SummaryThe first steps of a novel approach to the total synthesis of 9,ll-dehydroestrone via tricyclo [3.3.0.02~8]octan-3-one (2) are described. One route involves a tandem-type transformation of the key intermediate 3 (A-CD unit) consisting of cyclopropane cleavage and ring B closure to afford C, 18-bisnor-13 a, 17 a-estradiol derivatives. E.g. the 3-methoxy-9 <-hydroxy-17 a-methanesulfonyloxy derivative (-)-6 has been synthesized in 8 steps and 10% overall yield from 1,3-cyclohexadiene. As an alternative, the A-CD type intermediate 4b has been prepared and could be used for a ring C enlargement prior to cyclization.In a recent review we have presented a new polyvalent concept for the synthesis of cyclopentanoid natural products based on tricyclo [3.3.0.0z~8]octan-3-one (2, Scheme 1 ) as a versatile building block [2]. The enantiomers of 2 are accessible in high chemical yields and in optical purities of > 98% [2] [3].The basic requirements to be met for a competitive synthesis directed towards 9,lldehydroestrone, estrone and functionalized derivatives, have been discussed in the context of recent literature [2]. Our tricyclooctanone route can also be adapted to the synthesis of potential precursors of ring C-functionalized steroids (e.g. 8-and 9,lldehydroestrone) following the A-CD -+ABCD build-up principle [2]: (-)-6 (enantiomeric excess > 98%) is thus accessible in only 8 synthetic manipulations and in 10 % yield starting from 1,3-cyclohexadiene. We now present experimental details of this and on a number of related transformations demonstrating further the versatility of the tricyclooctanone approach. The feature common to these transformations is that all involve a single operational step which includes the cleavage of the three-membered ring and the formation of ring B in a tandem-type process.') Presented in part at the 29th IUPAC Congress, Koln 1983 [l]; see also the recent review [2]
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