Significance of Conformational Analysis in the Computational Studies of the reactions in a Flexible Substrate: Tandem C-C Coupling and C-H Activation Reaction of a Diene

We carried out an extensive computational study on the Pd catalyzed intramolecular Heck reaction and C-H activation of a brominated diene resulting in a fused cyclopentane. As the substrate is flexible, we have used conformational search, clustering analysis, and modeling to select eight conformations for studying the catalytic cycle. Coordination of the catalyst (PdPPh3) on the re and si faces of substrate gave rise to 16 complexes. The bidentate coordination from both the double bonds of the substrate is found to be more stable than the monodentate coordination. Migratory insertion is the regioselective, 5-exo versus 6-endo cyclization, step. The selectivity is correlated with the unique geometric features of the intermediates; in the twisted orientation, Pd–C1 and C5–C6 bonds are perpendicular to each other and can facilitate 5-exo and 6-endo cyclization, while the eclipsed orientation where these bonds are parallel can only undergo 5-exo cyclization. The 5-exo routes from eclipsed orientations have mu...