Enantio-complementary

The /M ) )-nitrite (or formate) esters of v/c-diols obtained via enzymatic ring-opening of epoxides in presence of nitrite (or formate) are unstable and undergo spontaneous (nonenzymatic) hydrolysis to furnish the corresponding diols. This protocol offers a useful complement to the asymmetric hydrolysis of epoxides. Depending on the type of substrate and the enzymes used, enantio-complementary epoxide hydrolysis can be achieved [1851]. 

Larissegger-Schnell, B., Glueck, S.M., Kroutil, W., and Faber, K. (2006) Enantio-complementary deracemiza-tion of ( )-2-hydroxy-4-phenylbutanoic add and (+)-3-phenyllactic acid using lipaseotalyzed kinetic resolution combined with biocatalytic racemization. Tetrahedron, 62 (12), 2912-2916. 

To prevent interference by ChiroCLEC, the acyl carrier intended for phosphine activation (the mixed mesitoate anhydride 212) was placed on an insoluble solid support where it can be accessed by the soluble phosphine, but not by the insoluble ChiroCLEC. Under three phase conditions, interference was prevented because the phosphine does not activate vinyl pivalate, the acyl donor intended for activation by ChiroCLEC in the form of an activated ester 214 nor does the activated acylphosphonium species 213 come into contact with the ChiroCLEC. Potential destruction of the lipase catalyst is thereby avoided, and the enantio-complementary activated intermediates convert the racemic alcohol R,S)-7 into the solid phase-bound ester 215 and the soluble pivalate 216 with excellent enantioselectivity. This is a proof-of-concept experiment that demonstrates the most difficult application, the case where two similar catalytic reactions are conducted in parallel. Furthermore, the experiment demonstrates PKR with the incorporation of achiral subunits to achieve enantiodivergence, and achieves product separation by simple filtration. 

Under conditions of thermodynamic control the enantio-complementary nature of the FruA-RhuA biocatalyst pair enables construction of mirror image products 78 and ent-78 from racemic 3-hydroxybutanal 77 with similar selectivity, but preference for opposite enantiomers [25]. The all-equatorial substitution in the predominant product can facilitate its separation by crystallization so that the remaining mixture can be re-subjected to further equilibration to maximize the yield of the preferred isomer 78 [177]. This general technique has recently found an application in a novel approach for the de novo synthesis of 4,6-dideoxy sugars such as 4-deoxy-r-fucose 81 or its trifluoromethylated analog (Figure 5.37) [25]. 

Biohydrolytic kinetic resolutions of racemic-PGE. Use of enantio-complementary wild-type and evolved mutant EHs for the preparation of two antipodes of PGE. 

For the syntheses of a large number of deoxypolypropionates requiring a,o -diheterofunctional intermediates, a couple of novel protocols, that are complementary with the conventional protocol using so-called Roche ester, have been developed (Scheme 33).199,200 More recently, the combined use of the ZACA reaction and the lipase-catalyzed kinetic resolution via selective acetylation has been shown to be practically attractive for the synthesis of enantio-merically pure compounds that cannot be readily purified by ordinary chromatography or recrystallization199,201 (Scheme 34). 

Carbon-carbon bond-forming reactions are of central importance in synthetic organic chemistry. Although a host of asymmetric transition metal-catalyzed (5) and organocatalyzed (6) reactions of this type are known, enzyme catalysts are often complementary and sometimes even superior. Aldolases allow the synthesis of many complex carbohydrates in one or two steps, with enantio- and diastereoselectivity... 

Discussion Taddol-catalyzed DA reactions provide simple and direct routes to functionalized cyclohexenones in enantiomerically enriched form. As with the HDA reactions, the best results were obtained when pure diene and dienophile were used, and the reaction temperature was rigorously maintained. Traces of moisture or acid impact negatively upon diene stability and product enantio-purities. One important advantage of the method is the commercial availability of both taddol catalyst 119 and the diene. The best substrates for the taddol-catalyzed DA reactions were a-substituted acroleins. This reactivity profile is complementary to that found for the secondary amine-based organocatalysis developed by MacMillan and co-workers, in which -substituted acroleins provided the best results [116]. 

A very recent study presented by Dujardin et al. describes the complementary use of chiral enol ethers as dienophiles in oxa Diels-Alder reactions. This approach has yielded promising results with regard to the synthesis of enantio-merically pure carbohydrates [481]. Further noteworthy studies directed to the preparation of biologically active amino sugars from enaminoketones have been carried out in our group [110]. 

