C/s-hydrindanes

Intramolecular Michael addition. Stork and co-workers have examined a route to c/s-hydrindanes by intramolecular Michael addition rather than vinylo-gous aldol condensation. Thus the 3,4-disubstituted cyclohexenone 1 undergoes Michael addition rather than aldol condensation when treated with K2CO3 at 20° (40 hours the reaction is hindered by the 8-methyl group). The method should be general. 

In order to obtain high enantioselectivities it seems to be important that the reactions proceed via cationic intermediates (e.g. 24) to disfavor the partial dissociation of the chiral ligand. For this reason, silver salts are added to reactions of vinyl-iodides. These reactions are best performed in Al-methylpyrrolidone (NMP) as a solvent. As the examples shown in Scheme 9 demonstrate, both c/s-decalin [12] and cA-hydrindane [13] derivatives can be obtained in useful yields and enantiomeric purities. 

A further advantage of the c/s-oriented 4,6 Claisen rearrangement is the stereospecific alkylation of decalin and hydrindane systems4 9 420. Further examples are reported in refs 167. 240 and 421-425. 

Hydrindanes have the five-membered ring in the envelope conformation with the six-membered ring in a chair. The c/s-indane (241) shows a 1,3-diaxial Rl—H interaction and one of the bridgehead hydrogens interacts with the two R groups, giving another gauche- i]/.e. interaction (similar to Corey s G values) Another... 

The application of nonenzymic biogenetic-like olefinic cyclizations for the stereospecific construction of polycyclic systems, developed by W. S. Johnson and his school, represents an exciting new approach to steroid total synthesis. The synthesis of progesterone, outlined below, is based on the finding that an appositely placed acetylenic bond participates in polyolefinic cyclizations directly to produce the C/D trans-fused hydrindane system... 

---