Bridgehead hydroxyl groups

Two marine natural products, capnellene diol (129) and isoamijiol (130), were viewed as ideal candidates upon which to explore these ideas [55]. As illustrated, both of these materials incorporate a bridgehead hydroxyl group and an exocyclic carbon-carbon /i-bond, subunits which are produced as a natural consequence of the methodology. 

C NMR confirmed the presence of the bridgehead hydroxyl group through the typical quaternary carbon at 693.8 ppm, and an extra secondary hydroxyl group by the presence of four... 

Annulation reactions are possible when a precursor monocyclic substrate contains an activated alkene in a tether [4a]. As demonstrated in Scheme 5, an ester was employed to activate the olefin appended to cycloalkanone 17. Upon generation of the 0-stannyl ketyl with tributyltin hydride, the carbon-centered radical attacks the electron-poor /(-position on the activated alkene. The corresponding cyclized adduct 18 is a bicyclic skeleton with a bridgehead hydroxyl group. An example of this reaction shows cyclopentanone 19 undergoing cyclization to diquinane 20 and tricycle 21 (76 24) in 69% yield. The presence of reasonable amounts of the minor, yet readily isolable, jn-diastereomers in the reaction indicated that the reaction may not be reversible. 

A hydroxyl group has been introduced at the bridgehead of the bicyclic compound (146) by treating the carbanion with the reagent oxodiperoxy-molybdenum hexamethylphosphoric triamide, pyridine (MoOPH), to give compound (147) (81TL2341). 

During the enantioselective total synthesis of miroestrol by E.J. Corey and co-workers, the introduction of a hydroxyl group was required at one of the bridgehead positions. This position was a to a ketone and was also the allylic position to a double bond. The oxidation was effected by selenium dioxide/fert-butyl hydroperoxide at 25 °C. 

The directing effect of a hydroxyl group alpha to the bridgehead carbon was also observed with an oxabicyclo[3.2.1] substrate, although only f-BuLi is sufficiently reactive to induce ring opening, Eq. 180 [213]. 

The Clemmensen reduction of 6-oxocamphor (225), in addition to providing information about the mechanism of the Clemmensen reduction of 1,3-diketones, leads to an interesting bridgehead-hydroxylated isocamphanone (226) probably having an exo-methyl group, via the route shown. 

Reaction initiation can be achieved by dissociation of the C—O bond in (Z)-5-cyclodecenyl-paranitrobenzoate (1). The (Z)-olefin is transformed into the c/.v-decalin system 2 exclusively with the hydroxyl group and adjacent bridgehead hydrogen having an anti configuration52. 

A /ran.s-hydroazulene system is generated by reacting 6-methyI-2,6-cyclodecadienyl-l-paranitrobenzoate in aqueous acetone, The allylic carboniunt ion intermediate is attacked by the nucleophilic (Ej-olefin and the remaining tertiary cation is hydrolyzed. The hydroxyl group is placed syn to the adjacent bridgehead substituent56. 

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