Chirality Switching in Optical Resolution of Mandelic Acid in C1–C4 Alcohols: Elucidation of Solvent Effects Based on X‑ray Crystal Structures of Diastereomeric Salts

Chirality switching in the optical resolution of mandelic acid (MA) using (1<i>R</i>,2<i>S</i>)-2-amino-1,2-diphenylethanol (ADPE) in C1–C4 alcohols is demonstrated herein. Recrystallization of the diastereomeric mixture of the MA salts from <i>longer</i> alcohol solvents (<i>n</i>-PrOH, <i>s</i>-BuOH, <i>i</i>-BuOH, and <i>n</i>-BuOH) produced the (<i>R</i>)-MA salt, whereas the (<i>S</i>)-MA salt was preferentially deposited from <i>shorter</i> alcohol solvents (MeOH, EtOH, <i>i</i>-PrOH, and <i>t</i>-BuOH). Thermogravimetric analysis and ¹H NMR spectroscopy showed that all the solvents employed were incorporated in the diastereomeric salts and the stability of the incorporated alcohols increased with an increase in the effective surface area of their alkyl chains. The X-ray crystal structures of the eight solvated diastereomeric salt pairs revealed that the type of hydrogen-bonding network (sheetlike or columnar) and the arrangement of the columnar structures were controlled by the length of the included alcohol. By comparison of the two diastereomeric MA salt crystal structures, their relative stability to display chirality switching was investigated

Formation of Ternary Inclusion Crystal and Enantioseparation of Alkyl Aryl Sulfoxides by the Salt of Urea-Modified l‑Phenylalanine and an Achiral Amine

Chiral supramolecular hosts comprising urea-modified l-phenylalanines and achiral primary amines were developed, which facilitated enantioselective inclusion of alkyl aryl sulfoxides (<b>3</b>) up to 89% ee owing to the formation of ternary inclusion crystals. From the structural optimization of the components, the combination of <i>N</i>-(phenylcarbamoyl)-l-phenylalanine (<b>1a</b>) and benzhydrylamine (<b>2e</b>) showed the best inclusion ability among the considered supramolecular hosts. The type of the hydrogen-bonding network of ammonium-carboxylate salts <b>1a</b>·<b>2</b> was dependent on the steric bulk of combined primary amine <b>2</b>. The rigid phenylurea moiety of <b>1a</b> and moderate steric bulk of <b>2e</b> played an important role in their high inclusion ability. Host <b>1a</b>·<b>2e</b> afforded two ternary polymorphic inclusion crystals with the inclusion of acetonitrile. Furthermore, the crystal structures of <b>1a</b>·<b>2e</b>·<b>3</b> revealed that the inclusion of <b>3</b> was assisted by hydrogen bonding to the host and that stereoselectivity reversal occurred for larger sulfoxides, which was attributed to packing variations of one-dimensional hydrogen-bonding networks

Chirality Switching in Optical Resolution of Mandelic Acid in C1–C4 Alcohols: Elucidation of Solvent Effects Based on X‑ray Crystal Structures of Diastereomeric Salts

Chirality switching in the optical resolution of mandelic acid (MA) using (1<i>R</i>,2<i>S</i>)-2-amino-1,2-diphenylethanol (ADPE) in C1–C4 alcohols is demonstrated herein. Recrystallization of the diastereomeric mixture of the MA salts from <i>longer</i> alcohol solvents (<i>n</i>-PrOH, <i>s</i>-BuOH, <i>i</i>-BuOH, and <i>n</i>-BuOH) produced the (<i>R</i>)-MA salt, whereas the (<i>S</i>)-MA salt was preferentially deposited from <i>shorter</i> alcohol solvents (MeOH, EtOH, <i>i</i>-PrOH, and <i>t</i>-BuOH). Thermogravimetric analysis and ¹H NMR spectroscopy showed that all the solvents employed were incorporated in the diastereomeric salts and the stability of the incorporated alcohols increased with an increase in the effective surface area of their alkyl chains. The X-ray crystal structures of the eight solvated diastereomeric salt pairs revealed that the type of hydrogen-bonding network (sheetlike or columnar) and the arrangement of the columnar structures were controlled by the length of the included alcohol. By comparison of the two diastereomeric MA salt crystal structures, their relative stability to display chirality switching was investigated

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>