Chiral production level

It is imdisputed that asymmetric synthesis has gained increasing importance both at the university level and in industry. The last ten years have seen enormous advances in asymmetric catalysis using transition metals and during the next decade further progress will be made. The market for optically-pure pharmaceutical compounds grows faster than for classical fine chemicals. In 1994 bulk intermediates for pharmaceuticals reached a market volume of 9.2 billion. At the beginning of the next century the potential market for synthetic chiral products in bulk form alone is estimated to be much more. 

The addition of other sulfur nucleophiles was reported by Jacobsen to be catalyzed by the same Cr(salen) complex 1 initially reported for the ARO with TMSNj. Benzyl mercaptan afforded the ring-opened hydroxy sulfides in excellent yield and 59-70% ee [17]. The moderate levels of enantioselectivity were improved by use of the dithiol 5, which afforded mixtures of bishydroxy sulfides in which the ee of the chiral product 6 was substantially enriched (Scheme 5). The sulfide products could be easily elaborated into the free thiols by reductive de-benzylation, providing access to the jl-silyloxy thiol 8 in optically pure form. 

Jacobsen disclosed a chiral Co(salen) catalyst that promoted the hydrolytic kinetic resolution (HKR) of terminal epoxides [40]. Remarkably low levels of the Co(salen)OAc complex 12 effected enantioselective epoxide hydrolysis to afford mixtures of the unreacted epoxide and the ring-opened diol. Controlling the amount of water in the HKR allowed either of these chiral products to be generated in high enantiopurity (Tables 3 and 4) [41]. Significant differences in vola-... 

When the 1,4-reduction is taken out of equation, the 1,2-reduction occurs readily to give chiral products. With several potent ligands introduced and the conditions rigorously optimized, the asymmetric reduction with chiral CuH complexes reached the level of maturity and is ready for challenging S3mthetic application. 

Table 6.8 Production level of chiral alcohols by PAR, Sar268, and HAR1 [10],...

The production level of )-3-quinudidinol in our study was the highest ever reported, indicating an efficient NADH regenerating power of E. coli (LSADH) with I PA, and that E. coli biocatalysis would provide a practical method of produdng important chiral compounds. 

Horeau principle provides the mathematical foundation for rationahzing the enan-tioenrichment observed along successive catalytic cycles of asymmetric MCRs [7]. The simple calculations shown in Figure 42.1 reveal that this strategy can provide the major diastereomer of a chiral product that has two stereogenic centers with exquisite levels of enantiocontrol. This is despite combining two consecutive catalytic processes that might be only moderately selective (e.g., 80% ee + 80% ee = 97.5% ee). 

Optically inactive starting materials can give optically active products only if they are treated with an optically active reagent or if the reaction is catalyzed by an optically active substance The best examples are found m biochemical processes Most bio chemical reactions are catalyzed by enzymes Enzymes are chiral and enantiomerically homogeneous they provide an asymmetric environment m which chemical reaction can take place Ordinarily enzyme catalyzed reactions occur with such a high level of stereo selectivity that one enantiomer of a substance is formed exclusively even when the sub strate is achiral The enzyme fumarase for example catalyzes hydration of the double bond of fumaric acid to malic acid m apples and other fruits Only the S enantiomer of malic acid is formed m this reaction... 

The foregoing examples do not represent useful chiral formyl anion equivalents in a direct sense since the stereoselectivity of the initial addition to aldehydes is poor, although as has been explained, the situation is salvaged by oxidation and re-reduction. On the other hand, by lithiation at the 2 position of the achiral oxazo-lidine 53 in the presence of (-)-sparteine followed by addition of benzaldehyde, useful levels of d.e. and e.e. are achieved directly (98TA3125). For example, by adding MgBr2 before the benzaldehyde, the major product obtained is 54 in 80% d.e. and 86% e.e. 

In general the chiral additive (l/ ,2/J)-l,2-dimethoxy-l,2-diphenylethane was the most effective while (.S )-2.2 -diniethoxy-1,1 -binaphthalene and (1 / ,27 )-/V,/V,/V, A"-tetramethyl-1,2-diphcnyl-ethylenediamine induced only very low levels of enantiofacial differentiation. In the case of the acyclic enimines competing 1,2-addition products were also obtained7. 

Reactions of nitro compounds with chiral imines have only recently been described. Either chiral 1-phenylethylamine (auxiliary) or the glyceraldehyde acetonide aldehyde was used as the chiral precursors of the imines 66 and 68, which reacted with 3-mesyloxynitropropane to give the 3-nitropyrrolidines dl)-67 and 69, respectively, with good diastereoselectivity. In fact, both products were obtained (almost) exclusively as trans diastereomers with high level of asymmetric induction, but the configurations of the newly formed stereocenters were not determined [44] (Scheme 13). N-Boc imines can be formed... 

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