Rotationally Hindered Biphenyls and Terphenyls: Synthesis, Molecular Dynamics, and Configurational Assignment

• Published in: Journal of organic chemistry Vol. 81; no. 22; pp. 10721 - 10732
• Main Authors: Goel, Atul, Kumar, Vijay, Hemberger, Yasmin, Singh, Fateh V, Nag, Pankaj, Knauer, Michael, Kant, Ruchir, Raghunandan, Resmi, Maulik, Prakas Ranjan, Bringmann, Gerhard
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 18.11.2016; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ATROPISOMERS; STEREODYNAMICS; ABSOLUTE-CONFIGURATION; ZETA VALENCE QUALITY; DIMERIC NAPHTHYLISOQUINOLINE ALKALOIDS; OPTICAL-PROPERTIES; BASIS-SETS; DENSITY-FUNCTIONAL THEORY; CHIRAL MOLECULES; EXCITED-STATES
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.6b01804

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.