Allene carbanions

A synthesis of 3(277)-furanones (180) has been described in which allenic carbanions are generated as precursors of the allenes (179) which function as j3-ketoaldehydes (Scheme 40) (75TL1741). 

To understand the carbanion mechanism in flavocytochrome 62 it is useful to first consider work carried out on related flavoenzymes. An investigation into o-amino acid oxidase by Walsh et al. 107), revealed that pyruvate was produced as a by-product of the oxidation of )8-chloroalanine to chloropyruvate. This observation was interpreted as evidence for a mechanism in which the initial step was C -H abstraction to form a carbanion intermediate. This intermediate would then be oxidized to form chloropyruvate or would undergo halogen elimination to form an enamine with subsequent ketonization to yield pyruvate. The analogous reaction of lactate oxidase with jS-chlorolactate gave similar results 108) and it was proposed that these flavoenzymes worked by a common mechanism. Further evidence consistent with these proposals was obtained by inactivation studies of flavin oxidases with acetylenic substrates, wherein the carbanion intermediate can lead to an allenic carbanion, which can then form a stable covalent adduct with the flavin group 109). Finally, it was noted that preformed nitroalkane carbanions, such as ethane nitronate, acted as substrates of D-amino acid oxidase 110). Thus three lines of experimental evidence were consistent with a carbanion mechanism in flavoenzymes such as D-amino acid oxidase. 

Studies with the suicide inhibitor 2-hydroxy-3-butynoate (103, 113) have provided further support for a carbanion mechanism operating in flavocytochrome. The 2-hydroxy-3-butynoate results in a carbanion intermediate that can resonate to an allenic carbanion, which can then form a covalent adduct with the flavin cofactor (Fig. 11). This adduct is highly reactive and cyclizes to form an inactive modifled flavin group (113, 114). 

Few furan 3-carbanions are stable except at low temperatures and only recently have they been extensively used. Ring opening is common. Gilchrist and Pearson218 report that the fate of the unusually stable carbanion 84 depends upon both solvent and temperature. At room temperature and in benzene it partly opens giving the allenic ketone 85 in ether it is fairly stable. In hexane, the 3-lithiofuran is precipitated unless heated to 65 C when it isomerizes to acetylenic salts giving the allenic ketone 85 with water. 

In the second example, one carbon atom of the future allene group is contributed by the sulfoxide 72, which is first converted to the ketone 74 by LDA treatment followed by quenching of the resulting carbanion with methyl 3-phenylpropanoate (73). To convert the now complete carbon framework into a central allene unit, the enol triflate of 74, intermediate 75, is produced under the conditions given in the scheme. Ultimate butyllithium treatment of 75 then furnishes the alkylated allene 76 [23],... 

It was recognized in early examples of nucleophilic addition to acceptor-substituted allenes that formation of the non-conjugated product 158 is a kinetically controlled reaction. On the other hand, the conjugated product 159 is the result of a thermodynamically controlled reaction [205, 215]. Apparently, after the attack of the nucleophile on the central carbon atom of the allene 155, the intermediate 156 is formed first. This has to execute a torsion of 90° to merge into the allylic carbanion 157. Whereas 156 can only yield the product 158 by proton transfer, the protonation of 157 leads to both 158 and 159. 

The intermediate product 162, formed from the nudeophilic addition of 1,2-alle-nic phosphonate or 1,2-allenic phosphine oxide with allylic alcohol, would also undergo a Claisen rearrangement to form 2-oxo-5-alkenyl phosphonate or phosphine oxide 163 [85], The rearrangement is accelerated by the carbanionic nature of the intermediate 162. For the conjugate addition step, the reaction temperature is crucial since the reaction at 0 °C afforded mainly /i,y-unsaturated product whereas a,/8-unsaturated products were formed at 20 °C. 

If allenes bear a potential leaving group in the a-position to the cumulene system, they are very attractive substrates for palladium-catalyzed substitutions. Examples are a-allenic acetates and particularly a-allenic phosphates, which react under palladium(O) catalysis with carbanions derived from /3-diesters, /i-keto esters, a-phenylsulfonyl esters and glycine ester derivatives. They lead to /3-functionalized allenes such as 86, 89 and 93 (Eqs. 14.9-14.11) [45 18]. 

Fluoride ion promoted cleavage of propynylsilanes and subsequent reaction of the carbanion with carbonyl compounds produces allenic compounds. The reaction with formaldehyde and pivaldehyde fails, but both the allenic and acetylenic products are obtained from the reaction with acrolein and benzaldehyde [49]. Allylsilanes react with carbonyl compounds to produce but-3-en-l-ols [50],... 

R. Epsztein, "The Formation and Transformations of Allenic-o-Acetylenic Carbanions", in E. Buncel, T. Durst (ed.), "Comprehensive Carbanion Chemistry", pan B, Elsevier, 1984, p. 107. 

Synthesis of allenes by alkenylation of magnesium aikyiidene carbenoids with a-suifonyi iithium carbanions... 

The electrophilic reaction of magnesium alkylidene carbenoids with other nucleophiles than the original Grignard reagent can also be carried out. For example, treatment of magnesium alkylidene carbenoid 157, derived from 147, with a-sulfonyl lithium carbanion afforded allenes 159 in moderated yields (equation 39/. ... 

The proposed mechanism is as follows First, the a-sulfonyl lithium carbanion attacks the electrophilic carbenoid carbon atom to give the vinyhnagnesium intermediate (158). As the sulfonyl moiety is a good leaving group, a /-elimination takes place to afford the allenes (159). 

In principle, the nucleophile can attack the allene at two different positions, but the products show exclusive attack at the central carbon atom, similarly to other nucleophilic additions to allenes (Eglinton et al., 1954 Stirling, 1964b Taylor, 1967). This may result from the stabilization of the carbanion (194), formed by attack at this position, by the two phenyl groups. The ion (194) may be protonated at either one of the terminal positions of the allenic system, and low amounts of... 

The studies by Tolbert on indenyl carbanions were extended to the 2 halogenated anions. In this interesting cases halide ejection was shown to override the electron transfer chemistry and an hypovalent intermediate of the carbene or allene type is formed leading to C-H insertion products [137, 138, 139],... 

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