Supramolecular Mille-Feuille: Adaptive Guest Inclusion in a New Aliphatic Guanidinium Monosulfonate Hydrogen-Bonded Framework.

During the past three decades, the ability of guanidinium arenesulfonate host frameworks to encapsulate a wide range of guests has been amply demonstrated, with more than 700 inclusion compounds realized. Herein, we report crystalline inclusion compounds based on a new aliphatic host, guanidinium cyclohexanemonosulfonate, which surprisingly exhibits four heretofore unobserved architectures, as described by the projection topologies of the organosulfonate residues above and below hydrogen-bonded guanidinium sulfonate sheets. The inclusion compounds adopt a layer motif of guanidinium sulfonate sheets interleaved with guest molecules, resembling a mille-feuille pastry. The aliphatic character of this remarkably simple host, combined with access to greater architectural diversity and adaptability, enables the host framework to accommodate a wide range of guests and promises to expand the utility of guanidinium organosulfonate hosts.

Halogen Atom Participation in Guiding the Stereochemical Outcomes of Acetal Substitution Reactions.

Acetal substitution reactions of α-halogenated five- and six-membered rings can be highly stereoselective. Erosion of stereoselectivity occurs as nucleophilicity increases, which is consistent with additions to a halogen-stabilized oxocarbenium ion, not a three-membered-ring halonium ion. Computational investigations confirmed that the open-form oxocarbenium ions are the reactive intermediates involved. Kinetic studies suggest that hyperconjugative effects and through-space electrostatic interactions can both contribute to the stabilization of halogen-substituted oxocarbenium ions.

Hyperconjugative Interactions of the Carbon-Halogen Bond that Influence the Geometry of Cyclic α-Haloacetals.

The analysis of the structures of low-energy conformers of different α-haloacetals reveals changes in bond lengths and geometries that correspond to stabilizing orbital interactions that contribute to the ground-state structures of these systems. Several factors, including the electron-donating and electron-accepting abilities of the substituents on the ring, affect the degree of the electronic interactions in these carbohydrate-like systems. The presence of an α-halogen atom that can participate in hyperconjugation has been shown to contribute to the structural characteristics of the low-energy conformer. The experimental evidence is supported by natural bond order (NBO) analysis to identify the types of interactions and to assess their relative importance.

Conformationally Biased Ketones React Diastereoselectively with Allylmagnesium Halides.

The addition of the highly reactive reagent allylmagnesium halide to α-substituted acyclic chiral ketones proceeded with high stereoselectivity. The stereoselectivity cannot be analyzed by conventional stereochemical models because these reactions do not conform to the requirements of those models. Instead, the stereoselectivity arises from the approach of the nucleophile to the most accessible diastereofaces of the lowest-energy conformations of the ketones. High stereoselectivity is expected, and the stereochemical outcome can be predicted, with conformationally biased ketones that have sterically distinguishable diastereofaces wherein only one face is accessible for nucleophilic addition. The conformations of the ketones can be determined by a combination of computational modeling and, in some cases, structure determination by X-ray crystallography.

Diastereoselective Additions of Allylmagnesium Reagents to α-Substituted Ketones When Stereochemical Models Cannot Be Used.

The stereoselectivities of reactions of allylmagnesium reagents with chiral ketones cannot be easily explained by stereochemical models. Competition experiments indicate that the complexation step is not reversible, so nucleophiles cannot access the widest range of possible encounter complexes and therefore cannot be analyzed easily using available models. Nevertheless, additions of allylmagnesium reagents to a ketone can still be stereoselective provided that the carbonyl group adopts a conformation that leads to one face being completely blocked from the approach of the allylmagnesium reagent.