Publications

2024

Xu, Yi; Peschel, Martin; Jänchen, Miriam; Foja, Richard; Storch, Golo; Thyrhaug, Erling; de Vivie-Riedle, Regina; Hauer, Jürgen: Determining Excited-State Absorption Properties of a Quinoid Flavin by Polarization-Resolved Transient Spectroscopy, J. Phys. Chem A. 128, 2024, 3830-3839.

 

 

As important naturally occurring chromophores, photophysical/chemical properties of quinoid flavins have been extensively studied both experimentally and theoretically. However, little is known about the transition dipole moment (TDM) orientation of excited-state absorption transitions of these important compounds. This aspect is of high interest in the fields of photocatalysis and quantum control studies. In this work, we employ polarization-associated spectra (PAS) to study the excited-state absorption transitions and the underlying TDM directions of a standard quinoid flavin compound. As compared to transient absorption anisotropy (TAA), an analysis based on PAS not only avoids diverging signals but also retrieves the relative angle for ESA transitions with respect to known TDM directions. Quantum chemical calculations of excited-state properties lead to good agreement with TA signals measured in magic angle configuration. Only when comparing experiment and theory for TAA spectra and PAS, do we find deviations when and only when the S0 → S1 of flavin is used as a reference. We attribute this to the vibronic coupling of this transition to a dark state. This effect is only observed in the employed polarization-controlled spectroscopy and would have gone unnoticed in conventional TA.

 

Märsch, Julia; Reiter, Sebastian; Rittner, Thomas; Rodriguez-Lugo, Rafael E.; Whitfield, Maximilian; Scott, Daniel J.; Jan Kutta, Roger; Nuernberger, Patrick; de Vivie-Riedle, Regina; Wolf, Robert: Cobalt-Mediated Photochemical C−H Arylation of Pyrroles, Angew. Chem. Int. Ed. 2024, e202405780

 

 

Precious metal complexes remain ubiquitous in photoredox
catalysis (PRC) despite concerted efforts to find more earth-abundant
catalysts and replacements based on 3d metals in particular. Most
otherwise plausible 3d metal complexes are assumed to be unsuitable
due to short-lived excited states, which has led researchers to
prioritize the pursuit of longer excited-state lifetimes through careful
molecular design. However, we report herein that the C−H arylation
of pyrroles and related substrates (which are benchmark reactions for
assessing the efficacy of photoredox catalysts) can be achieved using
a simple and readily accessible octahedral bis(diiminopyridine) cobalt
complex, [1-Co](PF6)2. Notably, [1-Co]2+ efficiently functionalizes
both chloro- and bromoarene substrates despite the short excitedstate
lifetime of the key photoexcited intermediate *[1-Co]2+ (8 ps).
We present herein the scope of this C−H arylation protocol and
provide mechanistic insights derived from detailed spectroscopic and
computational studies. These indicate that, despite its transient
existence, reduction of *[1-Co]2+ is facilitated via pre-assembly with
the NEt3 reductant, highlighting an alternative strategy for the future
development of 3d metal-catalyzed PRC.

 

Bergwinkl, Sebastian; Nuernberger, Patrick; Dick, Bernhard; Kutta, Roger Jan: Enhanced intersystem crossing in a thiohelicene, ChemPhotoChem 8, 2024, e202300343.

The photophysics of a helicene derivative in which two benzene units are replaced by thiophene units (thiohelicene, 6H) was studied by steady state and transient absorption and emission spectroscopies covering time ranges from femtoseconds to minutes. Efficient intersystem crossing (ISC) to the triplet state was observed, by far exceeding that of the parent helicene and the corresponding oxo-helicene. Quantum chemical calculations indicate that the helical distortion and the heavy atom effect of sulfur cooperate in promoting spin-orbit coupling, and that the most efficient decay channel involved the T2 or even the T3 state. These insights can help in the design of more efficient triplet sensitizes for may applications.

