene 91. In both cases, the release of strain due to the opening of the oxirane ring is a significant driving force of the reaction. 

Concerning the possible rearrangement of the lithiooxirane into the alkoxy carbene 155, calculations have also shown that the activation energies of the 1,2-H shifts (to cyclopentanone enolate or cyclopentenol) are extremely high (at least 23 kcalmol" ) from 155, whereas they are much lower (between —0.4 kcalmol" and 8.8 kcalmol" ) from carbene 154. This is explained by a strong intramolecular stabilization of the carbene by the alcoholate moiety, as depicted in Scheme 66. This stabilization could signify that the formation of a carbene from the carbenoid is a disfavored process, and that the carbenoid itself is involved in the rearrangement reaction. 

In 1986, Kesselmayer and Sheridan reported the matrix isolation and IR spectrum of chloro-methoxymethylene. They were able to show that two isomeric forms were present, trans (12) and cis (13). This is in line with Schaefer s " finding that hydroxymethylene should exist in cis- and frons-forms. While Kesselmayer and Sheridan were able to assign several of the bands in the matrix mixture to the cis- and trans-forms, they were unable to assign the majority of the bands in the IR spectrum they obtained to the specific isomer. In order to further confirm their isolation of these alkoxy carbenes, as well as to help in the interpretation of the observed IR spectrum, we undertook the calculation of the IR spectra of 12 and 13. ... 

Reactions with alcohols proceed similarly, but as the products cannot eliminate any fragment, formation of alkoxy-carbenes is observed (Equation 1.14) ... 

Alkoxy carbene complexes are useful starting compounds for other organometallic complexes,1 5 particularly methylidyne (carbyne) complexes.16 By modification of the coordinated (noncarbene) ligands or of the carbene ligand, other carbene complexes can be synthesized. The use of carbene complexes in organic syntheses has been reviewed recently.17 18... 

Photolysis of pentacarbonylcarbenechromium complexes produce species that react as if they were ketenes. although no evidence for the generation of free ketenes has been observed. Indeed, photolysis of chromium (alkoxy) carbenes in the presence of a range of simple alkenes produced cyclobutanones 1 in good to very good yield.8,9... 

Epoxides such as 10 can be prepared in high enantiomeric purity, by, inter alia, kinetic resolution. David Hodgson of Oxford University has demonstrated (J. Am. Chem. Soc. 2004, /26,8664) that on exposure to LTMP, monosubstituted epoxides are smoothly converted into the corresponding alkoxy carbenc or alkoxy carbenoid. When an alkene is available for insertion, the cyclopropane, in this case 11, is formed with high diastereocontrol. This represents a powerful new approach to enantioselective ring construction. It is possible that in the absence of a target alkene, the intermediate alkoxy carbene could divert to intramolecular C-H insertion, which might also proceed with substantial diastereocontrol. 

In this regard, it is noteworthy that while surface bound hydroxycarbenes are postulated species, discrete complexes containing hydroxy- and alkoxy-carbenes have been known since E. O. Fischer s studies beginning in 1964 (56, 57). These complexes are possibly analogous to proposed surface intermediates, and their chemistry may model some of the heterogeneously catalyzed transformations. Coupling of alkoxy carbenes, for example, gives dialkoxy olefins as observed in (20). 

A variation on Scheme 27 and Equation (19) has been utilized by Keeffe and the author to evaluate p fas of alkyl, aryl and alkoxy carbenes.26 For carboca-tions for which the pKA for loss of a proton from a (3-carbon atom is known, combination of this pKA with the experimental or calculated energy difference between alkene and carbene conjugate bases leads to the pAa for protonation of the carbene, provided it can be assumed that the energy difference between alkene and carbene is insensitive to solvent. Where a pKA for loss of a (3-hydrogen of the carbocation is not accessible, for example, for carbenes lacking a (3-hydrogen, p fR can be used instead. Thus the cycle of Scheme 28 relates a pKa for protonation of the carbene to an experimentally measured... 

Enantiopure alkynyl(alkoxy)carbene (37) complexes were produced by formal alkyne insertion into Fisher carbene complexes 39 Reaction of (37) with 1-azadiene gave functionalized 1,4-dihydropyridine (38) with high enantiomeric excess. 

Alkylation,4 Alkylation of anions of the usual alkoxy carbene complexes is not generally attractive because of low reactivity. However, the anion of dialkylamino chromium carbenes such as 1 (R = H) can be alkylated readily and in a useful yield. 

Replacing the alkoxy carbene substituent by a better electron-donating amino group stabilizes the metal carbonyl bond. As a result, CO insertion in vinyl carbene D is hampered instead, cyclopentannulation via the chromacyclohexadiene I leads to aminoindenes K, which are readily hydrolyzed to indanones L (Scheme 6) [20]. 

