Carboxylate enolate

The first part is a Birch reduction, with NH3 as the proton source. It gives the carboxylate enolate as the initial product. When the alkyl halide is added, the enolate acts as a nucleophile to give the C3-C7 bond in an Sn2 reaction. 

Ivanov Reagents are carboxylate enolates (enediolates, or carboxyl 0 acid dianions) derived from phenyl acetic acid or... 

Under basic conditions, penams can undergo S(l)-C(2) bond cleavage via generation of the carboxylic enolate which subsequently releases an intermediate thiolate 9 (Scheme 5). The latter can then react with an electrophile in either an inter- <1995T10715, 1995T10723> or intramolecular way <1996TL4431>. 

Fig. 13.10. Formation of carboxylate enolates ("carboxylic acid dianions") by reaction of carboxylic acid salts with strong bases.

The simple diastereoselectivity of aldol reactions was first studied in detail for the Ivanov reaction (Figure 13.45). The Ivanov reaction consists of the addition of a carboxylate enolate to an aldehyde. In the example of Figure 13.45, the diastereomer of the /1-hydroxycarboxylic acid product that is referred to as the and-diastereomer is formed in a threefold excess in comparison to the. vy/j-diastereoisomer. Zimmerman and Traxler suggested a transition state model to explain this selectivity, and their transition state model now is referred to as the Zimmer-man-Traxler model (Figure 13.46). This model has been applied ever since with good success to explain the simple diastereoselectivities of a great variety of aldol reactions. 

Fig. 10.40. The Ivanov reaction. For the generation of the carboxylate enolate, see Figure 10.8.

In the case of mercurated tiglic acid adducts (12), the erythro product is obtained with aqueous Na2S, and an ionic mechanism has been proposed with an intermediate carboxylate enolate (25). Sodium tri-thiocarbonate and, especially, 1,3-propanedithiol exhibit a preference for retention of configuration leading to the erythro isomer. Such sulfur-containing reagents are probably capable of intramolecular hydrogen atom delivery as illustrated schematically in (26), and they also promote demercuration by an ionic mechanism. 

Stereoselective addition of a dithiane anion to chiral 2-methyl-3-trimethylsilyl-3-buterud combined with the stereoselective addition of a Grignard reagent to the chi a-alkoxy ketone affords a practical method for the construction of a,y-dimethyl-a,3-dihydroxy compounds, useful intermediates for the synthesis of erythronolides (Scheme 33). -Hydroxy cartmxylic esters were synthesized by the addition of ethyl l,3-dithiolanyl-2-carboxylate enolate to a chiral aldehyde, followed by desulfurization. ... 

Although there are only a few examples of alkylations of carboxylate enolates which are exocyclic to five-membered carbocyclic rings, the usual steric factors seem to control the stereoselectivity of these reactions. Thus, the dienolate (111) underwent reaction with 4-bromo-l-butene anti to the methoxymethyl substituents with high diastereoselectivity " and enolates derived from norbomane-2-carboxylates (112)... 

There are many examples of intramolecular cyclizations of carboxylate enolates which lead to fused-and bridged-ring systems. The reaction shown in Scheme 71, which was used by Danishefsky et al. as a part of their synthesis of ( )-quadrone, is illustrative. ... 

Enol Ethers, Enol Carboxylates, Enol Phosphates and Enol Sulfonates... 

When a benzoic acid derivative is reduced, the final protonation step does not occur, and a carboxylate enolate is obtained. The enolate can be protonated upon workup to give the usual product, or it can be alkylated by addition of an electrophile. The proton or the electrophile adds ipso to the carboxylate group exclusively. This position has the largest coefficient in the HOMO of the pentadienyl anion. 

Figure 8.4 Proposed cinchonine/methyl 2- oxocyclopentane-carboxylate enol tautomer complex approaching the Re-face of methyl benzylidenecarbamate.

The glycosaminoglycan epimerases are part of a superfamily of lyases and epimerisases whose active sites stabilise carboxyl enolates, similar to the mannuronate epimerases in alginate biosynthesis. ... 

The Ivanov reaction is the preparation of a 3-hydroxy acid by reaction of the magnesium dianion of a carboxylic acid with an aldehyde or ketone." In a seminal paper, Zimmerman and Traxler investigated the Ivanov reaction of phenylacetic acid and benzaldehyde and obtained anti and syn 3-hydroxy acids (127) and (128) in 69% and 22% yields, respectively (equation 85). The observed stereochemistry was rationalized with a cyclic, chair-like transition state in which a magnesium cation is chelated by one oxygen each of the carboxylate enolate and the aldehyde (the Zimmerman-Traxler transition state ). 

Several 1,3-diene syntheses involving elimination reactions that are catalyzed by Pd(Ph3P)4 have been reported. The first involves the Et3N mediated elimination of HOAc from allylic acetates in refluxing THF. A complementary procedure involves the Pd(Ph3P)4 catalyzed decarboxylative elimination of /3-acetoxy-carboxylic acids (eq 46). The substrates are easily prepared by the condensation of enals and carboxylate enolates irrespective of the diastereomeric mixture, ( )-alkenes are formed in a highly stereocontrolled manner. The geometry of the double bond present in the enal precursor remains unaffected in the elimination and the reaction is applicable to the formation of 1,3-cyclohexadienes. 

The reactions of aldehydes with carboxylate enolates are stereochemical-ly related to the Ivanov reaction (dianions of arylacetic acids -t carbonyl compounds), named after the Bulgarian chemist Dimitar Ivanov Popov (1894-1975). 

Regio- and stereocontrolled synthesis of 1,3-dienes was accomplished by decar-boxylative elimination from 3-acetoxy-4-aIkenoic acids, which are obtained from enals and carboxylate enolates (Scheme 13, Table The reaction was applied to the synthesis of bombykol. The reaction was also used for the construction of a polyene system in vitamin... 

Although malonate derivatives were described previously, one example is included here to demonstrate their use as a carboxyl enolate. Reaction of 4.87 with carbonyl diimidazole (CDI, see chapter two, section 2.4) gave the acyl imidazole (a very highly activated acyl derivative), which reacted with the magnesium enolate of... 

Semiempirical calculations have modelled the addition of dimetal enolate salts of carboxylic enolates to aldehydes, and have been extended to predict the kinetic stereoselectivities of such reactions. ... 

A new stereocontrolled diene synthesis via a palladium-catalysed decarboxy-lative elimination of the adducts from a,jS-unsaturated aldehydes and carboxylate enolate has been reported and applied to the synthesis of insect pheromones and to regiospecifically substituted cyclohexadienes (Scheme 32). ... 

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