Hierlmeier, Gabriele; Kutta, Roger Jan; Coburger, Peter; Stammler, Hans-Georg; Schwabedissen, Jan; Mitzel, Norbert W.; Dimitrova, Maria; Berger, Raphael J.F.; Nuernberger, Patrick; Wolf, Robert: Structure and photochemistry of di-tert-butyldiphosphatetrahedrane, Chem. Sci. 15, 2024, 5596-5603.

Di-tert-butyldiphosphatetrahedrane (tBuCP)2 (1) is a mixed carbon- and phosphorus-based tetrahedral molecule, isolobal to white phosphorus (P4). However, despite the fundamental significance and well-explored reactivity of the latter molecule, the precise structure of the free (tBuCP)2 molecule (1) and a detailed analysis of its electronic properties have remained elusive. Here, single-crystal X-ray structure determination of 1 at low temperature confirms the tetrahedral structure. Furthermore, quantum chemical calculations confirm that 1 is isolobal to P4 and shows a strong largely isotropic diamagnetic response in the magnetic field and thus pronounced spherical aromaticity. A spectroscopic and computational study on the photochemical reactivity reveals that diphosphatetrahedrane 1 readily dimerises to the ladderane-type phosphaalkyne tetramer (tBuCP)4 (2) under irradiation with UV light. With sufficient thermal activation energy, the dimerisation proceeds also in the dark. In both cases, an isomerisation to a 1,2-diphosphacyclobutadiene 1′ is the first step. This intermediate subsequently undergoes a [2 + 2] cycloaddition with a second 1,2-diphosphacyclobutadiene molecule to form 2. The 1,2-diphosphacyclobutadiene intermediate 1′ can be trapped chemically by N-methylmaleimide as an alternative  [2 + 2] cycloaddition partner.

Grotjahn, Sascha; Graf, Christina; Zelenka, Jan; Pattanaik, Aryaman; Müller, Lea; Jan Kutta, Roger; Rehbein, Julia, Roithová, Jana, Gschwind Ruth M.; Nuernberger, Patrick; König, Burkhard: Reactivity of superbasic carbanions generated via reductive radical-polar crossover in the context of photoredox catalysis, Angew. Chem. Int. Ed. 63, 2024, e202400815.

 

 

Photocatalytic reactions with a reductive radical-polar crossover (RRPCO) involve intermediates with carbanionic reactivity. These are best described as free carbanions. Reactions with such carbanions depend on the balance between their nucleophilicity and basicity. Deprotonation of reaction partners and common organic solvents such as acetonitrile, dimethylformamide, and dimethylsulfoxide is the main competing reaction to nucleophilic addition.

Yan, Peng; Stegbauer, Simone; Wu, Qinqin; Kolodzeiski, Elena; Stein, Christopher; Lu, Ping; Bach, Thorsten: Enantioselective Intramolecular ortho Photocycloaddition Reactions of 2-Acetonaphthones, Angew. Chem. Int. Ed. 2024, e202318126

 

 

2-Acetonaphthones, which bear an alkenyl group tethered to its C1 carbon atom via an oxygen atom, were found to undergo an enantioselective, intramolecular ortho photocycloaddition reaction. A chiral oxazaborolidine Lewis acid leads to a bathochromic absorption shift of the substrate and enables an efficient enantioface differentiation. Visible light irradiation (λ = 450 nm) triggers the reaction which is tolerant of various groups at almost any position except carbon atom C8 (16 examples, 53-99% yield, 80-97% ee). Consecutive reactions were explored including a sensitized rearrangement to tetrahydrobiphenylenes, which occurred with full retention of configuration. Evidence was collected that the catalytic photocycloaddition occurs via triplet intermediates, and the binding mode of the acetonaphthone to the chiral Lewis acid was elucidated by DFT calculations.

