Carbanion equivalents

The main Uab synthetic pathway is illustrated in Scheme 6.1 and corresponds to C-acylation of an o-aminobenzyl carbanion equivalent. Acylation is normally followed by in situ cyclization and aromatization. This route is therefore closely related to the cyclizations of o-aminobenzyl ketones described in Section 2.3 but the procedures described here do not involve isolation of the intermediates. 

Reactions with Acyl Garbanion Equivalents. Alkyl substituted carbanions CRXY with potential leaving groups X, Y, and acyl carbanion equivalents or CHRX (342) react with alkylboranes, providing products with mixed alkyl groups derived from both reagents. 

However, if we can design some sophisticated routes to generate carbanion equivalents in the active site of the enzyme, carboxylation reaction might be possible. In fact, acetyl-CoA is carboxylated with the aid of biotin in the biosynthetic pathway of long-chain fatty acids. 

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,... 

As can be seen from the above examples, the decarboxylation reaction can be said to generate carbanion-equivalent, which is capable of undergoing the enantioselective reactions not only with a proton but also with a carbon electrophile in an aqueous medium. In the future extension of this field, this characteristic point should be utilized for the design of the unique reactions. 

In terms of the carbanion equivalent, the enolase superfamily has a strong relation with decarboxylation reaction. This family is characteristic in its promiscuity. If one is reminded of the phrase lock and key theory for the relation between the substrate and the enzyme, the word promiscuity of the enzyme may be unbelievable. However, in addition to natural promiscuity, we can change the enzyme to be promiscuous by introducing mutation, especially in the case of the enolase superfamily. This will be one of the challenging problems in future. For that purpose, biotechnology and informatics skill will be essential tool in addition to precise analysis of the reaction mechanism. 

In contrast to the transition metals, where there is often a change in oxidation level at the metal during the reaction, there is usually no change in oxidation level for boron, silicon, and tin compounds. The synthetically important reactions of these three groups of compounds involve transfer of a carbon substituent with one (radical equivalent) or two (carbanion equivalent) electrons to a reactive carbon center. Here we focus on the nonradical reactions and deal with radical reactions in Chapter 10. We have already introduced one important aspect of boron and tin chemistry in the transmetallation reactions involved in Pd-catalyzed cross-coupling reactions, discussed... 

In a similar manner, starting from 2-methylchloride-naphtho[l,8-de][l,2,3]triazine and magnesium, via a novel sonication-promoted Barbier reaction, an a-aminomethyl carbanion equivalent is generated which reacts in situ with a variety of carbonyl compounds. Subsequent catalytic hydrogenolysis of the triazine moiety yields the corresponding amines <00TL4685>. Sterically controlled regiospecific cyclization of aldose-5-ethyl-l,2,4-... 

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 [Pg.175]

The use of organozirconium compounds as carbanion equivalents is greatly facilitated by trans metallations to the more reactive aluminum [11,100], copper [104—106], nickel [96—98], and palladium [99] derivatives. Copper-catalyzed carbon—carbon bond-forming reactions of alkyl- and alkenylzirconocene compounds have been particularly well studied, and have found considerable application in organic synthesis [107,108]. 

This method for preparing 2-phenyl-1-pyrroline, and assorted 2-substituted 1-pyrrolines, is one of the best currently available, particularly because it reproducibly affords clean materials. Generally, the procedure is amenable to various aromatic esters 2 it has also been applied successfully to aliphatic esters (Table I).3 An advantage of this method is the use of readily available, inexpensive N-vinyl-pyrrolidin-2-one as a key starting material. This compound serves effectively as a 3-aminopropyl carbanion equivalent. The method illustrated in this procedure has been extended to include the synthesis of 2,3-disubstituted pyrrolines. Thus, alkylation of the enolate of the intermediate keto lactam, followed by hydrolysis, leads to various disubstituted pyrrolines in good yields (see Table II).3... 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Kirk L. Sorgi, Cynthia A. Maryanoff, David F. McComsey, and Bruce E. Maryanoff 215 N-VINYLPYRROLIDIN-2-ONE AS A 3-AMINOPROPYL CARBANION EQUIVALENT IN THE SYNTHESIS OF SUBSTITUTED 1-PYRROLINES PREPARATION OF 2-PHENYL-1-... 

Biocatalytk decarboxylation is a imique reaction, in the sense that it can be considered to be a protonation reaction to a carbanion equivalent intermediate in aqueous medimn. Thus, if optically active compoimds can be prepared via this type of reaction, it would be a very characteristic biotransformation, as compared to ordinary organic reactions. An enzyme isolated from a specific strain of Alcaligenes bronchisepticus catalyzes the asymmetric decarboxylation of a-aryl-a-methyhnalonic acid to give optically active a-arylpropionic acids. The effect of additives revealed that this enzyme requires no biotin, no co-enzyme A, and no ATP, as ordinary decarboxylases and transcarboxylases do. Studies on inhibitors of this enzyme and spectroscopic analysis made it clear that the Cys residue plays an essential role in the present reaction. The imique reaction mechanism based on these results and kinetic data in its support are presented. 

The carbanion equivalent from a Grignard reagent is also a strong base. pATa values for alkanes are typically about 50, and for aromatics about 44. Not surprisingly, a Grignard reagent reacts readily with... 

Then, in what is formally a reverse of this reaction, this carbanion equivalent can attack another aldose, such as erythrose 4-phosphate, extending its chain... 

C synthons, synthetic equivalents of which being the amino-acetaldehyde-derived metallated aminonitrile D bearing the chiral auxiliary (S,S)-53 and an a,P-unsaturated ester E, respectively. This should make it possible to open up a pathway to an enantioselective conjugate addition of an a-aminoacyl carbanion equivalent D to enoates in order to access the target 3-substituted 5-ainino-4-oxo esters. 

Organometallic compounds which contain a carbon-metal bond are the most reactive carbon nucleophiles. In most cases they are also powerful bases and must be prepared and used under strictly anhydrous and aprotic conditions. A very common way to produce organometallic compounds is to reduce alkyl halides with active metals. Grignard reagents and organolithium compounds are routinely produced in this manner. The transformation is a two-electron reduction of the alkyl halide to a carbanion equivalent the metal is oxidized. 

The bromine substituent can be metallated to give a carbanion equivalent /3 to the acetal group. Now since the acetal is easily hydrolyzed to the ketone, it is... 

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