Taxol asymmetric dihydroxylation

Amino-Hydroxylation. A related reaction to asymmetric dihydroxylation is the asymmetric amino-hydroxylation of olefins, forming v/c-ami noalcohols. The vic-hydroxyamino group is found in many biologically important molecules, such as the (3-amino acid 3.10 (the side-chain of taxol). In the mid-1970s, Sharpless76 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.77... 

Several methods have been developed for the synthesis of the taxol side chain. We present here the asymmetric construction of this molecule via asymmetric epoxidation and asymmetric ring-opening reactions, asymmetric dihydroxylation and asymmetric aminohydroxylation reaction, asymmetric aldol reactions, as well as asymmetric Mannich reactions. 

Wang et al.36 have used the chiral catalyst (DHQ)2 PHAL (see Chapter 4 for the structure) for the asymmetric synthesis of the taxol side chain. Optically enriched diol was obtained at 99% ee via asymmetric dihydroxylation. Sub-... 

Recently Lee and his collaborators reported a new route to the /3-lactam taxol side chain precursor through a /3-bromo amide (249). Thus, Sharpless asymmetric dihydroxylation of a cinnamide gave the diol 7.1.18 in 94-96% ee. After converting the diol to /3-bromo amide 7.1.19, treatment with TBAF or NaH gave the /3-lactam 7.1.20 in 93-94% yield without significant loss of optical purity. 

As an alternative functional group to an epoxide, cyclic sulfates and sulfites have also been used as intermediates to prepare the taxol side chain. Thus, asymmetric dihydroxylation of cis methyl cinnamate using AD-mix (3 gave the diol 7.2.12, which was converted to the cyclic sulfate... 

Prize in Chemistry. (The other half of the 2001 prize was awarded to W. Knowles and R. Noyori for their development of catalytic asymmetric reduction reactions see Section 7.14A.) The following reaction, involved in an enantioselective synthesis of the side chain of the anticancer drug paclitaxel (Taxol), serves to illustrate Sharpless s catalytic asymmetric dihydroxylation. The example utilizes a catalytic amount of K20s02(0H)4, an OSO4 equivalent, a chiral amine ligand to induce enan-tioselectivity, and NMO as the stoichiometric co-oxidant. The product is obtained in 99% enantiomeric excess (ee) ... 

The Sharpless catalytic asymmetric dihydroxylation reaction has found countless applications in synthesis, of which only a few illustrative examples are discussed. The enantioselective synthesis of the side chain 318 of the anticancer agent paclitaxel (Taxol, 320) has attracted much interest. Its preparation was accomplished on a mole-scale by Sharpless through the use of... 

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