Fluorinated kaurenoids. Part 2. Preparation of methyl ent-17,17,17-trifluorokaur-15-en-19-oate and ent-16,16-difluoro-17-norkauran-19-oic acid from xylopic acid

Abstract

An attempt to convert methyl ent-16-oxo-17-norkauran-19-oate (3), derived from xylopic acid, into methyl ent-17,17-difluorokaur-16-en-19-oate failed. However, treatment of the norketone (3) with diethylaminosulphur trifluoride (DAST) gave methyl ent-16,16-difluoro-17-norkauran-19-oate (5). The latter afforded the corresponding acid (4) which was active as a growth promoter in a dwarf-rice bioassay. Treatment of methyl deacetylxylopate (18) with DAST, followed by cleavage of the terminal methylene group, yielded methyl ent-15-fluoro-16-oxo-17-norkauran-19-oate (15), which on reaction with dibromodifluoromethane and tris(dimethylamino)phosphine gave, not the expected 17,17-difluoro-olefin (19), but methyl ent-17,17,17-trifluorokaur-15-en-19-oate (28) in poor yield. Reduction of methyl xylopate with di-imide gave the 16β-methyl compound (24) stereospecifically. The latter was readily converted into methyl 15-oxokauranoate (26), but steric hindrance prevented the reaction of the oxo-group with DAST to give the 15,15-difluoride, under normal reaction conditions; using a much longer reaction time a trace of the gem-difluoride was formed.

During reduction of the dithiocarbonate (27) of methyl deacetylxylopate with tri-n-butyltin hydride into the isomeric methyl kaurenoates (8) and (31), the 17-thiol ester (32) was also formed by a [3,3]sigmatropic rearrangement.