Scheme 9. Chiral alkoxy carbene complexes from the alcoholysis of acyloxy carbene complexes.

Although mostly alkoxy carbene complexes have been benzannulated, other types of carbene complexes are equally well suited. These include aryloxy carbene complexes as well as acyla-mino and thioalkylidene complexes, and even complexes with no heteroatoms, such as diaryl carbene complexes, are suitable (see below). Besides the commonly used methoxy and ethoxy carbene complexes, alkoxy carbene complexes with a longer alkyl chain have also been successfully reacted. The benzannulation of aryloxy carbene complexes has recently been studied to probe electronic effects [28a]. Aryloxy alkylidene complexes of type 21 have been used to prepare diaryl ethers 22, which constitute a common substructure in many important types of natural products [28b]. The benzannulation methodology provides an access to phenyl naphthyl ethers in yields of 60-93 % under mild conditions (Scheme 11). 

Arnold and co-workers also reported the deprotonation of alkoxy imi-dazolium iodides with -butyl lithium to yield lithium alkoxide carbenes (Scheme 3).14 Single crystals of one of the complexes were grown from a diethyl ether solution, and revealed a dimer of LiL with lithium iodide incorporated to form a tetramer of lithium cations (7). The lithium-NHC bond distance of 2.131(6) A is similar to that of the lithium amide carbene 4. Also as in 4 there is distortion of the lithium-NCN bond which has an angle of 152.3°. The C2 carbon resonates at 200 ppm in the 13C NMR spectrum which is a relatively high-frequency, possibly as a result of the incorporated lithium iodide. The lithium salts were able to act as ligand transfer reagents and react with copper (II) chloride or triflate to afford mono- or bis-substituted copper(II) alkoxy carbene complexes. 

When a bulky bis(adamantylethoxy) imidazolium salt was treated with potassium hydride the reaction did not afford the expected potassium-carbene.18 Instead, elimination of one alcohol arm produced a mono (adamantylethoxy) imidazole (9) (Scheme 5). Treatment of this with isopropyl iodide resulted in the alcohol imidazolium iodide salt, which undergoes deprotonation with lithium hexamethyldisilazide to afford the lithium alkoxy carbene (10) which was characterised by mass spectrometry and multinuclear NMR spectroscopy. The C2 carbon in 10 resonates at 186.3 ppm in the 13C NMR spectrum, which is a significantly lower frequency than the similar ligand in 7 which has lithium iodide incorporated into the structure. 

Hydrazinolysis of (alkoxy)carbene complexes (CO)5M = C(OEt)R (M = Cr, Mo, W) has been studied much less than the aminolysis of such compounds.149"152 Usually, hydrazinolysis takes a nonuniform course and yields several seemingly different products. The preparation of (hydrazino)-... 

C(OMe) —CH3 with an ortho ester 175 (iii) the condensation of aryl- or alkylcarbene complexes with enolizable acid amides RCH2 —CONR2, a reaction involving insertion of the C—CN unit of the acid amide into the M=C bond 176 (iv) the insertion of an alkyne into the M=C bond of an (alkoxy)carbene complex 36,177 174 and (v) the base-catalyzed addition of an alcohol to a (l-alkynyl)carbene complex.96 168173 The last reaction has... 

Hydride abstraction in alkoxyalkyl complexes to the corresponding alkoxy carbene complex has also been shown (Equation (17)) [50]. 

Irradiation of alkoxycarbene complexes in the presence of aUcenes and carbon monoxide produces cyclobutanones. A variety of inter- and intramolecular [2 + 2]cycloadditions have been reported. The regioselectivity is comparable with those obtained in reactions of ketenes generated from carboxylic acid derivatives. Cyclobutanones can be obtained with a high degree of diastereoselectivity upon reaction of alkoxy carbenes with chiral A-vinyloxazolidinones. For example, photolysis of (19) in the presence of (20) gives cyclobutanone (21) (Scheme 31). In addition to aUcoxycarbenes, carbenes having a thioether or pyrrole substituent can also be employed. Related intramolecular cycloadditions of y,5-unsaturated chromimn carbenes afford bicyclo[2.1. IJhexanones (Scheme 32). 

Diastereoselective and enantioselective (see Enantio-selectivity) cyclopropanations of chiral alkenes can be achieved (Scheme 57). Unactivated alkenes usually do not participate in cyclopropanation reactions of Fischer carbenes. However, alkenyl- and heteroaryl-substituted group 6 alkoxy carbene complexes cyclopropanate unactivated alkenes in good yield (Scheme 58). ... 

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