Absfhzct. The optically active tax01 A-ring unit 3 was synthesized in 11 steps from 2-isopropyl-2-propenol. The stereogenic centers were introduced via the asymmeuic glyoxylateene reaction and the Sharpless asymmetric epoxidation reaction.
The total synthesis of tax01 (1) and analogous compounds has attracted an increasing interest due to their manifested anticancer effect.'" We reported earlier that the enantiomerically pure tax01 A-ring unit 3 could be synthesized from Larabinose (Scheme l).a'
Scheme 1
The reaction sequence was too long, however, in order to be practically useful for further development of the tax01 synthesis, although we used the small amount of material available to prepare seco-taxane 2'. This compound has all the carbon atoms required for the tax01 carbon skeleton and also many of the stemogenic centers and functionalities which makes it an interesting intermedk for further transformations; in patticu-
OTBB &Bs >99 (z-95% ee) 4
Scheme 2t2
Unfortunately, these reaction conditions applied on 514 and ethyl glyoxylate gave only traces of the ene product (Table ). Attempts with other Lewis acids such as TiC14 SnC14 Et2AlCl, BF3 . 0Et2 and AlMe$S)-BINOL's in catalytic (0.05-O. 1 mol%) and stoichiomeuic amounts were unsuccessful as well. Interestingly, despite that only traces of ene product was produced using a catalytic amount of C12Ti(OiPr)2 up to 80% yield of the expected ene product was obtained in experiments performed with 2 equiv of the Lewis acid and 5 equiv of ethyl glyoxylatc (Entries 1,2). But still only traces of the eue product was obtained using the chiral Lewis acid C12Ti(OiPr)2 / (WBINOL at the 2 equivalents level (Entry 3). It is not evident why compound 5 does not behave well in this type of reactions but a similar non-reactivity of the benzyl ether of 2-butcn-l-01 has been noted. I3 A satisfactory explanation must await further investigation.
We next turned to ene nactions with chiral glyoxylates. Achmatowicz et alI6 showed that it was possible to induce some optical activity (530% ee) iu the product formed in the ene reaction between menthyl glyoxylates and 1-penteue using various Lewis acids. More recently Whitesell et al.*7-rs improved this type of re-2709