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Crystal‐Packing‐Driven Enrichment of Atropoisomers
Author(s) -
Sharafi Mona,
Campbell Joseph P.,
Rajappan Sinu C.,
Dudkitavan,
Gray Danielle L.,
Woods Toby J.,
Li Jianing,
Schneebeli Severin T.
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201701876
Subject(s) - chemistry , hydrogen bond , supramolecular chemistry , crystal (programming language) , molecule , macromolecule , folding (dsp implementation) , crystallography , phase (matter) , crystal engineering , solid state , crystal structure , chemical physics , organic chemistry , biochemistry , electrical engineering , computer science , programming language , engineering
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.