1,3-Diol monoesters

The mechanism of the aldol-Tishchenko reaction has been probed by determination of kinetics and isotope effects for formation of diol-monoester on reaction between the lithium enolate of p-(phenylsulfonyl)isobutyrophenone (LiSIBP) and two molecules of benzaldehyde. ". The results are consistent with the formation of an initial lithium aldolate (25) followed by reaction with a second aldehyde to form an acetal (26), and finally a rate-limiting intramolecular hydride transfer (Tishchenko... 

In 1998, Hasanayn and Streitwieser reported the kinetics and isotope effects of the Aldol-Tishchenko reaction . They studied the reaction between lithium enolates of isobu-tyrophenone and two molecule of beuzaldehyde, which results iu the formation of a 1,3-diol monoester after protonation (Figure 28). They analyzed several aspects of this mechanism experimentally. Ab initio molecular orbital calculatious ou models are used to study the equilibrium and transition state structures. The spectroscopic properties of the lithium enolate of p-(phenylsulfonyl) isobutyrophenone (LiSIBP) have allowed kinetic study of the reaction. The computed equilibrium and transition state structures for the compounds in the sequence of reactions in Figure 28 are given along with the computed reaction barriers and energy in Figure 29 and Table 6. 

FIGURE 28. Reaction sequence for formation of a diol monoester from the reaction between a hthium enolate and two aldehyde molecules. Reprinted with permission from Reference 29. Copyright 1998 American Chemical Society... 

It ib often customary to hydrolyze 1,2-diol monoesters t tinted from olefins directly to 1,2-diols, without determining the site of attack in the presumed epoxide intermediate. This iB regrettable in those instances where information on the direction of ring lniAMj. might be useful. Where the structure of the 1,2-diol monoesters cannot be specified, only the formula of the 1,2-diol ultimately isolated is shown here (ejg. Eq. 747). 

In conclusion of the present section, attention may he directed to two other strong mineral acids that have been condensed with ethylene oxides nitric acid and perchloric acid. These reagents, provided they are ueed as cold dilute aqueous solutions to avoid oxidative reactions, give 1,2-diol monoesters. 

Several instances ore known in which a unsaturated acids yield ./ -dihydroxy acids on treatment with peracetic aoid and alkaline hydrolysis of the resultant 1,2-diol monoesters. 37- Although... 

Fuji and co-workers have demonstrated the use of a PPY derivative that utilizes remote stereochemistry and an interesting induced fit process to control selectivity [21]. Upon acylation of catalyst 20, a conformational change occurs, stabilizing the intermediate N-acyliminium ion 21 (Fig. 2a,b). Chemical shifts in the XH NMR and nOes observed support a Jt-Jt interaction between the electron-rich naphthyl ring and the electron-deficient pyridinium ring. This blocks the top face of the catalyst and directs attack of the alcohol from the bottom face. Catalyst 20 effects resolutions of diol-monoesters and amino alcohol derivatives such as 22 and 23 with moderate to good selectivity factors (fcrei=4.7-21, see Fig. 2c) [22]. 

A syn-2-amino alcohol, complexed with Yb(III), catalyses the aldol-Tishchenko reaction of aliphatic ketones with aromatic aldehydes to give anti- 1,3-diol monoesters with three adjacent stereocentres in high yield, de, and ee.141 ... 

Amongst this class of reactions, the Sml2-catalysed intramolecular Tishchenko reaction developed by Evans and Hoveyda has found widespread application.39 In this transformation, excess aldehyde is used with a sub-stoichiometric amount of Sml2 to convert (3-hydroxy ketones into anti-diol monoesters in high yield and high diastereomeric excess (Scheme 7.8). 

Condensation of carbonyl compounds. This magnesium phenolate catalyzes the self-condensation of linear aliphatie aldehydes. When the reaction is conducted in HMPT, 1,3-diol monoesters (3 and 4) are formed (equation I). When the reaction is conducted in benzene, 2,3-dialkylacrylaldehydes (5) are formed, also in high yield (equation II). Magnesium ions (MgBr and Mg ) are much more effective in these reactions than Li or Na . ... 