 

2023

Publications

Lemke, Yannick; Ochsenfeld, Christian: Highly accurate σ- and τ-functionals for beyond-RPA methods with approximate exchange kernels, J. Chem. Phys. 159, 2023, 194104

σ-Functionals are promising new developments for the Kohn–Sham correlation energy based upon the direct Random Phase Approximation (dRPA) within the adiabatic connection formalism, providing impressive improvements over dRPA for a broad range of benchmarks. However, σ-functionals exhibit a high amount of self-interaction inherited from the approximations made within dRPA. Inclusion of an exchange kernel in deriving the coupling-strength-dependent density–density response function leads to so-called τ-functionals, which – apart from a fourth-order Taylor series expansion – have only been realized in an approximate fashion so far to the best of our knowledge, most notably in the form of scaled σ-functionals. In this work, we derive, optimize, and benchmark three types of σ- and τ-functionals including approximate exchange effects in the form of an antisymmetrized Hartree kernel. These functionals, based on a second-order screened exchange type contribution in the adiabatic connection formalism, the electron–hole time-dependent Hartree–Fock kernel (eh-TDHF) otherwise known as RPA with exchange (RPAx), and an approximation thereof known as approximate exchange kernel (AXK), are optimized on the ASCDB database using two new parametrizations named A1 and A2. In addition, we report a first full evaluation of σ- and τ-functionals on the GMTKN55 database, revealing our exchange-including functionals to considerably outperform existing σ-functionals while being highly competitive with some of the best double-hybrid functionals of the original GMTKN55 publication. In particular, the σ-functionals based on AXK and τ-functionals based on RPAx with PBE0 reference stand out as highly accurate approaches for a wide variety of chemically relevant problems.

Großkopf, Johannes; Plaza, Manuel; Kutta, Roger Jan; Nuernberger, Patrick; Bach, Thorsten: Creating a Defined Chirality in Amino Acids and Cyclic Dipeptides by Photochemical Deracemization. Angew. Chem. Int. Ed. 62, 2023, e202313606

2,5-Diketopiperazines are cyclic dipeptides displaying a wide range of applications. Their enantioselective preparation has now been found possible from the respective racemates by a photochemical deracemization (53 examples, 74 % to quantitative yield, 71–99 % ee). A chiral benzophenone catalyst in concert with irradiation at λ = 366 nm enables to establish the configuration at the stereogenic carbon atom C6 at will. If other stereogenic centers are present in the diketopiperazines they remain unaffected and a stereochemical editing is possible at a single position. Consecutive reactions, including the conversion into N-aryl or N-alkyl amino acids or the reduction to piperazines, occur without compromising the newly created stereogenic center. Transient absorption spectroscopy revealed that the benzophenone catalyst processes one enantiomer of the 2,5-diketopiperazines preferentially and enables a reversible hydrogen atom transfer that is responsible for the deracemization process. The remarkably long lifetime of the protonated ketyl radical implies a yet unprecedented mode of action.

Kolb, Daniel; Almasalma, Ahmad A.; Morgenstern, Martin; Ganser, Leon; Weidacher, Isabel; Burkhard, König: Photocatalytic Dehydroformylation of Benzyl Alcohols to Arenes, ChemPhotoChem, 7, 2023, e20230016

The combination of photoinduced hydrogen atom transfer (HAT) and cobalt catalysis gives access to a mild dehydroformylation sequence for the defunctionalization of benzyl alcohols to arenes. The transformation proceeds through a stepwise radical pathway, wherein benzylic and acyl radicals are generated as key intermediates. As a result, stable C−C bonds can be cleaved while generating concomitant syngas (CO+H2).

Žurauskas, Jonas; Boháčová, Soňa; Wu, Shangze; Butera, Valeria; Schmid, Simon; Domański, Michal, Slanina, Tomáš; Barham, Joshua P.: Electron-Poor Acridones and Acridiniums as Super Photooxidants in Molecular Photoelectrochemistry by Unusual Mechanisms, Angew. Chem. Int. Ed. 62, 2023, e202307550

Under photoelectrochemical conditions, dicyanated acridones are precatalysts for acridinium ions as closed-shell, highly potent arene photooxidants. Despite the lifetime permitting diffusion-controlled quenching, a preassembly with substrate nonetheless operates. Highlighting the profound influence of preassembly on photocatalysis, quenching diverts from single to double electron transfer reduction of the excited state to an acridinide anion.

