Gibberellin methylenation

Gibberellin A5 (C H Os) has a melting point of 260-61° and forms a methyl ester (m.p. 190-91°). The infrared spectra of Nujol mulls of the acid and ester (see Table II) show the presence of alcoholic hydroxyl, hydroxyl of carboxylic acid, unconjugated five-ring lactone, carboxyl (or ester) carbonyl, exocyclic methylene group, and a cis-disubstituted double bond. Catalytic hydrogenation of the methyl ester confirmed the presence of two double bonds. 

Methylenation. The species obtained from the reaction of TiCl4 with zinc in < II iBr, and THF is the reagent of choice for methylenation of the gibberellin ketones I and 2, which undergo marked epimeri/ation at the adjacent chiral center on... 

The non-basic nature of the reagent makes it useful 1n other applications. It has, for example, also proved useful for the methylenation of the gibberellin norketone4 (Table I) without the need for protection of the readily epimerized 36-OH. The use of CD Br24 allows the introduction of =CD2 without scrambling of the label. 

This reaction provided a key step in a stereocontrollcd total synthesis of r/Z-gibberellin A, 4 (3). Thusreactionoftheenone(l) with cxcessdiethylaluminumcyanidein methylene chloride at room temperature gave the C/D cij-cyano ketone (2) in 87% yield. Note... 

Irradiation of the a -unsaturated ketone derived by manganese dioxide oxidation of methyl gibberellate, affords, in the solid state, a dimer in which addition of the unsaturated ketone across the terminal methylene group has occurred. Photolysis in solution leads to addition of the solvent to the unsaturated ketone. Some interest has centred on the partial synthesis of gibberellin Ajg (105), whose total synthesis was reported earlier. Details of the conversion of gibberellin A g into some 5-lactones related to gibberellin A15, and on the partial synthesis of gibberellin Ajg nor-ketone from 7-hydroxykaurenolide, reported... 

A simple route to the tetracarbocyclic skeleton of the gibberellins which possesses the advantage of generating both the bridgehead hydroxy-group and the terminal methylene of the bicyclo[3,2,l]octane system has been described. ... 

Indeed, the reproducibility of this method was questioned by Lombardo in 1982 [14]. He attempted to apply Takai and Oshima s procedure to the methylenation of a gibberellin derivative with Zn (pure, without lead)-CH2Br2-TiCl4, but only decomposition of the substrate was observed. Lombardo later demonstrated an improved procedure. According to his report, the requisite ageing period for the preparation of the reagent was three days (Scheme 5.7). 

Scheme S.7. Methylenation of a gibberellin derivative by Lombardo s method.

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