title: Spontaneous transfer of chirality in an atropisomerically enriched two-axis system.
abstract: One of the most well-recognized stereogenic elements in a chiral molecule is an sp(3)-hybridized carbon atom that is connected to four different substituents. Axes of chirality can also exist about bonds with hindered barriers of rotation; molecules containing such axes are known as atropisomers. Understanding the dynamics of these systems can be useful, for example, in the design of single-atropisomer drugs or molecular switches and motors. For molecules that exhibit a single axis of chirality, rotation about that axis leads to racemization as the system reaches equilibrium. Here we report a two-axis system for which an enantioselective reaction produces four stereoisomers (two enantiomeric pairs): following a catalytic asymmetric transformation, we observe a kinetically controlled product distribution that is perturbed from the system's equilibrium position. As the system undergoes isomerization, one of the diastereomeric pairs drifts spontaneously to a higher enantiomeric ratio. In a compensatory manner, the enantiomeric ratio of the other diastereomeric pair decreases. These observations are made for a class of unsymmetrical amides that exhibits two asymmetric axes--one axis is defined through a benzamide substructure, and the other axis is associated with differentially N,N-disubstituted amides. The stereodynamics of these substrates provides an opportunity to observe a curious interplay of kinetics and thermodynamics intrinsic to a system of stereoisomers that is constrained to a situation of partial equilibrium.
authors.affiliation: Department of Chemistry, Yale University, PO Box 208107, New Haven, Connecticut 06520-8107, USA.
authors.forename: Kimberly T
authors.initials: KT
authors.lastname: Barrett
authors.affiliation: Department of Chemistry, Yale University, PO Box 208107, New Haven, Connecticut 06520-8107, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Metrano
authors.affiliation: Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania 19081-1397, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Rablen
authors.affiliation: Department of Chemistry, Yale University, PO Box 208107, New Haven, Connecticut 06520-8107, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Miller
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry*; D001966:Bromine / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D007700:Kinetics; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012399:Rotation; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D001549:Benzamides; D004364:Pharmaceutical Preparations; D002244:Carbon; D001966:Bromine
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