title: Rotationally Hindered Biphenyls and Terphenyls: Synthesis, Molecular Dynamics, and Configurational Assignment.
abstract: Sterically hindered naphthalene-substituted biphenyls and terphenyls were synthesized in good yields, by Michael addition of a conjugate base of core-substituted phenylacetones to substituted 2-oxo-2H-pyran-3-carbonitriles at room temperature under alkaline conditions. These diversely functionalized benzenes (1,2-teraryls or 1,3-teraryls), bearing naphthyl and substituted aryl rings, show the phenomenon of atropisomerism, with one or two stereogenic biaryl axes. The resolution of the respective four atropisomers of the naphthalene-substituted biphenyls and terphenyls bearing 1,2-type or 1,3-type chiral biaryl axes was achieved by HPLC on a chiral phase. The absolute stereostructures of 6a and 9a were determined by the combination of experimental electronic circular dichroism (ECD) investigations and quantum-chemical circular dichroism (QC-CD) calculations. For the atropisomerization of (1M,6M)-6a and (1M,5M)-9a to their (M,P)- and (P,M)-diastereomer, respectively, the possible transition states were investigated and the interconversion barriers (ΔG‡) were theoretically predicted. This study provides a general protocol for the synthesis, resolution, and stereochemical characterization of rotationally hindered naphthalene-substituted biphenyls and terphenyls. The strategy may be applied to investigate other, similarly hindered biaryl or teraryl systems either derived from natural sources or prepared through synthetic approaches.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute , Lucknow, Uttar Pradesh 226031, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Goel
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute , Lucknow, Uttar Pradesh 226031, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Institute of Organic Chemistry, University of Würzburg , Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Hemberger
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute , Lucknow, Uttar Pradesh 226031, India.
authors.forename: Fateh V
authors.initials: FV
authors.lastname: Singh
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute , Lucknow, Uttar Pradesh 226031, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Nag
authors.affiliation: Institute of Organic Chemistry, University of Würzburg , Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Knauer
authors.affiliation: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute , Lucknow, Uttar Pradesh 226031, India.
authors.forename: Ruchir
authors.initials: R
authors.lastname: Kant
authors.affiliation: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute , Lucknow, Uttar Pradesh 226031, India.
authors.forename: Resmi
authors.initials: R
authors.lastname: Raghunandan
authors.affiliation: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute , Lucknow, Uttar Pradesh 226031, India.
authors.forename: Prakas Ranjan
authors.initials: PR
authors.lastname: Maulik
authors.affiliation: Institute of Organic Chemistry, University of Würzburg , Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bringmann