title: Resolution and Determination of the Absolute Configuration of a Twisted Bis-Lactam Analogue of Tröger's Base: A Comparative Spectroscopic and Computational Study.
abstract: The first reported twisted bis-lactam, a racemic Tröger's base (TB) analogue (2), was resolved into its enantiomers on a chiral stationary phase HPLC column. The absolute configuration of (+)-2 was determined to be (R,R)-2 by comparing experimental and calculated vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectra. The absolute configuration of (-)-2 was determined by comparing experimental and calculated electronic circular dichroism (ECD) spectra. The corresponding theoretical spectra were calculated using the lowest energy conformation of (R,R)-2 and (S,S)-2 at the B3LYP/6-31G(d,p) level of theory. The absolute configuration of (+)-2 was also determined to (R,R)-2 by anomalous X-ray diffraction (AXRD) in a chiral space group P212121 using Cu-irradiation resulting in a very low Flack parameter of -0.06(3), despite the heaviest element being an oxygen atom, thus unambiguously confirming the results from the spectroscopic studies. We conclude that, for the Tröger's base (TB) analogue (2), we may rank the reliability of the individual methods for AC determination as AXRD ≫ VCD > ECD, while the synergy of all three methods provides very strong confidence in the assigned ACs of (+)-(R,R)-2 and (-)-(S,S)-2.
authors.affiliation: †Centre for Analysis and Synthesis, Department of Chemistry, Lund University, P.O. Box 124, SE-221 00, Lund, Sweden.
authors.forename: Ögmundur Vidar
authors.initials: ÖV
authors.lastname: Rúnarsson
authors.affiliation: ‡Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Str. 1, D-53121, Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Benkhäuser
authors.affiliation: §Department of Chemistry, Building 201, Technical University of Denmark, 2800 Kgs, Lyngby, Denmark.
authors.forename: Niels Johan
authors.initials: NJ
authors.lastname: Christensen
authors.affiliation: †Centre for Analysis and Synthesis, Department of Chemistry, Lund University, P.O. Box 124, SE-221 00, Lund, Sweden.
authors.forename: Josep Artacho
authors.initials: JA
authors.lastname: Ruiz
authors.affiliation: †Centre for Analysis and Synthesis, Department of Chemistry, Lund University, P.O. Box 124, SE-221 00, Lund, Sweden.|⊥Department of Chemistry, Queen's University, Kingston, ON K7L 3N6, Canada.
authors.forename: Erhad
authors.initials: E
authors.lastname: Ascic
authors.affiliation: ∥Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri 65211, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Harmata
authors.affiliation: ⊥Department of Chemistry, Queen's University, Kingston, ON K7L 3N6, Canada.
authors.forename: Victor
authors.initials: V
authors.lastname: Snieckus
authors.affiliation: #Department of Chemistry, Nanoscience Centre, University of Jyvaskyla, P.O. Box 35, FI- 40014, Jyvaskyla, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Rissanen
authors.affiliation: §Department of Chemistry, Building 201, Technical University of Denmark, 2800 Kgs, Lyngby, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Fristrup
authors.affiliation: ‡Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Str. 1, D-53121, Bonn, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Lützen
authors.affiliation: †Centre for Analysis and Synthesis, Department of Chemistry, Lund University, P.O. Box 124, SE-221 00, Lund, Sweden.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wärnmark