Crystal-packing forces can have asignificant impact on the relative stabilities of different molecules and their conformations.T he magnitude of such effects is,h owever,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." frozenout" conformational isomers) in solution leads to complex mixtures.I nc ontrast, solid-state heating selectively amplifies minor (< 25 mole %) components of these solution-phase mixtures.W es how that this heating strategy is successful for compounds with up to four rotationally hindered s bonds,for which as ingle stereoisomer out of seven can be amplified selectively.Our results demonstrate that common supramolecular interactions-for example,[ methyl···p]c oordination and [C À 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.Solid-state reactions offer [1] ap owerful alternative to solution-phase transformations with often unique [1d, 2] selectivity patterns.T hese distinct selectivities arise for different reasons,depending on whether asolid-state reaction is under kinetic or thermodynamic control. Under kinetic control, the product distributions are governed [1a-h] primarily by the relative orientations of the reactive functional groups in the solid starting materials and transition states.Awell-known example in this regard are [2+ +2]-photocycloadditions, [3] which often proceed [4] with very high regio-and stereochemical control in the solid state.O nt he other hand, for solid-state reactions under thermodynamic control, af undamentally different, less studied mode of reaction control starts to rule. It operates [5] by selectively producing the most stable solidstate supramolecular structure as the major product.To our knowledge,the magnitude of such effects has been limited [5,6] to the solid-state amplification of specific compounds already present in at least 50 mole %atequilibrium in solution. Furthermore,previous studies investigating selective solid-state reactions under thermodynamic control have been focused (Scheme 1) on atropoisomers with only one [5a,b] (Scheme 1a)o rt wo [5c] (Scheme 1b)r otationally hindered s bonds (highlighted in red in Scheme 1). In one of the first such studies (Scheme 1a), Pincock and Wilson resolved [5a] racemic,p olycrystalline biphenyl into one of its atropoenantiomers via solid-state heating. This finding has stimulated the field of spontaneous absolute asymmetric synthesis [7] significantly.More recently,this discovery has also been extended [5c] to the solid-state diastereoselection of pairs of atropodiastereoisomers (Scheme 1b). These pioneering prior reports thus demonstrated that crystal packing forces can indeed shift solution phase equilibria to more strongly favor an already preferred (! 50 mole %) solution-phase stereoisomer in the solid state.