title: Regioselectivity of intermolecular Pauson-Khand reaction of aliphatic alkynes: experimental and theoretical study of the effect of alkyne polarization.
abstract: Generally judged poor electronic regioselectivity of alkyne insertion in intermolecular Pauson-Khand reaction (PKR) has severely restricted its synthetic applications. In our previous rational study concerning diarylalkynes (Fager-Jokela, E.; Muuronen, M.; Patzschke, M.; Helaja, J. J. Org. Chem. 2012, 77, 9134-9147), both experimental and theoretical results indicated that purely electronic factors, i.e., alkyne polarization via resonance effect, induced the observed modest regioselectivity. In the present work, we substantiate that the alkyne polarization via inductive effect can result notable, synthetically valuable regioselectivity. Computational study at DFT level was performed to disclose the electronic origin of the selectivity. Overall, the NBO charges of alkynes correlated qualitatively with regioisomer outcome. In a detailed computational PKR case study, the obtained Boltzmann distributions of the transition state (TS) populations correlate closely with experimental regioselectivity. Analysis of the TS-structures revealed that weak interactions, e.g., hydrogen bonding and steric repulsion, affect the regioselectivity and can easily override the electronic guidance.
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, University of Helsinki , A. I. Virtasen aukio 1, P.O. Box 55, University of Helsinki FIN-00014, Finland.
authors.forename: Erika
authors.initials: E
authors.lastname: Fager-Jokela
authors.forename: Mikko
authors.initials: M
authors.lastname: Muuronen
authors.forename: Héléa
authors.initials: H
authors.lastname: Khaizourane
authors.forename: Ana
authors.initials: A
authors.lastname: Vázquez-Romero
authors.forename: Xavier
authors.initials: X
authors.lastname: Verdaguer
authors.forename: Antoni
authors.initials: A
authors.lastname: Riera
authors.forename: Juho
authors.initials: J
authors.lastname: Helaja
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008962:Models, Theoretical; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000480:Alkynes