SYNTHESIS OF POLYPROPIONATE FRAGMENTS CONTAINING TERTIARY-ALCOHOL MOIETIES - CROSS-ALDOLISATIONS WITH LITHIUM ENOLATES OF 7-OXABICYCLO[2.2.1.]HEPTAN-2-ONE DERIVATIVES

The Diels-Alder adduct of 2,4-dimethylfuran to 1-cyanovinyl (1'R)-camp hanate ,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1'R)-campha nate ((+)-1)) was converted into (+)-2,7-dideoxy-2,4-di-C-methyl-L-gly cero-((+)-6) and -D-glycero-L-altro-heptono-1,4-lactone ((+)-7), into (-)-(3R,4R, -bis(isopropylidenedioxy)-4,6-dimethylheptan-2-one ((-)-22 ), and into :5,6-bis(isopropylidenedioxy)-2,4-dimethylheptanal ((+)-34 ). Condensation of (+)-34 with the lithium enolate of -1,5-endo-dimeth yl-7-oxabicyclo[2.2.1]heptan-2-one ((-)-38; derived from (+)-1) gave a 3:2 mixture of aldols (+)-39 and (+)-40 (mismatched pairs of a alpha- methyl-substituted aldehyde and (E)-enolate) whereas the reaction of(/-)-34 with (+/-)-38 gave a 10:1 mixture of aldols (+/-)-41 and (+/-)- 39. A single aldol, (-)-44, was obtained on condensing (+)-34 with the lithium enolate of -1,5-endo-dimethyl-7-oxabicyclo[2.2.1]heptan-2-one ((+)-43; derived from (-)-(1S,2R,4S)-2-exo-cyano-1, abicyclo[2.2.1]he pt-5-en-2-endo-yl(1'S)-camphanate ((-)-3)). All these cross-aldolisati ons are highly exo-face selective for the bicyclic ketones. The best s tereochemical matching is obtained when the lithium enolates and alpha -methyl-substituted aldehydes can realize a 'chelated transition state ' that obeys the Cram and Felkin-Anh models (steric effects). Polyprop ionate fragments containing eleven contiguous stereogenic centres and tertiary-alcohol moieties are thus prepared with high stereoselectivit y in a convergent fashion. The chiral auxiliaries ((1R)- and (1S)-camp hanic acid) are recovered at the beginning of the syntheses.