Equatorial carboxylic acid derivatives

Phenylthio)nitroalkenes are also excellent intermediates for the synthesis of other heterocyclic ring systems. For example, tetrahydropyran carboxylic acid derivatives are formed by the intramolecular addition of oxygen nucleophile to l-(phenylthio)nitroalkene predominantly as the m-isomer (9.1 1) (see Eq. 4.40). The reaction may proceed via the chair-like transition state with two pseudo-equatorial substituents.50... 

Bile acids can be modified to many derivatives due to their unique molecular structures, as listed in Table 1. First, we can convert the functional groups at the side-chains from carboxylic acid to amide, alcohol, ester, and so on. Second, we can change the length of the side-chains by decreasing or increasing their methylene number. Third, we can regulate the direction of the hydroxyl groups of the skeletons at the axial or equatorial positions. 

Enolates derived from cyclic compounds such as cyclohexane carboxylic acid or cyclohexane carboxalde-hyde generate enolates that are unique. These enolates have an exocyclic double bond that can exist as ( ) and (Z) isomers. The facial and orientational bias in alkylation and condensation reactions of such enolates is influenced by the conformation of the ring it is attached to. Alkylidene cyclohexane enolates show a preference for equatorial attack, just as cyclohexanone derivatives do (sec. 4.7.C,D). 

Evidence for this postulate was provided by epimerization of deuterio-or tritio-labeled derivatives of (148) 117). As the result, a retro-aldol type mechanism in which stereoelectronic requirements are satisfied in the transition state was suggested. The process is depicted in Figure 5. This concept was also applied to the retro-Dieckmann type cleavage of ketone (151) to carboxylic acid (152) (Scheme 31), the facile epimerization of the 3p-axial alcohol (153) to the 3 a-equatorial alcohol (154) under the influence of dilute alkali (followed by esterification) and the cleavage of the 3-ketone (155) to methyl ester (156) on treatment with sodium hydroxide in methanol at 0°C for one hour (Scheme 31). 

Analogously to pyranoses, cyclohexitols and derived carboxylic acids occur in sterically stable chair conformations. The lowest energy has scy//o-inositol with aU substituents in equatorial positions. 

V-Acetylneuraminic acid is a common group in glycoproteins, and it contains both the amide and carboxyl chromophores. As shown in formula 11, this nine-carbon sugar derivative has an equatorial amido group on C-5 and both a hydroxyl group and a carboxyl group on the anomeric carbon atom. 

The carboxyl chromophore is axial for the a anomer and equatorial for the p anomer. The sugar was studied as the carboxylate anion as it has a (low) piC of 2.6, and the compound is degraded in acidic solution. The c.d. spectrum of this compound contains contributions from the carboxylate n-jr at 217 nm, the amide n-tr at 210 nm, and the amide 7T7r at 190 nm. Apparently, all of these bands are positive, giving rise to a c.d. spectrum (see Fig. 29) having " a maximum at 199 nm and a shoulder at 210 nm. The c.d. spectra of a number of derivatives confirmed these assignments. 

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