A novel construction method for the steroid skeleton such as 6,(5β)-Androstene-3,17-dione (1) by the transannular Diels-Alder reaction of macrocycles and a discussion of the diastereo-selectivity of this reaction based on MM2 transition structure models are presented. In this synthesis, transannular Diels-Alder reaction of the 14-membered diketone 3, prepared by the intramolecular alkylation of the protected cyanohydrin 14, provide all the relative stereo-chemistries among the A, B and C-rings. The trans stereochemistry between C(13)-methyl and C(14)-hydrogen in 3 is introduced by the Michael addition of the vinyl cuprate 6 to the enone 5 and subsequent β-methylation of the resulting enolate.
