Correlation of Intermolecular Acyl Transfer Reactivity with Noncovalent Lattice Interactions in Molecular Crystals: Toward Prediction of Reactivity of Organic Molecules in the Solid State

Intermolecular acyl transfer reactivity in several molecular crystals was studied, and the outcome of the reactivity was analyzed in the light of structural information obtained from the crystals of the reactants. Minor changes in the molecular structure resulted in significant variations in the noncovalent interactions and packing of molecules in the crystal lattice, which drastically affected the facility of the intermolecular acyl transfer reactivity in these crystals. Analysis of the reactivity vs crystal structure data revealed dependence of the reactivity on electrophile···nucleophile interactions and C–H···π interactions between the reacting molecules. The presence of these noncovalent interactions augmented the acyl transfer reactivity, while their absence hindered the reactivity of the molecules in the crystal. The validity of these correlations allows the prediction of intermolecular acyl transfer reactivity in crystals and co-crystals of unknown reactivity. This crystal structure–reactivity correlation parallels the molecular structure–reactivity correlation in solution-state reactions, widely accepted as organic functional group transformations, and sets the stage for the development of a similar approach for reactions in the solid state

Correlation of Intermolecular Acyl Transfer Reactivity with Noncovalent Lattice Interactions in Molecular Crystals: Toward Prediction of Reactivity of Organic Molecules in the Solid State

Intermolecular acyl transfer reactivity in several molecular crystals was studied, and the outcome of the reactivity was analyzed in the light of structural information obtained from the crystals of the reactants. Minor changes in the molecular structure resulted in significant variations in the noncovalent interactions and packing of molecules in the crystal lattice, which drastically affected the facility of the intermolecular acyl transfer reactivity in these crystals. Analysis of the reactivity vs crystal structure data revealed dependence of the reactivity on electrophile···nucleophile interactions and C–H···π interactions between the reacting molecules. The presence of these noncovalent interactions augmented the acyl transfer reactivity, while their absence hindered the reactivity of the molecules in the crystal. The validity of these correlations allows the prediction of intermolecular acyl transfer reactivity in crystals and co-crystals of unknown reactivity. This crystal structure–reactivity correlation parallels the molecular structure–reactivity correlation in solution-state reactions, widely accepted as organic functional group transformations, and sets the stage for the development of a similar approach for reactions in the solid state

Reactivity controlled by lattice interactions in crystal: intermolecular acyl transfer in (±)-2,4-di-O-benzoyl-myo-inositol 1,3,5-orthoformate

(±)-2,4-Di-O-benzoyl-myo-inositol 1,3,5-orthoformate, on heating in the presence of a base, undergoes transesterification to give 2,4,6-tri-O-benzoyl-myo-inositol 1,3,5-orthoformate and 2-O-benzoyl-myo-inositol 1,3,5-orthoformate in the solid state. The same reaction can also be performed by microwave irradiation instead of heating. The crystal structure of the dibenzoate reveals that the screw-axis-related molecules have the hydroxyl and the carbonyl groups ideally oriented for the reaction and gives a close picture of how such a reaction proceeds in enzymes. The structure of the corresponding acetate, (±)-2-O-benzoyl-4-O-acetyl-myo-inositol 1,3,5-orthoformate, lacks this geometry and hence is unreactive in the solid state. Both the acetate and the benzoate undergo base-catalyzed transesterification in solution

Helical Preorganization of Molecules Drives Solid-State Intermolecular Acyl-Transfer Reactivity in Crystals: Structures and Reactivity Studies of Solvates of Racemic 2,6-Di‑<i>O</i>‑(4-fluorobenzoyl)-<i>myo</i>-inositol 1,3,5-Orthoformate

Racemic 2,6-di-<i>O</i>-(4-fluorobenzoyl)-<i>myo</i>-inositol 1,3,5-orthoformate yielded structurally dissimilar solvent-free and solvated crystals depending upon the solvent of crystallization. The solvated crystals exhibited helical assembly of host molecules, due to the interaction of the guest molecules with the orthoformate moiety of the host. Some of the solvates showed specific but incomplete benzoyl group transfer reactivity below the phase transition temperature, whereas the reaction in solvent-free crystals led to a mixture of several products. These results reveal the necessity of helical molecular packing of the reacting molecules in their crystals to facilitate specific intermolecular acyl transfer reactivity. The crystal structures of the fluorobenzoate solvates were similar to those of the solvates of the analogous chloro and bromobenzoates. The latter could be thermally transformed into their solvent-free form via melt crystallization, resulting in the conversion of a helical molecular packing into a nonhelical molecular packing

Synthesis of the Aminocyclitol Units of (−)-Hygromycin A and Methoxyhygromycin from <i>myo</i>-Inositol

Concise and efficient syntheses of the aminocyclitol cores of hygromycin A (HMA) and methoxyhygromycin (MHM) have been achieved starting from readily available <i>myo</i>-inositol. Reductive cleavage of <i>myo</i>-inositol orthoformate to the corresponding 1,3-acetal, stereospecific introduction of the amino group via the azide, and resolution of a <i>racemic</i> cyclitol derivative as its diastereomeric mandelate esters are the key steps in the synthesis. Synthesis of the aminocyclitol core of hygromycin A involved chromatography in half of the total number of steps, and the aminocyclitol core of methoxyhygromycin involved only one chromatography

Synthesis of the Aminocyclitol Units of (−)-Hygromycin A and Methoxyhygromycin from <i>myo</i>-Inositol

Concise and efficient syntheses of the aminocyclitol cores of hygromycin A (HMA) and methoxyhygromycin (MHM) have been achieved starting from readily available <i>myo</i>-inositol. Reductive cleavage of <i>myo</i>-inositol orthoformate to the corresponding 1,3-acetal, stereospecific introduction of the amino group via the azide, and resolution of a <i>racemic</i> cyclitol derivative as its diastereomeric mandelate esters are the key steps in the synthesis. Synthesis of the aminocyclitol core of hygromycin A involved chromatography in half of the total number of steps, and the aminocyclitol core of methoxyhygromycin involved only one chromatography