Regio- and Stereoselective Synthesis of the 1,3-Cyclohexadiene Nucleus by [2 + 2 + 2] Cycloaddition Reactions Catalyzed by Titanium Aryloxide Compounds

A variety of titanium aryloxide reagents catalyze the cross coupling of two alkyne units with 1 equiv of olefin to produce the 1,3-cyclohexadiene nucleus. Catalysts include isolated titanacyclopentadiene or titanacyclopentane complexes. The reaction proceeds via attack of the olefin upon a titanacyclopentadiene compound initially formed by coupling of two alkyne units. The reaction is limited to bulky alkyne substrates that undergo slow catalytic cyclotrimerization via competing attack of a third alkyne upon the titanacyclopentadiene ring. The organic products isolated are typically the result of an isomerization within the initially produced 1,3-cyclohexadiene nucleus. Mechanistic studies show that these isomerization processes occur via sequential, metal-mediated 1,5-hydrogen shifts upon a single face of the six-membered ring, exclusively leading to a cis -stereochemistry within the final products. In the reactions of the diynes R C⋮C(CH 2 ) 4 C⋮C R (R = Et, SiMe 3 ), coupling with ethylene and α-olefins produces a variety of substituted hexalins. A combination of NMR spectroscopy, photochemistry, and molecular mechanics calculations has been applied to determine the stereochemistry and ground state conformations adopted by the product 1,3-cyclohexadienes and hexalins. The primary and secondary photoproducts obtained from some of these 1,3-cyclohexadiene compounds have been characterized.