Photoremovable Protecting Groups: Across the Light Spectrum to Near-Infrared Absorbing Photocages

We discuss the past decade of progress in the field of photoremovable protecting groups that allowed the development of photocages activatable by near-IR light and highlight the individual conceptual advancements that lead to general guidelines to design new such photoremovable protecting groups. We emphasize the importance of understanding the individual photochemical reaction mechanisms that was necessary to achieve this progress and provide an outlook of the subsequent steps to facilitate a swift translation of this research into clinical praxis. Since this issue of CHIMIA is dedicated to the late Prof. Thomas Bally, we decided to provide a personal perspective on the field to which he contributed himself. We tried to write this review with the general readership of CHIMIA in mind in a hope to pay a tribute to the extraordinary dedication and clarity with which Thomas Bally used to explain abstract chemical concepts to his students or colleagues. We are uncertain whether we matched such challenge but we believe that he would have liked such approach very much

The Primary steps in excited-state hydrogen transfer: the phototautomerization of o-nitrobenzyl derivatives

The quantum yield for the release of leaving groups from o-nitrobenzyl “caged” compounds varies greatly with the nature of these leaving groups, for reasons that have never been well understood. We found that the barriers for the primary hydrogen-atom transfer step and the efficient nonradiative processes on the excited singlet and triplet surfaces determine the quantum yields. The excited-state barriers decrease when the exothermicity of the photoreaction increases, in accord with Bell–Evans–Polanyi principle, a tool that has never been applied to a nonadiabatic photoreaction. We further introduce a simple ground-state predictor, the radical-stabilization energy, which correlates with the computed excited-state barriers and reaction energies, and that might be used to design new and more efficient photochemical processes

Trimesityltriangulene: a persistent derivative of Clar's hydrocarbon

Triangulene, known as Clar’s hydrocarbon, is a prototypical non-Kekule ́ diradical comprised of six benzenoid rings fused in a trian-gular shape. We synthesized and characterized its trimesityl derivative, illustrating that three bulky substituents installed in the centers of the zigzag edges suffice to protect all reactive positions. This work brings prospects to use triangulene and its open-shell analogs in spintronic materials via solution-phase synthesis

Gram-Scale Synthesis and Supramolecular Complex of Precursors of Clar’s Hydrocarbon Triangulene

We present to date the most efficient gramscale synthesis of triangulene-4,8-dione and 12-hydroxytriangulene- 4,8-dione, the precursors of Clar’s hydrocarbon, in overall yields >50%. The direct dihydroprecursors of triangulene, obtained upon reduction of triangulene-4,8- dione, were stabilized in a supramolecular complex with a tetracationic cyclophane ExBox4+ and characterized by singlecrystal X-ray crystallography. This result represents the first step in an endeavor to stabilize the fragile core of triangulene in an inclusion complex in solution and solid state

Cethrene: The Chameleon of Woodward–Hoffmann Rules

We demonstrate that the electrocyclic (EC) ring-closure of cethrene in solution proceeds in a conrotatory mode both thermally and photochemically. The facile photochemical EC process promises that cethrene can serve as an efficient chiroptical switch operated solely by light. As for the thermally activated EC reaction, a low reaction barrier and a solvation effect on the EC rate indicate that the C2-symmetric pathway predicted by DFT calculations might not be the correct mechanism. Instead, we argue that the molecular symmetry decreases along the reaction coordinate as a consequence of the low-energy singlet excited state in this diradicaloid molecule, which might lead to a lower activation energy in accord with that determined through kinetic studies. Cethrene, therefore, represents a thought-provoking molecular chameleon of the Woodward–Hoffmann rules that puts our chemical concepts and intuition to test

A Photo-Favorskii Ring Contraction Reaction: The Effect of Ring

The effect of ring size on the photo-Favorskii induced ring-contraction reaction of the hydroxybenzocycloalkanonyl acetate and mesylate esters (7a–d, 8a–c) has provided new insight into the mechanism of the rearrangement. By monotonically decreasing the ring size in these cyclic derivatives, the increasing ring strain imposed on the formation of the elusive bicyclic spirocyclopropanone 20 results in a divergence away from rearrangement and toward solvolysis. Cycloalkanones of seven or eight carbons undergo a highly efficient photo-Favorskii rearrangement with ring contraction paralleling the photochemistry of p-hydroxyphenacyl esters. In contrast, the five-carbon ring does not rearrange but is diverted to the photosolvolysis channel avoiding the increased strain energy that would accompany the formation of the spirobicyclic ketone, the “Favorskii intermediate 20”. The six-carbon analogue demonstrates the bifurcation in reaction channels, yielding a solvent-sensitive mixture of both. Employing a combination of time-resolved absorption measurements, quantum yield determinations, isotopic labeling, and solvent variation studies coupled with theoretical treatment, a more comprehensive mechanistic description of the rearrangement has emerged

Dimethylcethrene: A Chiroptical Diradicaloid Photoswitch

We describe the synthesis and properties of 13,14-dimethylcethrene, a prototype of a chiral diradicaloid photochemical switch that can be transformed reversibly via conrotatory electrocyclization to its more stable closed form by light (630 nm) or heat and back to its open form by light (365 nm). This system illustrates how the chemical reactivity of a diradicaloid molecule can be translated into a switching function, which alters substantially all electronic parameters, namely, the HOMO–LUMO and the singlet–triplet (ST) energy gaps, and the degree of helical twist. As a result, distinct changes in the optical and chiroptical properties of this system were observed, which allowed us to monitor the switching process by a variety of spectroscopic techniques, including NMR, UV–vis, and CD. In comparison to the previously reported parent molecule cethrene, this system benefits from two methyl substituents installed in the fjord region, which account for the stability of the closed form against oxidation and racemization. The methyl substituents increase the ST energy gap of 13,14-dimethylcethrene by ∼4 kcal mol–1 in comparison to cethrene. Our DFT calculations reveal that the larger ST gap is a result of electronic and geometric effects of the methyl substituents and show the potential of related systems to act as magnetic switches at room temperature

Supramolecular photochemistry of encapsulated caged ortho-nitrobenzyl triggers

ortho-Nitrobenzyl (oNB) triggers have been extensively used to release various molecules of interest. However, the toxicity and reactivity of the spent chromophore, o-nitrosobenzaldehyde, remains an unaddressed difficulty. In this study we have applied the well-established supramolecular photochemical concepts to retain the spent trigger o-nitrosobenzaldehyde within the organic capsule after release of water-soluble acids and alcohols. The sequestering power of organic capsules for spent chromophores during photorelease from ortho-nitrobenzyl esters, ethers and alcohols is demonstrated with several examples.National Science FoundationNational Science Foundation (NSF) [CHE-1807729]Kansas University Endowment AssociationFCT - Foundation for Science and TechnologyPortuguese Foundation for Science and Technology [UID/Multi/04326/2019, EMBRC.PT ALG-01-0145-FEDER-022121