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Nature. 2014 May 1;509(7498):71-5. doi: 10.1038/nature13189. Epub 2014 Apr 20.

Spontaneous transfer of chirality in an atropisomerically enriched two-axis system.

Author information

1
Department of Chemistry, Yale University, PO Box 208107, New Haven, Connecticut 06520-8107, USA.
2
Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania 19081-1397, USA.

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.

PMID:
24747399
PMCID:
PMC4008667
DOI:
10.1038/nature13189
[Indexed for MEDLINE]
Free PMC Article

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