Formation, Selective Encapsulation, and Tautomerization Control of Isoindolone Utilizing Guanidinium Sulfonate Frameworks.

Herein we report the use of tetrakis (guanidinium) pyrenetetrasulfonate (G4PYR) and bis (guanidinium) 1,5-napthalene disulfonate (G2NDS) to catalyze the cyclization of 2-cyanobenzamide (1) to isoindolone (2). Moreover, we demonstrate the remarkable selectivity of these guanidinium organosulfonate hosts in encapsulating 2 over 1. By thoroughly investigating the intramolecular cyclization reaction, we determined that guanidinium and the organosulfonate moiety acts as the catalyst in this process. Additionally, 2 is selectively encapsulated, even in mixtures of other structurally similar heterocycles like indole. Furthermore, the tautomeric state of 2 (amino isoindolone (2-A) and imino isoindolinone forms (2-I)) can be controlled by utilizing different guanidinium organosulfonate frameworks.

Structure Elucidation of Pharmaceutically Relevant Compounds within Pyrene-based Frameworks.

Single crystal X-ray diffraction (SCXRD) is the preferred and most accurate technique for determining molecular structures. However, it can present challenges when dealing with specific small molecules and active pharmaceutical ingredients (APIs), as many do not form quality crystals without coformers or can be unstable. In this study, we introduce tetrakis(guanidinium) pyrenetetrasulfonate (G4PYR), a robust guanidinium-organosulfonate (GS) framework that efficiently encapsulates small molecules and APIs rich in functional groups. The hydrogen bonding frameworks formed by G4PYR display well-ordered structures with predictable pyrene-pyrene distances, making them ideally suited for targeting arene-based APIs with pendant groups. Successful encapsulation of various guests, including benzaldehyde, benzamide, and arenes containing multiple hydrogen bond donors and acceptors like uracil and thymine, was achieved. Furthermore, we successfully encapsulated important pharmaceutical and biologically relevant compounds, such as lidocaine, ropinirole, adenosine, thymidine, and others. Notably, we present a workflow for investigating host-guest complex formation using powder X-ray diffraction and high throughput experimentation.

Benchmarking Guanidinium Organosulfonate Hydrogen-Bonded Frameworks for Structure Determination of Encapsulated Guests.

Single crystal X-ray diffraction (SCXRD) is arguably the most definitive method for molecular structure determination, but it is often challenged by compounds that are liquids or oils at room temperature or do not form crystals adequate for analysis. Our laboratory previously reported a simple, cost-effective, single-step crystallization method based on guanidinium organosulfonate (GS) hydrogen bonded frameworks for structure determination of a wide range of encapsulated guest molecules, including assignment of the absolute configuration of chiral centers. Herein, we expand on those results and report a head-to-head comparison of the GS method with adamantoid "molecular chaperones", which have been reported to be useful hosts for structure determination. Inclusion compounds limited to only two GS hosts are characterized by low R1 values and Flack parameters, infrequent disorder of the host and guest, and manageable disorder when it does exist. The structures of some target molecules that were not included or resolved using the adamantoid chaperones were successfully included and resolved by the GS hosts, and vice versa. Of the 32 guests attempted by the GS method, 31 inclusion compounds afforded successful guest structure solutions, a 97% success rate. The GS hosts and adamantoid chaperones are complementary with respect to guest inclusion, arguing that both should be employed in the arsenal of methods for structure determination. Furthermore, the low cost of organosulfonate host components promises an accessible route to molecular structure determination for a wide range of users.

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.

Electrosynthesis of iminophosphoranes and applications in nickel catalysis.

P(v) iminophosphorane compounds are accessed via electrochemical oxidation of commercially available P(iii) phosphines, including mono-, di- and tri-dentate phosphines, as well as chiral phosphines. The reaction uses inexpensive bis(trimethylsilyl)carbodiimide as an efficient and safe aminating reagent. DFT calculations, cyclic voltammetry, and NMR studies provide insight into the reaction mechanism. The proposed mechanism reveals a special case of sequential paired electrolysis. DFT calculations of the frontier orbitals of an iminophosphorane are compared with those of the analogous phosphines and phosphine oxides. X-ray crystallographic studies of the ligands as well as a Ni-coordination complex provide structural insight for these ligands. The utility of these iminophosphoranes as ligands is demonstrated in nickel-catalyzed cross-electrophile couplings including C(sp2)-C(sp3) and C(sp2)-C(sp2) couplings, an electrochemically driven C-N cross-coupling, and a photochemical arylative C(sp3)-H functionalization. In some cases, these new ligands provide improved performance over commonly used sp2-N-based ligands (e.g. 4,4'-di-tert-butyl-2,2'-bipyridine).