Enantioselectivity products

Nitrilases are quite rare in bacterial genomes and less than 20 were reported prior to the application of metagenomics for their detection in environmental DNA [81]. Two studies targeting environmental genomes report the detection of more than 337 novel nitrilases. This has dramatically increased the amount of information about nitrilases, and the newly discovered diversity can be applied for the enantioselective production of hydroxy carboxylic add derivatives [81]. 

Lipase catalysis is often used for enantioselective production of chiral compounds. Lipase induced the enantioselective ring-opening polymerization of racemic lactones. In the lipase-catalyzed polymerization of racemic (3-BL, the enantioselec-tivity was low an enantioselective polymerization of (3-BL occurred by using thermophilic lipase to give (/ )-enriched PHB with 20-37% enantiomeric excess (ee). ... 

Yeom, S.-J., Kim, H.-J. and Oh, D.-K. (2007) Enantioselective production of 2,2-dimethylcyclopropane carboxylic acid from 2,2-dimethylcyclopropane carbonitrile using the nitrile hydratase and amidase of Rhodococcus erythropolis ATCC 25544. Enzyme and Microbial Technology, 41, 842-848. 

Diastereoface-differentiating reactions of a carbenoid with an alkene bearing an easily removable, chiral substituent have been used only ocassionally for the enantioselective production of a cyclopropane 216). A recent example is given by the cyclopropanation of the (—)-ephedrine-derived olefin 223 with CH2N2/Pd(OAc)2 after removal of the protecting group, (1/ , 2R )-2-phenylcyclopropane carbaldehyde was isolated with at least 90% e.e. 37). 

Bergeron S, Chaplin D, Edwards JH, Ellis BS, Hill CL, Holt-Tiffin K, Knight JR, Mahoney T, Osborne AP, Ruecroft G (2006) Nitrilase-catalyzed desym-metrization of 3-hydroxyglutaronitrile preparation of a statin side-chain intermediate. Org Proc Res Dev 10 661-665 Burns M, Weaver J, Wong J (2005) Stereoselective enzymic bioconversion of aliphatic dinitriles into cyano carboxylic acids. WO 2005100580 DeSantis G, Zhu Z, Greenberg W, Wong K, Chaplin J, Hanson SR, Farwell B, Nicholson LW, Rand CL, Weiner DP, Robertson D, Burk MJ (2002) An enzyme library approach to biocatalysis development of nitrilases for enantioselective production of carboxylic acid derivatives. J Am Chem Soc 124 9024-9025... 

Table 34.2 Selected results for the enantioselective hydrogenation of N-aryl imines 1 and 2 (for structures, see Fig. 34.4) Catalytic system, reaction conditions, enantioselectivity, productivity and activity.

Lewis acid catalysis is not limited to cases in which increased yields or enhanced selectivities are desired. Lewis acids offer also the possibility to induce chiral information leading to enantioselective product formation. The enantioselective induction by chiral Lewis acids found widespread application in organic synthesis, especially in the synthesis of natural products with many chiral centres. An enantioselective Diels-Alder reaction is the key step in the synthesis of an iodolactone prostaglandine precursor (Scheme 6).88... 

The highly enantioselective production of ( + )-(S )-benzenemethan-a-configurational determination of 8 rests on an asymmetric Meerwein-Ponndorf reduction (with isobornyloxymagnesium bromide). On mechanistic grounds the reduction of benzaldehyde-rf was assumed to produce preferentially the 7 -isomer225. 

When one of the reactants is chiral, asymmetric induction can provide enantioselective products ... 

A strategy involving a palladium-catalyzed cyclization/hydride capture process has been used in the synthesis of chiral benzofuran derivatives (Scheme 8G.15) [36], Aryl iodides 15.1 and 15.3 were cyclized under cationic conditions in the presence of HC02Na to give benzofurans 15.2 and 15.4, respectfully, both with good enantioselection. Products resulting from a 6-endo-... 

The treatment of various sulfides with Phi = NTs in the presence of cuprous triflate leads to the corresponding N-tosylsulfimides (N-tosylsulfilimines) 21 [30]. The presence of the chiral bis(oxazoline) ligand 22 in the reaction medium results in coordination of the copper(III)-nitrene intermediate, L Cu(III) = NTs, and enables the enantioselective production of 21 (Scheme 12). Similar copper-catalyzed reactions of allylic sulfides with Phi = NTs lead to formal insertion of the NTs group into the carbon-sulfur bond of the substrates, and proceed via a [2,3]-rearrangement with allylic inversion, to give sulfonamides 23 [30]. 

J. 2002. An enzyme library approach to biocatalysis development of nitrilases for enantioselective production of carboxylic acid derivatives./. Am. Chem. Soc.,124(31), 9024-9025. 

In the case of biocatalysis, enzymes [3] and catalytic antibodies [4] have attracted most attention. Since enzymes are inherently the more active catalysts, they have been used most often. Indeed, many industrial processes for the enantioselective production of certain chiral intermediates are based on the application of enzymes, as in the lipase-catalyzed kinetic resolution of an epoxy-ester used in the production of the anti-hypertensive therapeutic Diltiazem [5]. Recently, it has been noted that there seems to be a trend in industry to use enzymes more often than in the past... 

From 1988 to 1990, Ihara and co-workers modified the above synthesis approach to develop an asymmetric total synthesis of (-)-tylophorine [(-)- ] via an intramolecular double Michael reaction of a,p-imsaturated esters. Their work proved that the absolute configuration of naturally occurring (-)-tylophorine is (R). Two different chiral auxiliaries, (-)-phenylmenthol [52, 53] or (2R,4S,5R)-(-)-4-(tert-butyldimethylsiloxymethyl)-5-hydroxy-2-phenyl-1,3-dioxane(BDH), were employed [53, 54]. The reactions are summarized in Scheme (2). The resulting (E, E)-esters (26) and (27) underwent a double Michael reaction through proposed transition states (A) (B), respectively, to give a highly enantioselective product (28 and 29, respectively). (-)-... 

Musco [92] and Consiglio [93] have used palladium-oxazoline complexes (28,29) to produce styrenic copolymers that exhibit high optical rotations. Takaya has briefly noted the use of his novel phosphine-phosphite bi-dentate ligands for the enantioselective production of aromatic polyketones [82]. 

Both are stereoselective syntheses resulting from diastereoisomerically related attacks of the organometallic species on diastereotopic carbonyl faces. Reaction A generates enantiomers and results in the enantioselective production of one enantiomer over the other. Reaction B generates diastereoisomers and results in the diastereoselective production of one diaster-eoisomer over the other. The argument that the enantiotopic faces of benzaldehyde in A become diastereotopic only upon reagent complexation, whereas the 2-phenylpropanal faces in B are diastereotopic per se clearly cannot be used to classify these processes in a different way. Indeed, both reactions can be considered of type 2a according to the Mislow s classification of stereoselective processes [4]. 

Figure 4.2 Enantioselective production of syn-HT-2-anthracenecarboxylic acid dimer with AD capped y-CD. Reprinted with permission from [12], Copyright 2005 American Chemical Society...

---