The mixed Tishchenko reaction involves the reaction of the aldol prodnct 113 from one aldehyde with another aldehyde having no a-hydrogens to yield an ester The products were proposed to be formed through an aldol step (equation 33), followed by addition of another aldehyde (equation 34) and an intramolecular hydride transfer (equation 35). However, several aspects of this mechanism need to be clarified. As part of the continuing mechanistic studies carried out by Streitwieser and coworkers on reactions of alkali enolates ", it was found that the aldol-Tishchenko reaction between certain lithium eno-lates and benzaldehyde proceeded cleanly in thf at room temperature". Reaction of the lithium enolate of isobutyrophenone (Liibp) with 1 equiv of benzaldehyde in thf at — 65 °C affords a convenient route to the normal aldol product 113 (R = R" = Ph, R = Me). At room temperature, however, the only product observed after acid workup was the diol-monoester 116, apparently derived from the corresponding lithium ester alcoholate (115, R = R" = Ph, R = Me), which was quantitatively transformed into 116 after quenching. As found in other systems", only the anti diol-monoester diastereomer was formed. 

Other olelius bearing polar atoms in the vicinity of tbe double bond that have been converted into the corresponding 1,2-dids by treatment with a peroxy add and subsequent alkaline hydro-]yei i e, 233, i27 , 1S7P are the substances shown in Eq, (751), In these instances the direction of ring fission is unfortunately not known, since 1,2-diol monoesters thereby generated were for the most part hydrolyzed directly. 

Evans, D. A., Hoveyda, A. H. Samarium-catalyzed intramolecular Tishchenko reduction of 3-hydroxy ketones. A stereoselective approach to the synthesis of differentiated anti 1,3-diol monoesters. J. Am. Chem. Soc. 1990, 112, 6447-6449. 

Olefins. Emmons and co-workers found that the anhydrous reagent in methylene chloride reacts instantly at 0° with all simple olefins tried it is much more reactive than performic acid. Higher terminal olefins react rapidly, whereas with performic acid at 40° the reaction takes 8-24 hrs. The initially formed epoxide is cleaved by CF3CO2H to the diol monoester, and this is converted into the diol by methanolysis. In initial experiments the monoester reacted to some extent with the epoxide, but this side reaction is inhibited by adding triethylammonium trifluoroacetate to increase the effective concentration of trifluoroacetate ion. Example a solution... 

The alternative method of reduction of such hydroxyketones is the a //-selective Evans intramolecular delivery of nucleophilic hydride through a cyclic transition state. In Janda s bryostatin synthesis, the diol monoester 182, produced by kinetic resolution with an immobilised lipase (chapter 29) is reduced to the an//-diol 183 by acetoxy-borohydride. The hydride delivery is intramolecular through a chair transition state 184. This is 1,3-control via a cyclic transition state (chapter 21).30... 

Trimethylphenoxymagnesium bromide catalyzes aldol condensation of aliphatic aldehydes to form a,3 unsaturated aldehydes in excellent yield if the reaction is carried out in benzene (Scheme 1). In hexamethylphosphoric triamide (HMPA), the diol monoesters (1) and (2) are produced, also in nearly quantitative yield. Compounds (1) and (2) arise from a process known as the Tischtschenko reaction vide infra). 

Allylic substitution. Catalyzed by CuCl, the reaction of RZnBr (R = aryl, alkenyl) with cfr-4-cyclopentene-l,3-diol monoesters proceeds regioselectively along an Sn2 pathway to provide trani -2-substituted 3-cyclopentenols. 

Trioxanes bearing a hydrogen substituent at C(3) are also cleaved by base, but more slowly. Exposure of the c -fused bicyclic trioxanes (83) and (85) to triethylamine in methylene chloride for 9 days at 25°C affords the 1,2-diol monoesters (84) and (86) in 67-78% yield (Equation (7)) <85CC1783>. The resulting diol has the cw-configuration, the same as that of the starting trioxane. 

This reaction has been extended to other cyclic and open-chain 1,2-diol monoesters. ... 

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