Norcaradiene-Cycloheptatriene Equilibrium: A Heavy-Atom Quantum Tunneling Case.

The equilibrium between norcaradiene and cycloheptatriene, which has captivated chemists for more than half a century, is revisited by state-of-the-art quantum chemical calculations. Our theoretical data significantly deviate from the experimental results (J. Am. Chem. Soc., 1981, 26, 7791-7792), especially at low temperatures, where isomerization is dominated by heavy-atom tunneling. This effect results in an extremely short half-life for norcaradiene, rendering it undetectable. This work sheds light on this equilibrium, updating the kinetic and thermodynamic data while also expanding the repertoire of organic reactions controlled by this exotic quantum effect.

A fully diastereoselective oxidation of a mesoionic dipole with triplet molecular oxygen.

Oxidations with molecular oxygen are ubiquitous processes in biological systems where cofactor-dependent enzymes activate either oxygen or hydrogen peroxide to induce multichannel pathways. In stark contrast, such slow atmospheric oxidations are seldom harnessed in chemical synthesis and analysis. The present study unveils an unusual aerobic oxidation of a mesoionic dipole leading easily to a more functionalized skeleton. Although the synthetic scope has not been explored, two key considerations emerge from this transformation, as it proceeds with complete diastereoselection and could be successfully extrapolated to structurally related mesoionic chirons without racemization. How this oxidation actually occurs proved to be puzzling from the onset and only high-level computation reveals a cascade transformation, whose results reconcile theory and experiment. Hopefully, the mechanistic insights should help us to understand better the autoxidative reactions of organic molecules.

From prebiotic chemistry to supramolecular oligomers: urea-glyoxal reactions.

A fundamental question in origin-of-life studies and astrochemistry concerns the actual processes that initiate the formation of reactive monomers and their oligomerization. Answers lie partly in the accurate description of reaction mechanisms compatible with environments plausible on early Earth as well as cosmological scenarios in planetary factories. Here we show in detail that reactions of urea-as archetypal prebiotic substance-and reactive carbonyls-exemplified by glyoxal-lead to a vast repertoire of oligomers, in which different five- and six-membered non-aromatic heterocycles self-assemble and insert into chains or dendritic-like structures with masses up to 1000 Da. Such regular patterns have been interpreted by experimental and computational methods. A salient conclusion is that such processes most likely occur through SN-type mechanisms on hydrated or protonated species. Remarkably, such supramolecular oligomeric mixtures can be easily isolated from organic solvents, thus opening the door to the generation of novel urea-containing polymers with potential applications in materials chemistry and beyond.

Formation of S-alkyl thiophenium ionic liquids: mechanistic rationale and structural relationships.

The quaternization of thiophenes through S-alkylation reactions with iodoalkanes in the presence of silver salts opens the door to a new family of room-temperature ionic liquids, yet relatively unexplored in terms of chemical reactivity and applications. This computational study provides a mechanistic rationale that accounts for their formation. The results are consistent with the calculated energy barriers of the corresponding transition structures. Calculations indicate that the geometry at the sulfur atom goes from flat to tetrahedral during salt formation, and the electron delocalization of thiophene is greatly reduced, if not lost, as inferred from aromaticity indexes. Moreover, the rationale explains the influence of polarizable anions on S-alkylation and why alkyl substitution at the α-position of thiophenes gives rise to more stable species than unsubstituted derivatives.

Formation of Cyanamide-Glyoxal Oligomers in Aqueous Environments Relevant to Primeval and Astrochemical Scenarios: A Spectroscopic and Theoretical Study.

The condensation of cyanamide and glyoxal, two well-known prebiotic monomers, in an aqueous phase has been investigated in great detail, demonstrating the formation of oligomeric species of varied structure, though consistent with generalizable patterns. This chemistry involving structurally simple substances also illustrates the possibility of building molecular complexity under prebiotically plausible conditions, not only on Earth, but also in extraterrestrial scenarios. We show that cyanamide-glyoxal reactions in water lead to mixtures comprising both acyclic and cyclic fragments, largely based on fused five- and six-membered rings, which can be predicted by computation. Remarkably, such a mixture could be identified using high-resolution electrospray ionization (ESI) mass spectrometry and spectroscopic methods. A few mechanistic pathways can be postulated, most involving the intermediacy of glyoxal cyanoimine and further chain growth, thus increasing the diversity of the observed products. This rationale is supported by theoretical analyses with clear-cut identification of all of the stationary points and transition-state structures. The properties and structural differences of oligomers obtained under thermodynamic conditions in water as opposed to those isolated by precipitation from organic media are also discussed.

Mechanistic studies of 1,3-dipolar cycloadditions of bicyclic thioisomünchnones with alkenes. A computational rationale focused on donor-acceptor interactions.

This paper describes a mechanistic study, with the interplay of experiment and theory, on the cycloadditions of a bicyclic mesoionic 1,3-dipole versus a series of representative symmetrical (1-phenyl-1H-pyrrole-2,5-dione and dimethyl maleate) and asymmetrical [(E)-(2-nitrovinyl)benzene, acrylonitrile, and but-3-en-2-one] olefinic dipolarophiles. These results allow a comparative analysis with monocyclic dipoles and open further avenues to structurally diversified heteroatom-rich rings. The unichiral version of the bicyclic dipole leads to adducts containing up to five chiral centers, whose formation proceeds with high levels of facial stereoinduction in reactions involving bulky dipolarophiles. The second and largest part of this study provides a theoretical interrogation on the pericyclic mechanism with DFT-methods [M06-2X/6-311++G(d,p)]. In order to get further mechanistic insights, we have also explored charge transfers between reaction partners using NBO analysis, which satisfactorily justifies the stereochemical outcome.

Revisiting Homochiral versus Heterochiral Interactions through a Long Detective Story of a Useful Azobis-Nitrile and Puzzling Racemate.

This paper documents and reinvestigates the solid-state and crystal structures of 4,4'-azobis-4-cyanopentanoic acid (ACPA), a water-soluble azobis-nitrile of immense utility as a radical initiator in living polymerizations and a labile mechanophore that can be embedded within long polymer chains to undergo selective scission under mechanical activation. Surprisingly, for such applications, both the commercially available reagent and their derivatives are used as "single initiators" when this azonitrile is actually a mixture of stereoisomers. Although the racemate and meso compounds were identified more than half a century ago and their enantiomers were separated by classical resolution, there have been confusing narratives dealing with their characterization, the existence of a conglomeratic phase, and fractional crystallization. Our results report on the X-ray crystal structures of all stereoisomers for the first time, along with further details on enantiodiscrimination and the always intriguing arguments accounting for the stability of homochiral versus heterochiral crystal aggregates. To this end, metadynamic (MTD) simulations on stereoisomer molecular aggregates were performed to capture the incipient nucleation events at the picosecond time scale. This analysis sheds light on the driving homochiral aggregation of ACPA enantiomers.