Photochemical formation of the elusive Dewar isomers of aromatic systems: why are substituted azaborines different?

Photochemical reactions enabling efficient transformation of aromatic systems into energetic but stable non-aromatic isomers have a long history in organic chemistry. One recently discovered reaction in this realm is that where derivatives of 1,2-azaborine, a compound isoelectronic with benzene in which two adjacent C atoms are replaced by B and N atoms, form the non-hexagon Dewar isomer. Here, we report quantum-chemical calculations that explain both why 1,2-azaborine is intrinsically more reactive toward Dewar formation than benzene, and how suitable substitutions at the B and N atoms are able to increase the corresponding quantum yield. We find that Dewar formation from 1,2-azaborine is favored by a pronounced driving force that benzene lacks, and that a large improvement in quantum yield arises when the reaction of substituted 1,2-azaborines proceeds without involvement of an intermediary ground-state species. Overall, we report new insights into making photochemical use of the Dewar isomers of aromatic compounds.

Correction to "Iterative Dual-Metal and Energy Transfer Catalysis Enables Stereodivergence in Alkyne Difunctionalization: Carboboration as Case Study".

[This corrects the article DOI: 10.1021/acscatal.3c03570.].

A Proof-of-Principle Design for Through-Space Transmission of Unidirectional Rotary Motion by Molecular Photogears.

The construction of molecular photogears that can achieve through-space transmission of the unidirectional double-bond rotary motion of light-driven molecular motors onto a remote single-bond axis is a formidable challenge in the field of artificial molecular machines. Here, we present a proof-of-principle design of such photogears that is based on the possibility of using stereogenic substituents to control both the relative stabilities of two helical forms of the photogear and the double-bond photoisomerization reaction that connects them. The potential of the design was verified by quantum-chemical modeling through which photogearing was found to be a favorable process compared to free-standing single-bond rotation ("slippage"). Overall, our study unveils a surprisingly simple approach to realizing unidirectional photogearing.

Iterative Dual-Metal and Energy Transfer Catalysis Enables Stereodivergence in Alkyne Difunctionalization: Carboboration as Case Study.

Stereochemically defined tetrasubstituted olefins are widespread structural elements of organic molecules and key intermediates in organic synthesis. However, flexible methods enabling stereodivergent access to E and Z isomers of fully substituted alkenes from a common precursor represent a significant challenge and are actively sought after in catalysis, especially those amenable to complex multifunctional molecules. Herein, we demonstrate that iterative dual-metal and energy transfer catalysis constitutes a unique platform for achieving stereodivergence in the difunctionalization of internal alkynes. The utility of this approach is showcased by the stereodivergent synthesis of both stereoisomers of tetrasubstituted ß-boryl acrylates from internal alkynoates with excellent stereocontrol via sequential carboboration and photoisomerization. The reluctance of electron-deficient internal alkynes to undergo catalytic carboboration has been overcome through cooperative Cu/Pd-catalysis, whereas an Ir complex was identified as a versatile sensitizer that is able to photoisomerize the resulting sterically crowded alkenes. Mechanistic studies by means of quantum-chemical calculations, quenching experiments, and transient absorption spectroscopy have been applied to unveil the mechanism of both steps.

HOMER: a reparameterization of the harmonic oscillator model of aromaticity (HOMA) for excited states.

Excited-state aromaticity (ESA) and antiaromaticity (ESAA) are by now well-established concepts for explaining photophysical properties and photochemical reactivities of cyclic, conjugated molecules. However, their application is less straightforward than the corresponding process by which the thermal chemistry of such systems is rationalized in terms of ground-state aromaticity (GSA) and antiaromaticity (GSAA). Recognizing that the harmonic oscillator model of aromaticity (HOMA) provides an easy way to measure aromaticity on geometric grounds, it is therefore notable that this model is yet to be parameterized for excited states. Against this background, we here present a new parameterization of HOMA - termed HOMER - for the T1 state of both carbocyclic and heterocyclic compounds based on high-level quantum-chemical calculations. Considering CC, CN, NN and CO bonds and testing the parametrization using calculated magnetic data as reference, we find that the description of ESA and ESAA by HOMER is superior to that afforded by the original HOMA scheme, and that it reaches the same overall quality as HOMA does for GSA and GSAA. Furthermore, we demonstrate that the derived HOMER parameters can be used for predictive modeling of ESA and ESAA at very different levels of theory. Altogether, the results highlight the potential of HOMER to facilitate future studies of ESA and ESAA.

