Enantioselective Acylation of Alcohols

9 ENANTIOSELECTIVE ACYLATION OF ALCOHOL AND AMINE REACTIONS IN ORGANIC SYNTHESIS 

From the hydrolases toolbox, probably lipases have been the most demanding catalysts for synthetic application. Their natural funchon involves the hydrolysis of triacylglycerol ester bonds, compoimds that are poorly soluble in water. Thus, the reaction usually occurs in an organic-aqueous interface. This phenomenon involving the conformational change of the selected lipase is called interfacial achvahon [35], and it provides an inherent affinity for hydrophobic media to the enzyme. 

Hydrolases and mainly lipases have appeared as valuable biocatalysts for the development of asymmetric transformations. Several strategies have been carried out involving the classical KR and DKR of racemic alcohols and the desymmetrization of meso- and prochiral diols. Taking into account the reversibility of this type of process in complementary hydrolysis pathway and adequate conditions must be established to favor synthetic acylation reactions. 

Complementarity of acylation and hydrolysis reactions using hydrolases as blocatalysts. 

General representation of classical kinetic resolutions (a), dynamic kinetic resolutions (b), and desym-metrization processes (c). 

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The seminal work of Klibanov in the early 1980s [46,47] made it clear that enzymes can be used in hydrophobic organic solvents, although at the price of a severely reduced reaction rate [48, 49]. Indeed, many Upases, as well as some proteases and acylases, are so stable that they maintain their activity even in anhydrous organic solvents. This forms the basis for their successful application in non-hydrolytic reactions, such as the (enantioselective) acylation of alcohols and amines, which now are major industrial applications [50]. 

In the same way, Vedejs et al. [15] have explored the catalytic use of chiral phosphines in the enantioselective acylation of alcohols by the anhydrides. Moderate to good enantioselectivities were obtained using chiral phosphine 1 a as catalyst in the benzoylation of 2 a. In this case, the monobenzoate 3 a was obtained in 68% ee and 84% conversion. 

Hydrolysis of activated aryl esters, in particular nitrophenyl esters, has been used extensively to demonstrate the principles of antibody catalysis. This type of substrate is advantageous for model studies because formation of the tetrahedral intermediate is rate limiting, so that the issue of guiding decomposition of this intermediate towards hydrolysis does not need to be addressed in design. Nevertheless, hydrolyses of non-activated esters are also catalyzed by antibodies, the most notable example being that of R- and S-selective esterolyses of 2 by antibodies raised against hapten 1 (Scheme 1) [13]. Another anti-1 antibody was shown to promote enantioselective acylation of alcohols such as (S)-4 using vinyl ester 3 as acyl donor [14]. 

Acylation. The Cj-symmetric phosphine 2 is useful for enantioselective acylation of alcohols." Chiral mixed carbonates are prepared from 3 and secondary alcohols, allowing a kinetic resolution of the alcohols. ... 

Enantioselective Acylation of Alcohol and Amine Reactions In Organic Syitthesis... 

The enantioselective acylation of alcohols, and amine reactions by lipases and esterases in organic synthesis with examples of classical and dynamic kinetic resolutions of racemates, are shown, giving attention to the desymmetrization of meso-compoxmds. 

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