Crystal‐Packing‐Driven Enrichment of Atropoisomers

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.

A Three‐Dimensional Dynamic Supramolecular “Sticky Fingers” Organic Framework

“…Therefore, the formation of dynamic structures (porous or non‐porous acting as porous) by means of supramolecular interactions between molecules might be an interesting alternative. However, the crystallization of stable organic structures possessing porosity or showing the ability to incorporate molecules by internal structural reorganization (breathing effect) is still a real challenge, with some examples reported using hydrogen bonding or π–π stacking as a driving force.…”

“…[11] MOFs offer improved flexibility compared to rigid zeolites and less processable COFs. [12] This flexibility could generate novel dynamic adsorption properties under realistic conditions-similar to the liquid-protein reactions that occur for specific interactions between an enzymatic host and as ubstrate.P ure organic systems usually demonstrate excellent properties,s uch as high thermal stabilities,t unable structural properties,a nd biocompatibility;h owever,t hey also present drawbacks,s uch as rigidity and limited processability.T herefore,t he formation of dynamic structures (porous or non-porous acting as porous) by means of supramolecular interactions between molecules might be an interesting alternative.H owever,t he crystallization of stable organic structures possessing porosity or showing the ability to incorporate molecules by internal structural reorganization (breathing effect) is still areal challenge,with some examples reported using hydrogen bonding [8,[13][14][15][16][17][18][19][20][21][22] or p-p stacking [8,[23][24][25] as adriving force.In this manuscript, we report for the first time how af lexible non-porous organic molecule connected through supramolecular van der Waals interactions,s o-called "sticky fingers", [26] behaves as an excellent dynamic molecular receptor.F urthermore,t he inclusion of small molecules inside this material allows an unprecedented hydrogenation reaction that occurs only in ac onfined crystalline space and not by traditional wet chemistry.The reaction is performed in as ingle-crystal-to-single-crystal (SCSC) fashion, which has allowed us to study how this material behaves upon the inclusion of these small molecules with atomic detail. [27] To study this process we have used one of the most versatile organic molecules,n amely the [60]fullerene.T hese highly functionalized [60]fullerene cycloadducts are very appealing scaffolds for the construction of 3D crystalline materials because of the directionality of their malonate substituents.…”

“…[11] MOFs offer improved flexibility compared to rigid zeolites and less processable COFs. [12] This flexibility could generate novel dynamic adsorption properties under realistic conditions-similar to the liquid-protein reactions that occur for specific interactions between an enzymatic host and as ubstrate.P ure organic systems usually demonstrate excellent properties,s uch as high thermal stabilities,t unable structural properties,a nd biocompatibility;h owever,t hey also present drawbacks,s uch as rigidity and limited processability.T herefore,t he formation of dynamic structures (porous or non-porous acting as porous) by means of supramolecular interactions between molecules might be an interesting alternative.H owever,t he crystallization of stable organic structures possessing porosity or showing the ability to incorporate molecules by internal structural reorganization (breathing effect) is still areal challenge,with some examples reported using hydrogen bonding [8,[13][14][15][16][17][18][19][20][21][22] or p-p stacking [8,[23][24][25] as adriving force.…”

A Three‐Dimensional Dynamic Supramolecular “Sticky Fingers” Organic Framework

“…[1] In chemistry,t his usually translates into highly selective reactions with high rates and efficiencies. [12] This flexibility could generate novel dynamic adsorption properties under realistic conditions-similar to the liquid-protein reactions that occur for specific interactions between an enzymatic host and as ubstrate.P ure organic systems usually demonstrate excellent properties,s uch as high thermal stabilities,t unable structural properties,a nd biocompatibility;h owever,t hey also present drawbacks,s uch as rigidity and limited processability.T herefore,t he formation of dynamic structures (porous or non-porous acting as porous) by means of supramolecular interactions between molecules might be an interesting alternative.H owever,t he crystallization of stable organic structures possessing porosity or showing the ability to incorporate molecules by internal structural reorganization (breathing effect) is still areal challenge,with some examples reported using hydrogen bonding [8,[13][14][15][16][17][18][19][20][21][22] or p-p stacking [8,[23][24][25] as adriving force.In this manuscript, we report for the first time how af lexible non-porous organic molecule connected through supramolecular van der Waals interactions,s o-called "sticky fingers", [26] behaves as an excellent dynamic molecular receptor.F urthermore,t he inclusion of small molecules inside this material allows an unprecedented hydrogenation reaction that occurs only in ac onfined crystalline space and not by traditional wet chemistry.The reaction is performed in as ingle-crystal-to-single-crystal (SCSC) fashion, which has allowed us to study how this material behaves upon the inclusion of these small molecules with atomic detail. In that sense,p orous materials connected by intermolecular bonds (such as,m etal-organic frameworks [6] (MOFs), covalent organic frameworks [7] (COFs), or porous molecular materials [8] that are built from discrete molecules [9] such as porous organic cages) [10] have provided notable results.The discovery and development of these materials has spurred an interest in confined chemical reactions to determine how spatial confinement can influence the yields and reactivity pathways of reactions.…”

“…In that sense,p orous materials connected by intermolecular bonds (such as,m etal-organic frameworks [6] (MOFs), covalent organic frameworks [7] (COFs), or porous molecular materials [8] that are built from discrete molecules [9] such as porous organic cages) [10] have provided notable results.The discovery and development of these materials has spurred an interest in confined chemical reactions to determine how spatial confinement can influence the yields and reactivity pathways of reactions. [12] This flexibility could generate novel dynamic adsorption properties under realistic conditions-similar to the liquid-protein reactions that occur for specific interactions between an enzymatic host and as ubstrate.P ure organic systems usually demonstrate excellent properties,s uch as high thermal stabilities,t unable structural properties,a nd biocompatibility;h owever,t hey also present drawbacks,s uch as rigidity and limited processability.T herefore,t he formation of dynamic structures (porous or non-porous acting as porous) by means of supramolecular interactions between molecules might be an interesting alternative.H owever,t he crystallization of stable organic structures possessing porosity or showing the ability to incorporate molecules by internal structural reorganization (breathing effect) is still areal challenge,with some examples reported using hydrogen bonding [8,[13][14][15][16][17][18][19][20][21][22] or p-p stacking [8,[23][24][25] as adriving force. [12] This flexibility could generate novel dynamic adsorption properties under realistic conditions-similar to the liquid-protein reactions that occur for specific interactions between an enzymatic host and as ubstrate.P ure organic systems usually demonstrate excellent properties,s uch as high thermal stabilities,t unable structural properties,a nd biocompatibility;h owever,t hey also present drawbacks,s uch as rigidity and limited processability.T herefore,t he formation of dynamic structures (porous or non-porous acting as porous) by means of supramolecular interactions between molecules might be an interesting alternative.H owever,t he crystallization of stable organic structures possessing porosity or showing the ability to incorporate molecules by internal structural reorganization (breathing effect) is still areal challenge,with some examples reported using hydrogen bonding [8,…”