Schwinger, Daniel P., Pickl, Thomas; Bach, Thorsten: Photochemical Isomerization of Cyclohept-1-ene-1-carbaldehyde: Strain-Release Cycloadditions and Ene Reactions, J. Org. Chem.  88, 17, 2023, 12844–12852

Cyclohept-1-ene-1-carbaldehyde undergoes photoinduced EZ isomerization at λ = 350 nm. The ring strain facilitates Diels–Alder cycloaddiions with 1,3-dienes, [3 + 2] cycloadditions with 1,3-dipoles, and ene reactions with olefins. Products are trans-fused at the cycloheptane core and were obtained in yields of up to 82%. Single crystal X-ray analyses corroborated the constitution and relative configuration of key products. With BF3 as a Lewis acid and 2,3-dimethylbuta-1,3-diene, cyclohept-1-ene-1-carbaldehyde reacted in the dark and rearranged stereoselectively to a tricyclic ketone (87%).

Wylie, Luke; Barham, Joshua P., Kirchner, Barbara: Solvent Dependency of Catalyst-Substrate Aggregation Through π-π Stacking in Photoredox Catalysis, ChemPhysChem, 24, 2023, e202300470

The formation of photoredox catalyst assemblies on substrates is investigated using molecular dynamics via the angle, distance and longevity of the interactions. In addition, the solvent effect on these complex formations is also examined.

Ghosh, Indrajit; Shlapakov, Nikita; Karl, Tobias A.; Düker, Jonas; Nikitin, Maksim; Burykina, Julia V.; Ananikov, Valentine P.; König, Burkhard: General cross-coupling reactions with adaptive dynamic homogeneous catalysis chloroiodane-HFIP assemblies, Nature 14, 2023, 3907-3912

 

Cross-coupling reactions are among the most important transformations in modern organic synthesis1,2,3. Although the range of reported (het)aryl halides and nucleophile coupling partners is very large considering various protocols, the reaction conditions vary considerably between compound classes, necessitating renewed case-by-case optimization of the reaction conditions4. Here we introduce adaptive dynamic homogeneous catalysis (AD-HoC) with nickel under visible-light-driven redox reaction conditions for general C(sp2)–(hetero)atom coupling reactions. The self-adjustive nature of the catalytic system allowed the simple classification of dozens of various classes of nucleophiles in cross-coupling reactions. This is synthetically demonstrated in nine different bond-forming reactions (in this case, C(sp2)–S, Se, N, P, B, O, C(sp3, sp2, sp), Si, Cl) with hundreds of synthetic examples under predictable reaction conditions. The catalytic reaction centre(s) and conditions differ from one another by the added nucleophile, or if required, a commercially available inexpensive amine base.

Kolb, Daniel; Morgenstern, Martin; König, Burkhard: Decarbonylation of Benzaldehydes by Dual Photoorgano-Cobalt Catalysis, Chem. Commun., 59, 2023, 8592

We report a mild alternative to thermally-driven noble-metal catalyzed decarbonylation protocols for the defunctionalization of benzaldehydes in short reaction times. Our cooperative photocatalytic system involves thioxanthone as an inexpensive HAT-agent and a cobalt complex required for selective C(sp2)–C(sp2) bond cleavage. The generated acyl and phenyl intermediates are postulated to be stabilized as cobalt complexes.

Xu, Yi; Mewes, Lars; Thyrhaug, Erling; Sláma, Vladislav; Šanda, František; Langhans, Heinz; Hauer, Jürgen: Isolating Pure Donor and Acceptor Signals by Polarization-
Controlled Transient Absorption Spectroscopy, J. Chem. Phys. Lett. 14, 2023, 5390-5396

The optical spectra of molecules are often highly congested, inhibiting definite assignment of features and dynamics. In this work, we demonstrate and apply a polarization-based strategy for the decomposition of time-resolved optical spectra to analyze the electronic structure and energy transfer in a molecular donor−acceptor (D−A) dyad. We choose a dyad with orthogonal transition dipole moments for D and A and high fluorescence quantum yield to show that polarization-controlled ultrafast transient absorption spectra can isolate the pure D and A parts of the total signal. This provides a strategy to greatly reduce spectral congestion in complex systems and thus allows for detailed studies of electronic structure and electronic energy transfer.