Unveiling Photodegradation and Photosensitization Mechanisms of Unconjugated Pterins.

Invited for the cover of this issue are Enrique M. Arpa (Linköping University) and Inés Corral (Universidad Autónoma de Madrid). The image depicts two examples where pterin chemistry is relevant, the wing coloration of some butterflies and the cytotoxic action in vitiligo. Read the full text of the article at 10.1002/chem.202300519.

Unveiling Photodegradation and Photosensitization Mechanisms of Unconjugated Pterins.

Unconjugated pterins are ubiquitous molecules that participate in countless enzymatic processes and are potentially involved in the photosensitization of singlet oxygen, amino acids, and nucleotides. Following electronic excitation with UV-A light, some of these pterins degrade, producing hydrogen peroxide as the main side product. This process, which is known to take place in vivo, contributes to oxidative stress and melanocyte destruction in vitiligo. In this work, we present for the first time mechanistic insight into the formation of transient triplet species that simultaneously trigger Type I and Type II photosensitizing processes and the initiation of degradation processes. Our calculations reveal that photodegradation of 6-biopterin, which accumulates in the skin of vitiligo patients, leads to 6-formylpterin through a retro-aldol reaction, and subsequently to 6-carboxypterin through a water-mediated aldehyde oxidation. Additionally, we show that the changes in the photosensitizing potential of these systems with pH come from the modulation of their excited-state redox potentials.

2-Oxopurine Riboside: A Dual Fluorescent Analog and Photosensitizer for RNA/DNA Research.

There is significant interest in developing suitable nucleoside analogs exhibiting high fluorescence and triplet yields to investigate the structure, dynamics, and binding properties of nucleic acids and promote selective photosensitized damage to DNA/RNA, respectively. In this study, steady-state, laser flash photolysis, time-resolved IR luminescence, and femtosecond broad-band transient absorption spectroscopies are combined with quantum chemical calculations to elucidate the excited-state dynamics of 2-oxopurine riboside in aqueous solution and to investigate its prospective use as a fluorescent or photosensitizer analog. The Franck-Condon population in the S1 (ππ*) state decays through a combination of solvent and conformational relaxation to its minimum in 1.9 ps. The population trapped in the 1ππ* minimum bifurcates to either fluoresce or intersystem cross to the triplet manifold within ca. 5 ns, while another fraction of the population decays nonradiatively to the ground state. It is demonstrated that 2-oxopurine riboside exhibits both high fluorescent (48%) and significant triplet (between 10% and 52%) yields, leading to a yield of singlet oxygen generation of 10%, making this nucleoside analog a dual fluorescent and photosensitizer analog for DNA and RNA research.

Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes.

The cooperative action of the acetate ligand, the 2-pyridyl sulfonyl (SO2Py) directing group on the alkyne substrate, and the palladium catalyst has been shown to be crucial for controlling reactivity, regioselectivity, and stereoselectivity in the acetoxylation of unsymmetrical internal alkynes under mild reaction conditions. The corresponding alkenyl acetates were obtained in good yields with complete levels of ß-regioselectivity and anti-acetoxypalladation stereocontrol. Experimental and computational analyses provide insight into the reasons behind this delicate interplay between the ligand, directing group, and the metal in the reaction mechanism. In fact, these studies unveil the multiple important roles of the acetate ligand in the coordination sphere at the Pd center: (i) it brings the acetic acid reagent into close proximity to the metal to allow the simultaneous activation of the alkyne and the acetic acid, (ii) it serves as an inner-sphere base while enhancing the nucleophilicity of the acid, and (iii) it acts as an intramolecular acid to facilitate protodemetalation and regeneration of the catalyst. Further insight into the origin of the observed regiocontrol is provided by the mapping of potential energy profiles and distortion-interaction analysis.

