Enantioselective synthesis substrate selection

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

The results shown in Scheme 6 are representative and point out which ligand provides the highest selectivity for a particular substrate (<2% SN2 product in all cases). The catalytic enantioselective synthesis of quaternary carbons represents a unique and effective method for the regio- and enantioselective prepa-... 

An important further development came from the group of Tietze, who introduced the concept of silyl termination in order to control the regio-selectivity of the final fl-H elimation step in the case of substrates (63) with R = H [20]. An example is the transformation shown in Scheme 17, a key step in an enantioselective synthesis of a cytostatic nor-sesquiterpene [20c]. 

When it became clear that the two IS-enantiomers of metolachlor were responsible fijr most of the biological activity (see Fig. 1), there was the obvious challenge of finding a chemically and economically feasible production process for the active stereoisomers. Many methods allow the enantioselective synthesis of chiral molecules (that is the preferential formation of one enantiomer instead of the usual racemate). However, the selective preparation of S-metolachlor was a formidable task, due to the very special structure and properties of this molecule and also because of the extremely efficient production process for the racemic product as described above. During the course of the development efforts, the following minimal requirements evolved for a technically viable catalytic system ee S80%, substrate to catalyst ratio (s/c) >50 000 and turnover fi-equency (tof) >10 000 h" . 

Hashimoto also developed an enantioselective synthesis of 3-arylindan-l-ones (54, Fig. 4) [69], Although the yields were excellent for these reactions (92-96%), the highest enantioselectivity achieved was only 72% with Rh2(5 -PTTL)4. In 2001, Doyle and May reported that aryldiazoacetates are quite selective substrates for... 

The production of enantiomerically pure chemicals is one of the more demanding and important challenges in chemical research, both at fundamental and at applied levels. Enantioselective synthesis and racemate separation rely on specific interactions between a chiral phase and a substrate. Thus, molecular modeling may be applied to the design of new, highly efficient, chiral phases that are able to selectively... 

As is usually the case, however, specific results are dependent on the substrate in question, and the selectivity observed a case of both steric and electronic factors. For example, in their enantioselective synthesis of (-)-pinidine, Momose et al. reported a highly diastereoselective reaction employing the reagent derived from 1,1-diiodoethane and diethyl zinc. Substrate 45 was selectively converted to stereoisomer 46 in excellent yield. 

Medic CA, Zechman AL. Selectivity in rhodium(II) catalyzed reactions of diazo compounds effects of catalyst electrophiKcity, diazo substitution, and substrate substitution. From chemoselectivity to enantioselectivity. Synthesis. 2003 35 1137-1156. 

Phosphoric acid 25a was successfully employed for mediating enantioselective synthesis of 1,3-disubstituted isoindolines from electrophilic bifunctional substrates (containing an imine and a Michael acceptor site) and indoles [33]. Catalyst 7a was used effectively in an organocatalytic asymmetric F-C alkylation/cyclization cascade reaction between 1-naphthols and a,(i-unsaturated aldehydes to give chro-manes in good yields and select vities (Scheme 3 5.18) [ 10]. Furthermore, 2-naphthols and p,y-unsaturated a-keto ester also reacted in a F-C alkylation/dehydration sequence, in the presence of a thiourea catalyst and a catalytic amount of concentrated sulfuric acid, affording optically active naphthopyran derivatives [54]. 

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