Crystal-Packing-Driven Enrichment of Atropoisomers |
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Authors: | Mona Sharafi Joseph P Campbell Dr Sinu C Rajappan Natavan Dudkina Dr Danielle L Gray Dr Toby J Woods Prof Jianing Li Prof Severin T Schneebeli |
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Institution: | 1. Department of Chemistry, The University of Vermont, Burlington, VT, 05405 USA;2. George L. Clark X-Ray Facility & 3M Materials Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL, 61801 USA |
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Abstract: | Crystal-packing forces can have a significant impact on the relative stabilities of different molecules and their conformations. The magnitude of such effects is, however, not yet well understood. Herein we show, that crystal packing can completely overrule the relative stabilities of different stereoisomers in solution. Heating of atropoisomers (i.e. “frozen-out” conformational isomers) in solution leads to complex mixtures. In contrast, solid-state heating selectively amplifies minor (<25 mole %) components of these solution-phase mixtures. We show that this heating strategy is successful for compounds with up to four rotationally hindered σ bonds, for which a single stereoisomer out of seven can be amplified selectively. Our results demonstrate that common supramolecular interactions—for example, methyl⋅⋅⋅π] coordination and C−H⋅⋅⋅O] hydrogen bonding—can readily invert the relative thermodynamic stabilities of different molecular conformations. These findings open up potential new avenues to control the folding of macromolecules. |
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Keywords: | hydrogen bonding methyl⋅⋅⋅π interactions polymorphic transformations solid-state isomerizations thermodynamic reaction control |
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