Diols hydroxy esters

The DKR of functionalized alcohols such as diols, hydroxy esters, hydroxy aldehydes, azido alcohols and hydroxy nitriles was also taken up as the synthetic uhlity of the products is very high besides such a study will bring out the effect of multifunctional substrates under these reaction conditions to broaden the scope of DKR. Initially, the DKR of diols was achieved with diruthenium catalyst 1... 

Butylethylidene and 1-phenylethylidene ketals were prepared selectively from the C4-C6, 1,3-diol in glucose by an acid-catalyzed transketalization reaction [e.g., Me3CC(OMe)2CH3, TsOH/DMF, 24 h, 79% yield PhC(OMe)2Me, TsOH, DMF, 24 h, 90% yield, respectively]. They are cleaved by acidic hydrolysis AcOH, 20°, 90 min, 100% yield, and AcOH, 20°, 3 days, 100% yield, respectively. Ozonolysis of the /-butylmethylidene ketal affords hydroxy ester, albeit with poor regiocontrol, but a more sterically differentiated derivative may give better selectivity, as was observed with the ethylidene ketal. ... 

Polyesters have been obtained in organic medium by polyesterification of hydroxy acids,328,329 hydroxy esters,330 stoichiometric mixtures of diols and diacids,331-333 diols and diesters,334-339 and diols and cyclic anhydrides.340 Lipases have also been reported to catalyze ester-ester interchanges in solution or in die bulk at moderate temperature.341 Since lipases obviously catalyze the reverse reaction (i.e., hydrolysis or alcoholysis of polyester), lipase-catalyzed polyesterifications can be regarded as equilibrium polycondensations taking place in mild conditions (Scheme 2.35). 

Davis has described an approach to related 1,3-diol synthons [49] (Eq. 20). Silylation of the -hydroxy ester 129 with diisopropylchlorosilane, followed by fluoride ion-catalyzed intramolecular hydrosilylation generated a 1 1 diastere-omeric mixture of acetals 131. These acetals were shown to undergo diastereo-selective nucleophilic additions vide infra). 

Example The substituted 1,4-diol (4) must surely be made by a method which uses the symmetry of the structure. Disconnection (a) would require Grignard reagent (5) whose OH group would have to be protected. Disconnection (b) gives hydroxy ester (6) and here no protection is necessary as the internal ester (lactone) (7) serves the purpose. 

A mixture of benzaldehyde (1.06 g, 10 mmol), ethane-1,2-diol (0.62 g, 10 mmol) and commercial grade cadmium iodide (1.85 g, 5 mmol) were thoroughly mixed at room temperature in an Erlenmeyer flask and placed in a commercial micro-wave oven operating at 2450 MHz frequency. After irradiation of the mixture for 1.5 min (monitored vide TLC) it was cooled to room temperature, extracted with dichloromethane, washed with sodium thiosulfate and dried over anhydrous Na2S04- Evaporation of the solvent gave almost pure products and there was no evidence for the formation of any hydroxy ester or iodoester. Further purification was achieved by column chromatography on silica gel using 1 5 chloroform-petroleum ether as eluent. 

There are many other acyl anion equivalents that are dealt with in detail in Strategy and Control.5 An example of this general approach is phenaglycodol 19 used in the treatment of mild epilepsy. This 1,2-diol could be made in many ways but disconnection of two methyl groups reveals an a-hydroxy-ester 20 that could be made by addition of cyanide to the ketone 21. 

Aldol condensation of the zinc enolate of resin-bound alkyl ester 29 with aromatic aldehyde or ketone forms a P-hydroxy ester, which upon treatment with DIBAL-H leads to simultaneous reduction and cleavage of the ester moiety from the resin to give a soluble 1,3-diol 31 [31], Parallel synthesis utilizing three ester and nine carbonyl building blocks afforded a library of 27 analogs which was screened for antioxidative efficiency using a ferric thiocyanate assay. 

As shown in Scheme 7, lipase-assisted resolution of the racemic hydroxy ester ( )-45 allowed for isolation of chiral non-racemic enantiomer 45, which served to arrive at both diol 46 (via ester reduction) and all-cis epoxide 47 (via ferf-butylhydroperoxide treatment). In a remarkably flexible fashion, cyclopentene 46 was then used as the direct precursor of 3-methyl-branched P-D-ribocarbafuranose 48, P-D-... 

The possibility to obtain amino diols from (3-amino-ot-hydroxy esters (see above) was crucial in the exploration of an AA approach towards D-ango-... 

Monoesterification of HO(CH OHAlkenes react with diols under oxidative carbonylation conditions catalyzed by PdCl, and CuCl, to give hydroxy esters (equation I). Internal alkenes show similar reactivity. 

Raney nickel hydrogenation, produced an epimeric mixture of hydroxy-esters (446 R = C02Et) and diols (446 R = CH2OH). Treatment of the corresponding hydroxy-acids (446 R = CO2H) with methyl-lithium, followed by Jones oxidation, yielded the two epimeric diketones (447) in the ratio 9 1. Aldoliza-tion of (447 / -Me) with potassium t-butoxide gave epipatchoulenone (448 R = H, R = Me) while similar treatment of (447 a-Me) afforded patch-oulenone (448 R = Me, R = H). 

Ester reduction. A method for the conversion of dicarboxylic acids to CD-hydroxycarboxylic acids involves formation and reduction (with NaBH ) of dilactones in which the two carbonyl residues are linked by tm OCH2O chain. Arylpyruvic esters can be reduced to either the a-hydroxy esters or 1,2-diols. ... 

Reaction of bromide with the diol derived from a cinnamate provides access to [3-aryl a-hydroxy esters (Scheme 3.29) [340], The regiochemical control is not complete. 

In this chapter, we attempt to review the current state of the art in the applications of cinchona alkaloids and their derivatives as chiral organocatalysts in these research fields. In the first section, the results obtained using the cinchona-catalyzed desymmetrization of different types of weso-compounds, such as weso-cyclic anhydrides, meso-diols, meso-endoperoxides, weso-phospholene derivatives, and prochiral ketones, as depicted in Scheme 11.1, are reviewed. Then, the cinchona-catalyzed (dynamic) kinetic resolution of racemic anhydrides, azlactones and sulfinyl chlorides affording enantioenriched a-hydroxy esters, and N-protected a-amino esters and sulftnates, respectively, is discussed (Schemes 11.2 and 11.3). 

Both a-hydroxy esters and 1.2-diols are widely used chiral synthetic intermediates. Development of a broadly effective and practicable catalyst for highly enantioselective hydrogenation of a-keto esters to a-hydroxy esters has not yet been reported [29,30]. We have observed similarly unsatisfactory results to date in the hydrogenation of a-keto esters with our cationic DuPHOS-Rh and BPE-Rh catalysts. An alternative approach to optically active a-hydroxy esters could... 

We have found that the Et-DuPHOS-Rh catalysts are capable of effecting smooth and highly enantioselective hydrogenation of E/7. mixtures of enol esters 26 (R = Me, Ph, etc.) [31]. As delineated in Table 3, a wide substrate scope has been demonstrated with enantioselectivities of > 95% ee. Products 27 thus obtained may be directly converted to a-hydroxy esters 28 through mild acidic hydrolysis in alcohol, or alternatively 27 may be reduced to the corresponding 1,2-diols 29 by the use of reagents such as LiAlH4, with no loss of enantiomeric purity. 

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