| Description |
A rapid method of constructing tricyclic cyclopentanones demonstrating good diastereoselectivity via the Nazarov cyclization was introduced. Torquoselectivity governed stereochemistry observed in the final products. Torquoselectivity is determined by steric interactions during the actual cyclization process. Starting with complex, readily available starting materials, complexity was increased quickly setting several stereocenters during the Nazarov cyclization. The commercially available bicyclo[2.2.1]heptane system in camphor and bicyclo[3.1.1]heptane system of myrtenal and nopinone were used as starting materials. These facially biased systems have unique steric environments differentiating the top and bottom faces of the molecule. In three steps, each starting material was functionalized into a variety of dienones. First, each compound was converted to a hydrazone, which was submitted to Shapiro reaction conditions, generating a dienol. Oxidation of these dienols generated the desired dienones to be cyclized under Nazarov conditions. Camphor substrates showed torquoselectivity ranging from excellent to moderate, favoring exo-type products. However, when TiCU was used to cyclize these substrates, unexpected chloride incorporation occurred. Myrtenal substrates showed torquoselectivity also, but to a lesser extent. More interestingly, the interactions present in the 3.1.1 system reverse selectivity, favoring the endo product. Many of these cyclizations not only displayed chloride trapping, but also Wagner-Meerwein shifts. Other titanium(IV) halogen Lewis Acids also furnished halogen trapped products. |
