3.3- difluoro-3-phenylpropanoic acid

Oxazolidine 130 is a masked aldimine bearing a chiral N-(2-hydroxy-l-phenyl)ethyl moiety and is readily available from (R)-phenylglycinol. Mannich reaction of 130 with Reformatsky reagent of ethyl bromodifluoroacetate produces difluorolactam 131 in high diastereoselectivity, which is then transformed to enantio-enriched (S)-3-amino-2,2-difluoro-3-phenylpropanoic acid 133 (see Scheme 9.28) [55]. 

Uoto et al synthesized a number of 2 -deoxy-2 -(difluoro)docetaxel derivatives. The parent compound 8.6.6 was prepared by coupling 7,10-(di-Troc)-lO-deacetylbaccatin III with 3-(r-butoxycarbonylamino)-2,2-difluoro-3-phenylpropanoic acid in the presence of di-2-pyridylcarbo-nate and DMAP. In an in vitro study using P388 tumor cells, 8.6.6 had a GI50 value of 21.0ng/mL compared with 30.4ng/mL for taxol 329). 

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