Aldol condensation asymmetric synthesis involving

Both the enantiomers of Ipc2BH have been elegantly applied in the asymmetric hydroboration of safranol isoprenyl methyl ether for the synthesis of carotenoids (3R,3 R)-, (3S,3 S)-, and (3R,3 S meyo)-zeaxanthins (eq 5). (3,S,5/ ,3, S, 5 R)-Capsorubin, a carotenoid found in the red paprika Capsicum annuum, was synthesized via a key step involving asymmetric hydroboration of the unsaturated acetal followed by an aldol condensation (eq 6). ... 

We (Novartis) reported the first enantioselective synthesis of (27 ,2 7 )-(+)-f/7reo-methylphenidate hydrochloride (1), which involved an asymmetric aldol condensation of 5-chlorovaleraldehyde with the (Z)-boron enolate derived from 7V-phenylacetyl-(7 )-4-phenyl-2-oxazolidinone (29) as the key step to generate both stereogenic centers of 1 with desired absolute configuration (Scheme ll). ... 

Largely stimulated by the synthesis of 3-lactam antibiotics, there have been widespread investigations into the stereochemical aspects of imine condensations, mainly involving reactions of enolates of carboxylic acid derivatives or silyl ketene acetals. In analogy to the aldol condensation, stereoselectivity of imine condensations will be discussed in terms of two types in this chapter (i) simple dia-stereoselectivity or syn-anti selectivity, when the two reactants are each prochiral (equation 12) and (ii) diastereofacial selectivity, when a new chiral center is formed in the presence of a pre-existing chiral center in one of the reactants (e.g. equation 13). The term asymmetric induction may be used synonymously with diastereofacial selectivity when one of the chiral reactants is optically active. For a more explicit explanation of these terms, see Heathcock s review on the aldol condensation. ... 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

Finally, several other animal tissues yield useful enzymes that have been employed in S5mthesis. Pepsin is an important digestive protease from animal stomach whose native role is hydrolyzing amide bonds involving hydrophobic, aromatic amino adds, for example, phenylalanine, tyrosine, and tryptophan. Acylase from pordne kidney sdectivdy hydrolyzes N-acetyl amino adds and is commercially available. It has long been used for kinetic resolutions of amino adds. In addition to hydrolases, other animal enzymes have found important applications in biocatalysis. Rabbit musde aldolase is commerdally awiilable and was shown to catalyze aldol condensations between dihydroxyacetone phosphate and various nonnatural aldehydes by the Whitesides group in 1989 [10]. This seminal report touched off an avalanche of new applications for this and related enzymes in asymmetric synthesis. 

Aldol reactions of this type, involving 2-acetamido-2-deoxyaldohexoses, have been studied in connection with the chemical synthesis of A -acetyl-neuraminic acid (50) and related substances, and, for this reason, the choice of the dicarbonyl compound has thus far been limited to oxalacetic acid and its esters. Oxalacetic acid condenses readily with 2-acetamido-2-deoxyaldohexoses in aqueous solution at pH 11. Under these conditions, acetamido sugars partially epimerize, and the aldol reaction takes place for both of the 2-acetamido-2-deoxyaldohexoses present. The complexity of the reaction is further increased by the formation of asymmetric centers at carbon atoms 3 and 4 of the condensation products, namely, diacids (45) and (48), and this can result in the formation of four diastereo-isomers from each sugar. The reaction using 2-acetamido-2-deoxy-o-rnannose (47) has been the one most extensively studied. In this... 

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