Großkopf, Johannes; Heidecker, Alexandra H.; Bach, Thorsten: Photochemical Deracemization of 3-Substituted Oxindoles, Angew. Chem. Int. Ed. 62, 2023, e202305274

Racemic 3-substituted oxindoles were successfully converted into enantiomerically pure or enriched material (up to 99 % ee) upon irradiation at λ=366 nm in the presence of a chiral benzophenone catalyst (10 mol %). The photochemical deracemization process allows predictable editing of the stereogenic center at carbon atom C3. Light energy compensates for the associated loss of entropy and enables the decoupling of potentially reversible reactions, i.e. a hydrogen atom transfer to (photochemical) and from (thermal) the carbonyl group of the catalyst. The major enantiomer is continuously enriched in several catalytic cycles. The obtained oxindoles were shown to be valuable intermediates for further transformations, which proceeded with complete retention at the stereogenic center.

Chaibuth, Pawittra; Engl, Sebastian; Reichle, Alexander; Chainok, Kittipong; Sukwattanasinitt, Mongkol; Reiser, Oliver: In Situ Generated, Tetracoordinated Copper(II)-Quinoline Complexes as Photocatalysts for the Chlorosulfonylation of Alkenes and Alkynes, Adv. Synth.Catal., 365, 2023, 4701–4747

A series of copper complexes was synthesized and studied as photocatalysts for the chlorosulfonylation of olefins. Featuring a tetradentate ligand consisting of one amino quinoline and two methyl pyridine moieties, the resulting Cu(II)-complex is effective under visible light irradiation to add sulfonyl chlorides to alkenes and alkynes, including unactivated aliphatic olefins. A weak base additive such as Na2CO3 prevents catalyst poisoning, resulting in an improvement of reaction yields and catalyst lifetime. A broad scope of sulfonyl chlorides and alkenes/alkynes as coupling partners are amenable for the title process, including examples previously reported unsuccessful with established copper-based photocatalysts.

Harvey, Freya M.; Heidecker, Alexandra H.; Merten, Christian; Bach, Thorsten: Diastereoselective, Lewis acid-mediated Diels–Alder reactions of allenoic acid derivatives and 1,3-cyclopentadienes, Org. Biomol. Chem. 21, 2023, 4422–4428

Allenes with different substituents at their terminal carbon atom display axial chirality and can be obtained in enantiopure form by a photochemical deracemization protocol. It has now been studied under which conditions allenoic acid derivatives undergo a Diels–Alder reaction with 1,3-cyclopentadienes and which products result. Cyclic derivatives (lactams, lactones) underwent an exo-selective reaction catalyzed by the Lewis acid Eu(fod)3, while acyclic derivatives yielded with high preference the endo-products (EtAlCl2 as the preferred Lewis acid). The exocyclic double bond forms with exquisite diastereoselectivity and the chirality transfer is close to perfect. The method was applied to the synthesis of the sesquiterpenes β-santalol (1) and 10(E)-β-santalic acid (13).

Mandal, Tirtha; Katta, Narenderreddy; Paps, Hendrik; Reiser, Oliver: Merging Cu(I) and Cu(II) Photocatalysis: Development of a Versatile Oxohalogenation Protocol for the Sequential Cu(II)/Cu(I)-Catalyzed Oxoallylation of Vinylarenes, ACS Org. Inorg. Au, 3, 4, 2023, 171–176

A sequential photocatalytic strategy is developed via the merger of Cu(II)/Cu(I)-catalytic cycles for the oxoallylation of vinyl arenes via α-haloketones. The initial Cu(II)-photocatalyzed oxohalogenation exploits ligand-to-metal charge transfer (LMCT) to generate halide radicals from acyl halides utilizing air as a terminal oxidant and can be employed for the late-stage modification of pharmaceuticals and agrochemicals. α-Bromoketones obtained this way can be subsequently subjected to a one-pot Cu(I)-photocatalyzed allylation. This sequential photocatalysis proceeds in a highly regio- and chemoselective fashion and is inconsequential to the electronic nature of styrenes.

