Self reproduction of chirality

Morigaki, K., Dallavalle, S., Walde, P, Colonna, S., and Luisi, P. L. (1997). Autopoietic self-reproduction of chiral fatty acid vesicles. /. Am. Chem. Soc., 119, 292-301. 

A special methodology has been described for the enantioselective a-alkylation of tryptophan, which is related to the principle of self reproduction of chirality (see Section 1.1.1.3.2.2.). The tryptophan derivative TO is converted to 11 which is methylated in 95% yield to one single diastereomer 12. The latter is quantitatively transformed to the methylated tryptophan IS143. 

Using the same principle as that described for l,3-dioxolan-4-ones, it is possible to a-alkylate 2-amino acids without racemization76,78. An A. O-acetal is formed from an (7 )-amino acid 1, e.g., with trimethylacetaldehyde (R2 = -Bu) the l,3-oxazolidin-5-ones 2 and 3 are furnished with a defined diastereoselectivity, which is the first stage in the process of self-reproduction of chirality 82. Formation of the enolate 4 from 2 and attack of an electrophile in the second step gives the product 6 with retention of configuration in the a-position, and 7 with inversion of configuration, again with a defined diastereoselectivity. Hydrolysis yields the a-alkylated amino acids 10 and 11. 

The term self-reproduction of chirality has been introduced to describe a process where a center of chirality in a compound is used to induce the formation of a new, second chirality center, which subsequently functions as an auxiliary . Thus, reaction at the first center destroys its chirality, whereupon a second reaction regenerates it through the influence of the chirality at the second center which bears the bulky auxiliary. This auxiliary is subsequently removed1,2. 

Side Note 13.4. An Enolate Alkylation with Self-Reproduction of Chirality ... 

The lactic acid, which initiates the reaction sequence. S -lactic acid —> acetal A — enolate B —> acetal C —> R hydroxy carboxylic acid D, has a stereocenter with a well-defined absolute configuration that is destroyed in the enolate intermediate B, but finally restored in the hydroxycarboxylic acid C. This is why the principle concerning the stereochemistry of the key step ( acetal A —> enolate B —> acetal C) is referred to as the self-reproduction of chirality. ... 

Synthesis of Unnatural (S)-Proline Derivatives. The condensation of pivaladehyde with (S)-proline yields stereoselec-tively, after lithiation and reaction with an electrophile, the hi-cyclic compound (28), which is a versatile educt for the synthesis of many a-suhstituted proline analogs (29) (eq 12). The reactions proceed via the formation of a chiral lithium enolate without the use of a chiral auxiliary (self-reproduction of chirality). The reaction with a variety of electrophiles cis to the t-Bu group yields a plethora of a-substituted (5)-proline derivatives (29). A limitation of this strategy is the acetal cleavage of some substituted products (28). ... 

As will be described below, self-reproduction of chirality can be accomplished through alkylations of endocyclic as well as exocyclic enolates. It generally entails (i) production of a ring containing a temporary, auxiliary chiral center by derivatization of an optically active a-hydroxy or a-amino ester (ii) formation of an enolate by deprotonation at the original asymmetric a-carbon atom (iii) use of intramolecular chirality transfer to control the stereochemistry of alkylation of the enolate and (iv) generation of the chiral a-alkylated ester by hydrolysis. 

Alkylation of lactates is not possible directly, since any enolate formation would destroy the chirality at the asymmetric center. This can be circumvented without use of a chiral auxiliary by employing the self-reproduction of chirality approach of Seebach, which incorporates lactic acid into a dioxolane ring and takes advantage of the bulky R group at the newly formed stereo center at C-2 to direct alkylation to the C-5 carbon. 

Among the available methods for the stereoselective synthesis of quaternary proline analogues (7)/ the direct a-functionalisation of (5 )-proline-derived oxazolidinone 5 proposed by Seebach et al. in 1983 has been extensively used in the last thirty years for the production of many bioactive compounds (Scheme 11.1)/ Both a-allq lation and a-condensation reactions proceed stereoselectively with retention of configuration, exemplifying the concept of self-reproduction of chirality . More recently, Germanas and coworkers introduced the cheaper oxazolidinone 6, derived from the condensation of (S)-proline 1 with trichloroacetaldehyde (Scheme 11.1). ... 

Morigaki et al. (25) have described the autopoietic self-reproduction of chiral fatty acids with the aim... 

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