Palladium 64 Sharpless dihydroxylation

Several enantioselective approaches to vitamin E (1), based on resolution of the products, the use of enantiopure natural building blocks, auxiliary controlled reactions and asymmetric oxidations have been described. In addition, a palladium-catalyzed asymmetric allylic alkylation reaction to build up the chiral chroman framework has been employed by Trost. Tietze and coworkers have developed asymmetric syntheses of the chiral chroman moiety using either the selective ally-lation of an alkyl methyl ketone or a Sharpless dihydroxylation as the key step. However, none of these methods is efficient enough for an industrial approach. ... 

Keinan prepared separately the two fragments (the THF moiety and the Y-methyl-y-lactone) and used, as a key step of his sequence, the asymmetric dihydroxylation (AD-mix.-p), the very efficient Sharpless procedure for the formation of a,(3-diols. Then, the cross-coupling was performed by addition of an alkyne and a vinyl halide in the presence of palladium and copper catalysts (Fig. 6). Treatment of the unsaturated ester 48 (prepared in 4 steps from commercially available starting material, and 65 % overall yield) with AD-mix.-p in rerr-butanol/water (1 1) with methanesulfonamide for 16 h at 0 °C afforded the lactone 49 which possessed 3 carbon atoms out of the 4 with the desired absolute configuration. Inversion of the fourth stereocentre after acetonide... 

G.4 Amino-Hydroxylation. A related reaction to asymmetric dihydroxylation is the asymmetric amino-hydroxylation of olefins, forming vic-aminoalcohols. The v/c-hydroxyamino group is found in many biologically important molecules, such as the P-amino acid 3.10 (the side-chain of taxol). In the mid-1970s, Sharpless reported that the trihydrate of N-chloro-p-toluenesulfonamide sodium salt (chloramine-T) reacts with olefins in the presence of a catalytic amount of osmium tetroxide to produce vicinal hydroxyl p-toluenesulfonamides (Eq. 3.16). Aminohydroxylation was also promoted by palladium. ... 

While the strategy developed for the synthesis of epiquinamide by Chandrasekhar et al. could in principle have produced either enantiomer of the alkaloid, the specific example reported was of the (—)-antipode, efji-2104 (Scheme 275) The flexibihty in their route is due to Sharpless asymmetric dihydroxylation of the dienoate 2179, which was prepared in four steps fi-om hexane-1,6-diol (not illustrated). With TUD-mix-a as oxidant, the (S,S)-(—)-diol 2180 was formed in 80% yield and better than 98% enantio-selectivity stereocomplementary results were obtained from AD-mix-p, which produced the enantiomeric diol (+)-eni-2180. Hydrogenation of (—)-2180 over a palladium—carbon catalyst followed by heating with potassium carbonate afforded the butyrolactone (+)-2181, the secondary alcohol of which was tosylated before rmdergoing Sn2 substitution with an azide ion to give 2182. Replacement of the TBS ether by a mesyl ester then set the... 

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