Vinylidene carbenoids

The particular substitution pattern of lithium carbenoids, the fact that both an electropositive metal and an electronegative substituent X are bound to the same carbon atom, causes the ambiphilic character of this species. The chameleon-like reactivity becomes evident from the resonance formulas of the carbenoid lb (equation 1) Whereas the carbanionic character is expressed by the resonance formula la, the electrophilic character is represented by Ic. In an analogous way, the reactivity of vinylidene carbenoids 2b is expressed by the mesomeric structures 2a and 2c. 

The question of configurational stability has been investigated first for vinylidene carbenoids and, more recently, for alkylcarbenoids. Vinyl anions are usually considered to be configurationally stable" ° the calculated inversion barrier of the ethenyl anion 10 (R = H) is about 35 kcal mol (equation 4)" . Concerning lithioalkenes, this configurational stability has been confirmed experimentally for a-hydrogen, a-alkyl and a-aryl substituted derivatives . The inversion of vinylidene lithium carbenoids was already... 

The most important method, however, for generating a-halo-substitnted vinylidene carbenoids is the halogen-lithium exchange in dihaloalkenes (equation 24). The reaction is usually performed using n-, s-, or t-butyllithium, whereas metallic lithium is applied only occasionally. Numerous examples , some of which are shown in Table 3, demonstrate the efficiency of the method. 

A similar type of substitution, which clearly shows the electrophilic character, occurs in vinylidene carbenoids. In an early example of this reaction, Kobrich and AnsarP observed that the aUcene 70 results when the fi-configurated vinyl lithium compound 68 is treated with an excess of butyllithium and the fithioafkene 69 formed thereby is protonated (equation 41). Obviously, the nucleophilic attack of the butyl residue on the carbenoid takes place with inversion of the configuration. 

The mechanism outlined in Scheme 12 can explain the nucleophilic substitution at the vinylidene carbenoid At a temperamre that is typical for a particular carbenoid,... 

The nucleophilic attack of f-butyllithium on lithium vinylidene carbenoids has also been used for synthetic purposes in as far as the reaction permits to generate sterically hindered alkenes. Thus, treatment of the dibromoalkene 78 generated from adamantanone with an excess of f-butyllithium results in the formation of the alkene 79 that contains three bulky substituents at the double bond (equation 43) . In an analogous way, a f-butyl residue is introduced into chloroenamine 80 (equation 44) . 

SCHEME 13. Conversion of aldehydes into alkynes under homologation. Application of hydride shifts in vinylidene carbenoids... 

A final carbenoid-type reactivity of a-oxygen-substituted vinylidene carbenoids has been reported for the carbamate 111. When wanned up to temperatures higher than —40 °C, a Fritsch-Buttenberg-Wiechell reanangement takes place to give the alkyne 112 (equation 60). Below that temperature, the lithium compound 111 maintains its nucleophilic reactivity . 

In contrast to their fluoro and chloro counterparts bromo lithium vinylidene-carbenoids have found little interest in organic synthesis. Nevertheless, the reaction... 

The chemistry of lithium carbenoids has been reviewed by Kobrich, who has also reported the preparation of the anti-Bredt olefin (65). The vinylidene carbenoid, which was generated by reaction of (64) with methyl-lithium,... 

Mioskowski and Flack showed that (Z)-2-chloroalk-2-en-l-ols 42 were obtained in excellent yields from a wide variety of aldehydes by addition of ( )-chromium vinylidene carbenoids 41, generated from trichloroalkanes 40 with CrCl2 in THF at room temperature. The same authors also reported CrCh-mediated condensations of x-chloro-gew-trichloroalkanes with aldehydes to give homolallyic alcohols through a hydride rearrangement followed by a Nozaki-Hiyama allylation. ... 

