Meso-trick

The process of obtaining homochiral product from a prochiral starting material is known as asymmetrization. This encompasses reactions where a faster rate of attack of a reactive species occurs on one enantiotopic face of a prochiral trigonal biplanar system, or at one enantiotopic substituent of a C2 symmetrical system, resulting in the preferential formation of one product enantiomer. The latter is also frequently referred to as the meso-trick or desymmetrization . These transformations can be more easily defined in pictorial form (Figure 1.8). 

Some Equivalent Nonsystematic Terms (Kinetic Resolution, Meso-Trick)... 

Furthermore, a clear definition of the term meso-trick is apparently not available. Seebach13 implies that the meso-trick involves an KPC synthesis which starts with a we.vocompound that is completely transformed, via a sequence of reactions involving a stereoselective reaction or resolution, into one enantiomer. 

The ill-defined term meso-trick and the related term chiral economy should be avoided when a stereoselective reaction rather than a separation step is involved. Preferably, the well-defined term enantiotopos-differentiating reaction should be used. 

In the meso-trick the same principle is applied [25]. A symmetric compound, in this case a meso compound, is submitted to selective hydrolysis. The asymmetric compound that is generated in this manner is obtained in 100% yield and ideally high optical purity (Scheme 6.8). Meso compounds with diamino, diol or diacid functions can be converted to chiral mono-esters or mono-amides, too, if the reaction is performed in organic solvents [22, 24, 27]. 

An application of the meso trick that does not, in principle, require recycling, has been provided (Fig. 7) by a Japanese group (25). Reaction of cis-2-cyclopenten-l,4-diol [36] with W-mesyl-S-phenylalanyl chloride gave, in addition to diester and recovered starting material, the diastereo-meric esters [37] and [38]. Separation was effected by either chromatography or crystallization. Conversion of the free alcohol of [37] to its tetra-hydropyranyl ether and saponification gave alcohol [39], Transfer of the... 

In asymmetric hydrogenation generally, it is surprising how rarely the meso-trick has been employed. There is a nice example from Takehashi s work [128] involving a symmetrical divinyl alcohol. In this case both double bonds were reduced, and although the raeso-diastereomer accounted for 20% of the product, the remaining R,R-diacid (isolated as its diester) had 94% ee, giving a simple access to the core portion of an active HIV protease (Fig. 37). 

Finally, reaction E in Fig. 4 illustrates a stereoselective synthesis that proceeds by differentiation of two enantiotopically related groups of a meso compound. Here, one hydroxyl group of d.s-1,2-cyclohexanediol is preferentially benzoylated in the presence of one molar equivalent of an enantiomerically pure diamine [26]. These desymmetrization reactions (that have many biological versions) are also called meso-tricks , and are currently receiving a great deal of attention for the preparation of new chiral building blocks [27]. 

Q Meso-trick" s a term used to describe the desym-metrisation of a prochiral-ormeso-compound in order to obtain an enantiopure product In theoretically 100% yield. 

Enantiomerically pure cyclopentenones are accessible via enzyme-catalysed processes. By photochemical oxidation and acetylation, c s-l,4-diacetoxycyclo-pent-2-ene is obtained. Taking advantage of the meso-trick cf. section 5.1.3) with an enzyme from Pseudomonasfluorescens, the latter can be converted upon recrystallisation and oxidation into (R)-acetoxycyclopentenone. (The (S)-enan-tiomer is obtainable by hydrolysis with pig Ever esterase.) [221,222]... 

For enantiomericaUy pure cis-chrysanthemic acid, an enantioselective synthesis is used, which takes advantage of the abftity of microorganisms to differentiate between two enantiotopic, but chemically equivalent groups (the so called meso-trick cf. section 5.1.3). In contrast to the resolution of two enantiomers, the turnover amounts here to 100 % with an enantiomeric excess of > 98 %. The fact that the sequence starts from a cyclic compound, ensm-es that the cis-configura-tion is obtained. 

Also from Mori stems an enzymatic method for the preparation of (+)-dispar-lure. [196] With butyne-l,4-diol as the starting material, the meso-trick (cf. section 5.1.3) is used in order to generate the mono-protected diol in good yield and enantiomeric purity. The attractant is then obtained by stepwise introduction of the side-chains with lithium cuprates. 

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