A remarkable feature of the Evans process is its ability to mediate enantio-, chemo-, and diastereo-selective additions to 1,2-diketones (Eq. (8.18)). The Cu(II) and Sn(Il) bisoxazoline complexes display superb group selectivity, differentiating between ethyl and methyl groups in the addition of thiopropionate-derived Z-silyl ketene acetal to 84. As discussed above, the Cu(II) and Sn(ll) catalysts elicit complementary simple diastereoselectivity with the Cu(II) catalyst leading to the for-... 

An enantioseparation in this mode is based on the formation of non-covalent diastereomer-ic complexes between the enantiomers of an analyte and the chiral additive in the mobile phase (CAMP). Compared with indirect enantioseparations, the CAMP technique has advantages such as the absence of a derivatization step or a higher flexibility (easier change of a chiral additive than a chiral or an achiral packing material). As documented by Davan-kov [105], the enantiomer migration order with CAMP most likely will be opposite to that observed with the same chiral selector as the stationary phase. The complementary enantio-selectivity of enantioseparation with CAMP compared with CSPs is a significant advantage. 

Hashimoto, Y., Iwanami, N Fujimori, S., Shudo, K. (1993b). Enantio- and meso-DNAs Preparation, characterization, and interaction with complementary nucleic acids, J. Am. Chem. Soc., 115 9883. 

The four enzymes of the family of dihydroxyacetone phosphate (DHAP)-dependent aldolases fructose-1,6-bisphosphate aldolase (FruA, EC 4.1.2.13), fuculose-1-phosphate aldolase (FucA, EC 4.1.2.17), rhamnulose-1-phosphate aldolase (RhuA, EC 4.1.2.19) and tagatose-1,6-bisphosphate aldolase (TagA, EC 4.1.2.40), catalyze in vivo the reversible asymmetric addition of DHAP to d-glyceraldehyde-3-phosphate (G3P) or L-lactaldehyde, leading to four complementary diastereomers. DHAP-dependent aldolases create two new stereogenic centers, with excellent enantio and diastereoselectivity in many cases. These enzymes are quite specific for the donor substrate DHAP, but accept a wide range of aldehydes as acceptor substrates. There are only two fructose-6-phosphate aldolase isoenzymes reported to be able to use dihydroxyacetone (DHA) as donor substrate (Schiirmann and Sprenger 2001). 

Even in lipophilic solvents where hydrophobic effects and interactions are minimized, the cryptophanes strongly, reversibly and selectively complex neutral guests of complementary size such as the halogenomethanes. For example, enantio-selective complexation of CHFClBr by (140) has also been reported (138a). The water-soluble cryptophane (141) scavenges trace amounts of halogenomethanes from water. 

A complementary functional cyclopropane assembly relies on the utilization of the Tsuji-Trost reaction [101], A highly enantio and diastereoselective cou-pling/cyclopropanation sequence of acyclic amides 85 with allyl carbonates 86 is illustrated in Scheme 5.30 [102], In this reaction, a scarcely described addition of the nucleophilic enolate intermediate onto the central carbon of the i-allyl palladium is involved, which affords the corresponding cyclopropane. 

An impressive array of new catalysts for enantioselective homologation have been reported. Carlos F. Barbas 111 of Scripps/La Jolla has found (Angew. Chem. Int. Ed. 2007, 46, 5572) that the commercial amino acid 3 mediated the addition of dibydroxyacetone 2 to an aldehyde such as 1 to give the triol 4 with high enantio- and diastereocontrol. Takashi Ooi ofNagoya University has devised (J. Am. Chem. Soc. 2007,129, 12392) the catalyst 6 for the anti addition (Henry reaction) of nitro alkanes such as 5 to aldehydes. Takayoshi Arai of Chiba University has developed (Organic Lett. 2007, 9, 3595) a complementary catalyst (not shown) that mediated syn addition. Jonathan A. EUman of the University of California, Berkeley has uncovered (J. Am. Chem. Soc. 2007,129,15110) the catalyst 10 for the aza-Henry reaction. Yian Shi of Colorado State University has found (J. Am. Chem. Soc. 2007,129,11688) hgands for Pd that direct the absolute sense of the addition of 13 to dienes such as 12. 

Simeo, Y. and Faber, K. (2006) Selectivity enhancement of enantio- and stereo-complementary epoxide hydrolases and chemo-enzymatic deracemization of (+)-2-methylglycidyl benzyl ether. Tetrahedron Asymmetry, 17,402-409. 

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