The mechanisms proposed by these groups are quite similar. The most commonly accepted mechanism for the GBB-4C-3CR is depicted in Scheme 7.110. The amine 6g and aldehyde 9z condense to form imine 15i which upon protonation (in the presence of either a Bronstead or Lewis acid) undergoes a nonconcerted [4jt -i- lir] cycloaddition with CIC Izb (which acts as a vinylidene carbenoid) to form 361. Subsequent prototropic shift provides the final aromatic fused product 362. The limitation of this reaction is that absence of nitrogen at the ortfto-position of the pyridine ring does not provide any product. 

The electrophilic reactivity of lithium carbenoids (reaction b) becomes evident from their reaction with alkyl lithium compounds. A, probably metal-supported, nucleophilic substitution occurs, and the leaving group X is replaced by the alkyl group R with inversion of the configuration . This reaction, typical of metal carbenoids, is not restricted to the vinylidene substitution pattern, but occurs in alkyl and cycloalkyl lithium carbenoids as well ". With respect to the a-heteroatom X, the carbenoid character is... 

Another feature of carbenoid-type reactivity is the cyclopropanation (reaction c). Again, this reaction does not only take place in vinylidene but also in alkyl carbenoids . On the other hand, the intramolecular shift of a /3-aryl, cyclopropyl or hydrogen substituent, known as the Fritsch-Buttenberg-Wiechell rearrangement, is a typical reaction of a-lithiated vinyl halides (reaction d) . A particular carbenoid-like reaction occurring in a-halo-a-lithiocyclopropanes is the formation of allenes and simultaneous liberation of the corresponding lithium halide (equation 3). ... 

This stereochemical outcome of the Fritsch-Buttenberg-Wiechell rearrangement is well compatible with the crystal structure of the carbenoid 3 (Figure 1, Scheme 4). The aryl moiety trans to the vinylic chlorine atom is bent towards Cl (C1-C2-C9 116.5°). Thus, migration of the fraw -aryl group with simultaneous liberation of lithium chloride becomes evident. The free vinylidene carbene can be ruled out as the intermediate. 

The synthetic applications of halocarbenoids are mainly determined by the framework bearing the carbenoid center. This article describes the different kinds of synthetic transformations that can be achieved by the use of alkylidene, a-heterosubstituted, cyclopropylidene, vinylidene, and allylidene lithium halocarbenoids. Their particuliar value in organic synthesis results from various rearrangement reactions of the primary adducts formed by reaction of the carbenoid with the electrophile. 

Catalysis by alkali metal ions has recently been reported as an alternative route. In an argon matrix, acetylene forms a n complex with the metal. On irradiation, it isomerizes to the vinylidene form, M C=CH2. When complexed with metals, vinylidene is much more stable, in the same way that metal carbenoids are generally much more stable than carbenes, and rearrangement of a tungsten alkyne complex to a tungsten vinylidene complex has been reported. ... 

The bridging vinylidene complexes Cp2M02 M.-O Ti2-(4e)-C=CR R2 (CO)4 (R, R2 = H, Me) react with donors such as PMc3, P(OMe)3, or CNBu by attack at the carbenoid atom. Similarly, the sulphur from cyclohexenesulphide is transferred to the same atom. 3 3... 

Another mode of activation of o-alkynylanilines 105, involving an alkyne-vinyl-idene isomerization, was reported by Mc-Donald (Scheme 9.40) [191]. High yields of 1-monosubstituted indoles 106 were obtained upon cydoisomerization of terminal o-alkynylanUines 105 using an in situ generated Et3N Mo(CO)5 catalyst. The authors proposed a mechanism involving the initial alkyne-vinylidene isomerization [192-194] of a terminal acetylene 105 into the reactive carbenoid 107. The... 

Cyclobutene derivatives (66) have been synthesized from a diyne and an alkene via a novel Au(I)-catalysed reaction. A highly active vinylidene intermediate (67), formed by a dual Au(I)-mediated activation of the diyne precursor, is believed to act as an alkylidene Au(I)-carbenoid to effect stereospecific cyclopropanation of the alkene the resulting methylenecyclopropane (68) converts to (66) via an Au(I)-catalysed ring-expansion cascade. 

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