Transient changes in aromaticity and their effect on excited-state proton transfer reactions.

The common approach to investigate the impact of aromaticity on excited-state proton transfer by probing the (anti)aromatic character of reactants and products alone is scrutinized by modelling such reactions involving 2-pyridone. Thereby, it is found that energy barriers can be strongly influenced by transient changes in aromaticity unaccounted for by this approach, particularly when the photoexcited state interacts with a second excited state. Overall, the modelling identifies a pronounced effect overlooked by most studies on this topic.

A molecular insight into the photophysics of barbituric acid, a candidate for canonical nucleobases' ancestor.

This work investigates the photophysics of barbituric acid at different pH conditions using ab initio methods. Our calculations ascribe the most intense bands at ca. 260 nm at neutral pH and 210 nm at acidic pH conditions in the absorption spectra of this chromophore to the lowest lying ππ* transitions. Consistently with the ultrashort excited state lifetimes experimentally registered, the potential energy landscapes of both the neutral and deprotonated forms of barbituric acid combined with the interpretation of their transient absorption spectra suggest the deactivation of these systems along the singlet manifold. Compared to uracil, its closest natural nucleobase, barbituric acid presents a red shifted absorption spectrum, due to the lowering by more than 0.5 eV of the lowest-energy ππ* excited state, and a much more complex topography of the S1 potential energy surface, with several energetically accessible local minima. This fact, however, does not affect the excited state lifetimes, which for barbituric acid were experimentally registered in the sub-ps time scale.

On the Origin of the Photostability of DNA and RNA Monomers: Excited State Relaxation Mechanism of the Pyrimidine Chromophore.

Today's genetic composition is the result of continual refinement processes on primordial heterocycles present in prebiotic Earth and at least partially regulated by ultraviolet radiation. Femtosecond transient absorption spectroscopy and state-of-the-art ab initio calculations are combined to unravel the electronic relaxation mechanism of pyrimidine, the common chromophore of the nucleobases. The excitation of pyrimidine at 268 nm populates the S1(nπ*) state directly. A fraction of the population intersystem crosses to the triplet manifold within 7.8 ps, partially decaying within 1.5 ns, while another fraction recovers the ground state in >3 ns. The pyrimidine chromophore is not responsible for the photostability of the nucleobases. Instead, C2 and C4 amino and/or carbonyl functionalization is essential for shaping the topography of pyrimidine's potential energy surfaces and results in accessible conical intersections between the initially populated electronic excited state and the ground state.

Intramolecular Hydrogen Bond Activation: Thiourea-Organocatalyzed Enantioselective 1,3-Dipolar Cycloaddition of Salicylaldehyde-Derived Azomethine Ylides with Nitroalkenes.

An organocatalytic strategy for the synthesis of tetrasubstituted pyrrolidines with monoactivated azomethine ylides in high enantiomeric excess and excellent exo/endo selectivity is presented. The key to success is the intramolecular activation via hydrogen bonding through an o-hydroxy group, which allows the dipolar cycloaddition to take place in the presence of azomethine ylides bearing only one activating group. The intramolecular hydrogen bond in the azomethine ylide and the intermolecular hydrogen bond with the catalyst have been demonstrated by DFT calculations and mechanistic proofs to be crucial for the reaction to proceed.

Catalytic Asymmetric Synthesis of Bicycloprolines by a 1,3-Dipolar Cycloaddition/Intramolecular Alkylation Strategy.

The diastereoselective one-pot synthesis of hexahydrocyclopenta[b]pyrrole derivatives (bicycloprolines) has been achieved by base-mediated reactions of (E)-tert-butyl 6-bromo-2-hexenoate with α-imino esters. The catalytic asymmetric version of this process has been efficiently achieved using the Cu(I)/(R)-DTBM-Segphos complex as a catalyst following a two-step 1,3-dipolar cycloaddition/intramolecular alkylation sequence.