Example 1
General Synthetic Procedures, Preparation of Reaction Intermediates
(R)-epichlorohydrin 5 and (S)-epichlorohydrin ent-5 were purchased from Chem Impex. Alkyne 7, alkyne 19, alkyne 22, and anhydrous methanol (MeOH) were purchased from Sigma-Aldrich, St. Louis, Mo., USA. Chloroform (CHCl3) and bromoform (CHBr3) were purchased from Alfa Aesar, Tewksbury, Mass., USA. titanium isopropoxide (Ti(Oi-Pr)4), and nitromethane (MeNO2) were purchased from Acros Organics (Pittsburgh, Pa., USA), and titanium isopropoxide was distilled before use.
The hydrindane products of Ti-mediated annulation (alkene isomers) were used in subsequent steps as mixtures (the steroidal end products of the synthesis sequence were easily separated from byproducts generated from the minor “endo” diene isomer). For characterization of the major isomers formed from Ti-mediated annulation, a small amount of each mixture (<50 mg) was purified by HPLC to obtain analytical samples. (See, the trans-fused hydrindanes: 8, ent-8, 14, 17, 20, 23, 26, 29, 32, and S16).