Energy hydroxy esters

This facilitates intramolecular hydride transfer resulting in a Ru-hydroxy ester complex (66) which readily releases the chiral product. When an (R)-BINAP-Ru catalyst is used, the R enantiomer is obtained in >99% ee. The chirality of the BINAP ligand accounts for the difference in energy between the possible transition states TS and TS. ... 

Computational efforts to describe the conformational preferences of (R,R)-tartaric acid and its derivatives - mainly for isolated molecules - were made recently [18-25]. The conformations of these molecules also attracted attention from experimental chemists [22-40]. (/ ,/ [-tartaric acid and its dimethyl diester were observed in crystals, in conformations with extended carbon chain and planar a-hydroxy-carboxylic moieties (T.v.v and Tas for the acid and the ester, respectively) [25-28] (see Figure 2). The predominance ofthe T-structure was also shown by studies of optical rotation [31], vibrational circular dichroism (VCD) [23], Raman optical activity [32, 35], and nuclear magnetic resonance (NMR) [22, 33, 34]. The results of ab-initio and semiempirical calculations indicated that for the isolated molecules the Tsv and T as conformers were those of lowest energy [22, 21, 23, 25]. It should be noted, however, that early interpretations of NMR and VCD studies indicated that for the dimethyl diester of (/ ,/ [-tartaric acid the G+ conformation is favored [36-38]. 

Hydroxy derivatives. 2-Hydroxy derivatives usually exist as the oxo tautomers, unless the hydroxy tautomer is appreciably stabilized by electron-withdrawing or chelating substituents. The tendency for enolic hydroxy compounds to revert to the oxo form can be understood by reference to simple aliphatic ketones where the keto-enol equilibrium constants are of the order of 108. In the five-membered heterocycles under consideration, this tendency will be in opposition to the loss of aromatic resonance energy that increases in the order furan << thiophene < pyrrole. For the 2-hydroxy compounds 217 some extra stabilization of the oxo tautomers 218 and 219 is derived from the resonance energy of the X-C=0 group, which by analogy with open-chain compounds should increase in the sequence thiolester, ester << amide. 

Figure 4. A linear free-energy relationship between the logarithm of rate constant for metal-catalyzed hydrolysis log fcMeOK) of p-nitrophenyl acetate (NPA), dinitrophenyl acetate (DNPA), and trinitrophenyl acetate (TNPA) and the hydrolysis constant (MeH2O MeOH + H+) for the formation of the corresponding hydroxy complex. This relationship provides support for the argument that the MeOH species is involved in a direct nucleophilic attack on the carbonyl carbon of the nitrophenyl acetate esters.

More recently Openshaw and Whittaker3 in a synthesis of emetine alkaloids needed to effect condensation of an amine with a low-energy ester and in the particular case studied found that use of hydroxy pyridine raised the yield from 2% to 87%. Twelve other mono- or polyhydroxylated heterocyclics were examined, but 2-hydroxypyridine was clearly superior. 

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