Stereoselective alcoholysis

Several monofunctional and bifunctional cinchona alkaloid derivatives were successfully utilized as organocatalysts for the stereoselective alcoholysis of meso-anhydrides (for details, see Chapter 10) [65], It was also reported that the zinc complex... 

There has been considerable interest in the stereoselective ring opening of meso-cyclic anhydrides. The stereoselective alcoholysis of these anhydrides is particularly attractive as the resulting hemiesters are used as versatile intermediates in the construction of many bioactive compounds [1], Much effort has, therefore, been devoted to the development of efficient enzymatic and nonenzymatic catalytic systems for this reaction [2], Among the stereoselective catalysts developed to date,... 

Enantioselective alcoholysis of racemic, prochiral, or meso cyclic anhydrides can be catalyzed by hydrolases, yielding the corresponding monoesters (Eigure 6.25). In most cases, the enantioselectivity was moderate ]75-77]. Organometallic catalysts or organocatalysts such as cinchona alkaloids are often more efficient than enzymes for the stereoselective ring opening of cyclic anhydrides. 

The benzotriazolyl derivative of acrolein acetal, compound 882, is lithiated, treated with chlorodiphenylphosphine, and the obtained intermediate is oxidized with hydrogen peroxide to phosphine oxide 883 (Scheme 145). The relatively acidic proton in derivative 883 is easily removed by a base, and the obtained anion adds to a carbonyl group of aldehyde or ketone. Subsequent rearrangement and elimination of the phosphorane group generates diene 884. For the derivatives of aldehydes (884, R2 = H), (E)-(E) stereoselectivity of the elimination is observed. Acidic alcoholysis of dienes 884 affords esters of P,y-unsaturated carboxylic acids 885 < 1997JOC4131>. 

Olah et al.724 have shown that Nafion-H induces the ring opening of oxiranes under mild conditions to afford various products. Substituted oxiranes undergo hydrolysis or alcoholysis to yield 1,2-diols or 1,2-diol monoethers, when treated with Nafion-H under mild conditions in the presence of water or alcohols, respectively. Cycloalkene oxides give the corresponding trans products stereoselectively [Eq. (5.273)]. 

Bornane[10,2]sultams have been exploited as chiral auxiliaries for stereoselective aziridination of attached 7V-enoyl substituents28. The alkene substitution pattern markedly affected the diastereoselectivity, which was excellent when the C — C double bond was unsubstituted in this case the configuration of the prevalent diastereomer 5 was established by X-ray crystallographic analysis. Thus, the addition occurred to the Re-face at the a-carbon. In the other cases the stereochemistry of the major diastereomers was tentatively assigned by analogy. Furthermore, the yield dropped drastically when an a-substituent was present. Removal of the auxiliary was achieved by titanium isopropoxide alcoholysis, but was not optimized. No epimerization occurred during the cleavage process. 

The stereochemistry of the homogeneous rhodium-catalyzed alcoholysis reaction has also been studied (77) (eq. [52]). The predominant stereochemistry was established through a Walden cycle, reduction of the alkoxysilane 142 occurring with almost complete retention at silicon. As shown in Table 31, the rhodium-catalyzed alcoholysis occurs with retention of configuration but low stereoselectivity. Moreover, when the alcohol was used as solvent, predominant inversion or racemization was observed. Predominant inversion was also found in alcoholysis of a substituted silacyclopentane (171), but concomitant epimerization yielding the equilibrium mixture of isomers was observed. 

Mechanistic Studies.- A study has been published on the alcoholysis of a phosphonamidite (76) containing a properly positioned amino group which results in intramolecular catalysis upon protonation. 2 jhg reaction of (76) with methanol was 150-300 times faster than analogous reactions of (77), and the catalytic rate constant kc was independent of the pKa of the acid catalyst used (amine hydrochlorides), indicating that (78) is the actual catalyst. A similar chiral phosphonite (79) (mixture of two diastereomers) reacted with optically active alcohols to give phosphonites with a maximum stereoselectivity of 3 1 when an achiral amine hydrochloride was used as the catalyst. 

Bis(allyl)homoallyloxysilanes 56a and 56b are designed for a tandem intramolecular silylformylation-allylsUylation reaction, which has turned out to be an efficient approach to construct polyol and polyketide frameworks [21], For example, heating a solution of 56 in benzene at 60 °C in the presence of Rh(acac)(CO)2 under CO atmosphere followed by the Tamao oxidation gives syn,syn-triols 59 stereoselectively via oxasilacyclopentanes 57 and 58 (Scheme 5.14). Bis(ds-cro-tyl)silane 56b is readily prepared by double Pd-catalyzed 1,4-hydrosilylation of 1,3-butadiene with dichlorosilane followed by reduction with UAIH4 and alcoholysis with the corresponding homoallylic alcohol. 

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