Synthesis of Cyclically Protected Side Chains

Early on in the study of the synthesis of taxol from baccatin III it was realized that the C-13 hydroxyl group of baccatin III is very hindered, so that acylation by a bulky protected side chain is difficult. One of the favored approaches to overcoming this problem is to protect the 2 -hydroxyl group through a cyclic structure, usually as an oxazolidine or an oxazoline. The synthesis of these protected side chains thus becomes an important goal. 

Inspired by their earlier synthesis of chiral 4-methoxy-2-oxazolidi-nones, Kunieda et al accomplished a synthesis of the docetaxel side chain 

Following the original report that the oxazoline carboxylic acid 7.5.12 can serve as an excellent side chain precursor 281), several syntheses of this compound have been reported. Thus racemic oxazoline was prepared from protected cinnamyl alcohol by addition of phenyl-selenyl triflate and azide ion to give the adduct 7.5.9, which was then converted to oxazoline 7.5.10 and ester 7.5.11 282). A similar but more efficient route used diphenyldiselenide and ammonium persulfate to give the racemic oxazoline 7.5.10 in 95% yield from cinnamyl acetate 283). 

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