Crystal-Packing-Driven Enrichment of Atropoisomers

Mona Sharafi, Joseph P. Campbell, Sinu C. Rajappan, Natavan Dudkina, Danielle L. Gray, Toby J. Woods, Jianing Li, Severin T. Schneebeli

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)7097-7101
Number of pages5
JournalAngewandte Chemie - International Edition
Volume56
Issue number25
DOIs
StatePublished - Jan 1 2017

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Keywords

  • hydrogen bonding
  • methyl⋅⋅⋅π interactions
  • polymorphic transformations
  • solid-state isomerizations
  • thermodynamic reaction control

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

Sharafi, M., Campbell, J. P., Rajappan, S. C., Dudkina, N., Gray, D. L., Woods, T. J., Li, J., & Schneebeli, S. T. (2017). Crystal-Packing-Driven Enrichment of Atropoisomers. Angewandte Chemie - International Edition, 56(25), 7097-7101. https://doi.org/10.1002/anie.201701876