Carbanion equivalent formations

Transition Metal-Mediated Carbanion Equivalent Formations... 

The decarboxylation reaction usually proceeds from the dissociated form of a carboxyl group. As a result, the primary reaction intermediate is more or less a carbanion-like species. In one case, the carbanion is stabilized by the adjacent carbonyl group to form an enolate intermediate as seen in the case of decarboxylation of malonic acid and tropic acid derivatives. In the other case, the anion is stabilized by the aid of the thiazolium ring of TPP. This is the case of transketolases. The formation of carbanion equivalents is essentially important in the synthetic chemistry no matter what methods one takes, i.e., enzymatic or ordinary chemical. They undergo C—C bond-forming reactions with carbonyl compounds as well as a number of reactions with electrophiles, such as protonation, Michael-type addition, substitution with pyrophosphate and halides and so on. In this context,... 

Reaction of saturated acylzirconocene chlorides with (CH3)2Cu(CN)Li2 gives the secondary alcohol (73%), and D20 work-up of the reaction mixture gives the a-deuterio alcohol. This observation suggests the formation of a ketone—zirconocene complex (Scheme 5.40 see also Section 5.3.2.1). Thus, for the reaction of a,p-unsaturated acylzirconocene chlorides with R2Cu(CN)Li2, initial formation of an unsaturated ketone—zirconocene complex followed by 1,3-rearrangement of the zirconocene moiety to an oxazirconacyclopentene, which is a ketone carbanion equivalent, has been proposed (Scheme 5.41). 

To gain access to a broader spectrum of natural products including protease inhibitors, C-C-bond formation is often required in central steps. For this purpose polymer-supported carbanion equivalents have been investigated (Chapter 4). Several strategies leading to supported acyl anion equivalents are presented these have been employed for general synthesis of protease inhibitors containing the a-hydroxy-jS-amino motif. 

Alcohols can also be obtained from epoxides, aldehydes, ketones, esters, and acid chloride as a consequence of C-C bond formation. These reactions involve the addition of carbanion equivalents through the use of Grignard or organolithium reagents. 

Earlier we mentioned the Wurtz reaction as being one of the simplest approaches to the formation of C-C bonds. In this reaction, the alkyl halide serves as the electrophile (carbocation equivalent) and the organometallic derivative plays the role of the nucleophile (carbanion equivalent). We have also seen that this old reaction has recently become a feasible route for the creation of C-C bonds due... 

X = OTf) may fail to accomplish metal exchange and consequently hinder the formation of the alke-nylchromium reagent. Few examples of the use of enol triflates as progenitors of vinyl carbanion equivalents have appeared. Consequently, the work from Takai and coworkers is particularly useful. The alkenylchromiums generated from enol triflates are functionally indistinguishable from those generated from iodoalkenes (equation 65 and table 10). This fact is disclosed by comparison of Table 9 with Table 10. 

Finally, ketone formation by acylation of carbanions can proceed in several ways, including masking of the ketonic product until isolation, the use of carbanion equivalent reagents which do not readily react with the product or the use of substrates which are more reactive than the ketone towards acylation. An... 

The most systematically investigated acyl anion equivalents have been the IMS ethers of aromatic and heteroaromatic aldehyde cyanohydrins, TBDMS-protected cyanohydrins, benzoyl-protected cyanohydrins, alkoxycarbonyl-protected cyanohydrins, THP-protected cyanohydrins, ethoxyethyl-protected cyanohydrins, a-(dialkylamino)nitriles, cyanophosphates, diethyl l-(trimethylsiloxy)-phenylmethyl phosphonate and dithioacetals. Deprotonation of these masked acyl anions under the action of strong base, usually LDA, followed by treatment with a wide variety of electrophiles is of great synthetic value. If the electrophile is another aldehyde, a-hydroxy ketones or benzoins are formed. More recently, the acyl carbanion equivalents formed by electroreduction of oxazolium salts were found to be useful for the formation of ketones, aldehydes or a-hydroxy ketones (Scheme 4). a-Methoxyvinyl-lithium also can act as an acyl anion equivalent and can be used for the formation of a-hydroxy ketones, a-diketones, ketones, y-diketones and silyl ketones. - ... 

Several PLP-dependent enzymes catalyze elimination and replacement reactions at the y-carbon of substrates, an unusual process which provides novel routes for mechanism-based inactivation. An example of this class of enzymes is cystathionine y-synthase [0-succinylhomoserine (thiol)-lyase], which converts (7-succinyl-L-homoserine and L-cysteine to cystathionine and succinate as part of the bacterial methionine biosynthetic pathway (Walsh, 1979, p. 823). Formation of a PLP-stabilized o-carbanion intermediate activates the )8-hydrogen for abstraction, yielding j8-carbanion equivalents and allowing elimination of the y-substituent. The resulting j8,y-unsaturated intermediate serves as an electrophilic acceptor for the replacement nucleophile. Suitable manipulation of the j8-carbanion intermediate allows strategies for the design of inactivators which do not affect enzymes which abstract only the a-hydrogen. 

From such experiments, it was proposed that the 2-amino-3-hydroxycyclopent-2-enone moiety 232 may be synthesized from succinate and glycine to give 5-aminolevulinic acid, which undergoes an intramolecular cyclization facilitated by the formation of an a-carbanion equivalent, possibly through the intermediacy of a Schiff base with a pyridoxal phosphate cofactor. As shown in Figure 3.70,... 

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