Abstract

The Diels-Alder adduct of 2,4-dimethylfuran to 1-cyanovinyl (1'R)-camphanate ((+)-(1R,2S,4R)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2- endo-yl (1'R)-camphanate ((+)-1)) was converted into (+)-2,7-dideoxy-2,4-di-C-methyl-L-glycero-((+)-6) and -D-glycero-L-altro-heptono-1,4-lactone ((+)-7), into (-)-(3R,4R, 5R,6S)-3,4:5,7-bis(isopropylidenedioxy)-4,6-dimethylheptan-2-one ((-)-22), and into (+)-(2R,3R,4R,5S,6S)-3,4:5,6-bis(isopropylidenedioxy)-2,4-dimethylheptan al ((+)-34). Condensation of (+)-34 with the lithium enolate of (-)-(1R,4R,5S,6R)-6-exo-[(tert-butyl)dimethylsilyloxy]-1,5-endo-dimethyl -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 (+)-(1S,4S,5S,6S)-5-exo-(benzyloxy)-1,5-endo-dimethyl-7-oxabicyclo[2.2.1 ]heptan-2-one ((+)-43; derived from (-)-(1S,2R,4S)-2-exo-cyano-1, 5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl(1'S)-camphanate ((-)-3)). All these cross-aldolisations are highly exo-face selective for the bicyclic ketones. The best stereochemical 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). Polypropionate fragments containing eleven contiguous stereogenic centres and tertiary-alcohol moieties are thus prepared with high stereoselectivity in a convergent fashion. The chiral auxiliaries ((1R)- and (1S)-camphanic acid) are recovered at the beginning of the syntheses.

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