Synthesis of the Side Chain by Sharpless Asymmetric Aminohydroxylation

Synthesis of the Side Chain by Sharpless Asymmetric Aminohydroxylation 

Sharpless catalytic asymmetric aminohydroxylation (AA) provides a direct and efficient route to the taxol side chain as well as a number of other natural products and synthetic ligands. The required asymmetry of the taxol side chain was controlled by (DHQ)2-PHAL, and hydroxyla-tion was achieved with potassium osmate (K20s02(0H)4). Various N-haloamide salts were investigated, and yields and percentage ee were good to excellent under different conditions. For example, reaction of methyl cinnamate under Sharpless catalytic AA conditions gave (2R,3S) N-tosyl-3-phenyl isoserine 7.3.1 in 82% ee in 69% yield. Compound 7.3.1 was then converted to the taxol side chain acid in two steps in good yield (262). 

Several other investigators have used the Sharpless chemistry to make the taxol side chain or analogs of it. Thus an N-benzoyl side chain was prepared in one step from rran -isopropyl cinnamate using benzamide-based AA in 60% yield with 3 1 regioselectivity and 97% ee (263). Side chains with heterocyclic rings at C-3 have been prepared by AA thus for example furan (264) and pyridine (265) analogs of the side chain have both been prepared by this method. 

The Sharpless tosylamide 7.3.2 can be converted directly to the oxazolidine 7.3.3, which can be coupled to baccatin III as described below (266). 

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