title: Mechanism and Selectivity in the Pd-Catalyzed Difunctionalization of Isoprene.
abstract: The three-component coupling of isoprene, an alkenyl triflate, and styrenylboronic acid catalyzed by a palladium pyrox complex affords access to skipped dienes from simple chemical feedstocks. Unfortunately, the transformation proceeds with only moderate selectivity and yields. The reaction mechanism and factors responsible for the resulting regioselectivity were elucidated using M06/SDD/6-311++G(d,p) + SMD calculations. Distortion of the palladium coordination sphere in the transition structure of the migratory insertion step is found to control the 4,1- vs 1,x-selectivity. The calculated ΔΔG⧧of 1.0 kcal/mol for this step is in excellent agreement with the experimentally observed selectivity of 1:9.9 disfavoring the 4,1-product. The transmetalation was found to be the regioselectivity determining step for the formation of the 1,2- vs 1,4-addition products. Systematic conformational searches for the transmetalation transition structure revealed a series of steric interactions between the t-Bu substituent on the ligand and the substrates in the model system that are balanced by additional repulsive interactions between the substrates and the pyridyl portion of the ligand. The combination of these effects leads to the low to moderate 1,2- vs 1,4-selectivity in the experimentally studied system.
authors.affiliation: Laboratory of Computational Chemistry and Drug Design, Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School , Shenzhen 518055, People's Republic of China.|School of Chemical Engineering, Shandong University of Technology , Zibo 255049, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Xu
authors.affiliation: Laboratory of Computational Chemistry and Drug Design, Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School , Shenzhen 518055, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, University of Utah , 315 S. 1400 East, Salt Lake City, Utah 84112, United States.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: McCammant
authors.affiliation: Department of Chemistry, University of Utah , 315 S. 1400 East, Salt Lake City, Utah 84112, United States.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Sigman
authors.affiliation: Laboratory of Computational Chemistry and Drug Design, Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School , Shenzhen 518055, People's Republic of China.|College of Chemistry and Molecular Engineering, Peking University , Beijing 100871, People's Republic of China.
authors.forename: Yun-Dong
authors.initials: YD
authors.lastname: Wu
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556-5670, United States.
authors.forename: Olaf
authors.initials: O
authors.lastname: Wiest