SYNTHESIS BASED ON CYCLOHEXADIENES - PART 25 - TOTAL SYNTHESIS OF (+ -)-ALLO-CEDROL (KHUSIOL)/

The first stereoselective total synthesis of (+/-)-allo-cedrol 20, an enantiomer of khusiol and a complex sesquiterpene having a novel tricy clo[5.2.2.0(1,5)]undecane framework, is reported from 8-methoxytricycl o[6.2.2.0(1,6)]dodec-6-en-9-one 6c. The methodology involves preparati on of 9-methoxytricyclo[7.2.1.0(1,6)]dodec-6-en-8-one 12 from 6c and i ts conversion through the compounds imethyl-9-methoxytricyclo[7.2.1.0( 1,6)]dodec-5-ene 38, hoxy-2,6,6-trimethyltricyclo[6.2.1.0(1,5)]undecan e 48 into 2,6,6-trimethyltricyclo[6.2.1.0(1,5)]undecan-7-one 49. Witti g reaction of 49 affords the olefin 50 which has been smoothly rearran ged into khusione 51. Metal-ammonia reduction of khusione under specif ic conditions affords (+/-)-allo-cedrol. Thus, bridgehead substitution of a methoxy group by a methyl group is the key reaction in this synt hesis. In an alternative strategy, attempted conversion of oxy-2-methy ltricyclo[6.2.1.0(1,5)]undec-5-en-7-one 16 into khusione 37 results in an inseparable mixture of the isomers. A notable observation in this synthesis is the unusual formation of a gamma-alkylated product 27 dur ing Woodward methylation of 16.