Desogestrel, synthesis

An ethynylcerium reagent was effectively utilized in the last step for the total synthesis of desogestrel 17.12 Desogestrel was isolated in 92% yield from the corresponding ketone 16, bearing acidic a-protons (Equation (2)). 

Corey, E. J., Huang, A. X. A Short Enantioselective Total Synthesis of the Third-Generation Oral Contraceptive Desogestrel. J. Am. Chem. Soc. 1999, 121,710-714. 

Scheme 1-13 Collection of formulae relevant to a synthesis of (—)-desogestrel 40 opened by the asymmetric Hajos-Parrish-Eder-Sauer-Wiechert reaction.

Zeelen, A partial synthesis of desogestrel based upon intramolecular oxidation of an ll/3-hydroxy-19-norsteroid. Reel. 

When mixed with alkylcopper reagents (MeCu or r-BuCu are the most common), DIBAL-H gives selective 1,4-reduction of conjugated carbonyl compounds. An example, taken from Corey s synthesis of desogestrel, is the conversion of 189 to 190 in 91 % yield, using HMPA as a solvent.220 DIBAL-H is also an effective reagent for the reduction of nitriles to aldehydes, as in the reduction of 191 to 192 in 72% yield221... 

Corey has recently proposed a total synthesis, which gives in 14 stages en-antiomerically pure desogestrel in remarkably high yields. [60] This laboratory synthesis is still a long way from an industrial process (see the red markings), but it includes some synthetically interesting steps. 

The Corey group has utilized these catalysts for a number of natural product synthesis, including estrone [35, 36], desogestrel [35], oseltamivir (Tamiflu) [37], dolabellatrienone and dolabellatriene [38], aflatoxin B2 [39], laurenditerpenol [40], and various others [41]. 

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