Leverenz, Malte; Brockmann, Hendrik; Dreuw, Andreas; Bach, Thorsten; Storch, Golo: Enantiodivergent Photochemical Rearrangements Due to Different Coordination Modes at an Oxazaborolidine Lewis Acid Catalyst, ACS Catal.  13, 2023, 9, 5896–5905

A strong enantiodivergence ranging from +92% ee to −45% ee was observed in the oxadi-π-methane rearrangement of 2,4-cyclohexadienones. Oxazaborolidine-based Lewis acid catalysts of the same absolute configuration were applied in all cases, and the stereochemical outcome is solely a function of the oxazaborolidine substituents. Based on the results of an extended catalyst library screening (27 examples) and by interrogating plausible catalyst–substrate complexes in the ground state with density functional theory (DFT) methods, we could link the switch in enantioselectivity to a change in substrate binding. If the typical substrate binding at the convex catalyst side is inhibited by bulky substituents, our results indicate that substrates instead bind to the concave side, and enantiomeric products result. Studies by TDDFT in the S1 excited state further clarified the mechanistic picture by connecting efficient product formation with trajectories that reach a conical intersection with more excess energy. Our analysis was validated by the stereochemical outcome achieved with five structurally different catalysts.

Wallach, Christoph; Selic, Yasmin; Geitner, Felix S.; Kumar, Ajeet; Thyrhaug, Erling; Hauer, Jürgen; Karttunen, Antti J.; Fässler, Thomas F.: Probing Charge-Transfer Processes in a Covalently Linked [Ge9]-Cluster Imine Dyad, Angew. Chem. Int. Ed. 62, 2023, e202304088

C60 donor dyads in which the carbon cage is covalently linked to an electron-donating unit have been discussed as one possibility for an electron-transfer system, and it has been shown that spherical [Ge9] cluster anions show a close relation to fullerenes with respect to their electronic structure. However, the optical properties of these clusters and of functionalized cluster derivatives are almost unknown. We now report on the synthesis of the intensely red [Ge9] cluster linked to an extended π-electron system. [Ge9{Si(TMS)3}2{CH3C=N}-DAB(II)Dipp] (1) is formed upon the reaction of [Ge9{Si(TMS)3}2]2− with bromo-diazaborole DAB(II)Dipp-Br in CH3CN (TMS=trimethylsilyl; DAB(II)=1,3,2-diazaborole with an unsaturated backbone; Dipp=2,6-di-iso-propylphenyl). Reversible protonation of the imine entity in 1 yields the deep green, zwitterionic cluster [Ge9{Si(TMS)3}2{CH3C=N(H)}-DAB(II)Dipp] (1-H) and vice versa. Optical spectroscopy combined with time- ependent density functional theory suggests a charge-transfer excitation between the cluster and the antibonding π* orbital of the imine moiety as the cause of the intense coloration. An absorption maximum of 1-H in the red region of the electromagnetic spectrum and the corresponding lowest-energy excited state at λ=669 nm make the compound an interesting starting point for further investigations targeting the design of photo-active cluster compounds.

Reichle, Alexander; Koch, Magdalena; Sterzel, Hannes; Großkopf, Lea-Joy; Floss, Johannes; Rehbein, Julia; Reiser, Oliver: Copper(I) Photocatalyzed Bromonitroalkylation of Olefins: Evidence for Highly Efficient Inner-Sphere Pathways, Angew. Chem. Int. Ed. 62, 2023, e202219086

Photocatalytic bromonitroalkylations of activated and unactivated olefins with broad scope become possible in the presence of CuI-photocatalysts. The key to success for this transformation is the highly efficient interaction of CuII with radical intermediates, which can even outperform a highly favorable cyclization of a transient to a persistent radical.

Kumar, Ajeet; Malevich, Pavel; Mewes, Lars; Wu, Shangze; Barham, Joshua P.; Hauer, Jürgen: Transient absorption spectroscopy based on uncompressed hollow core fiber white light proves pre-association between a radical ion photocatalyst and substrate, J. Chem. Phys. 158, 2023, 144201

We present a hollow-core fiber (HCF) based transient absorption experiment, with capabilities beyond common titanium:sapphire based setups. By spectral filtering of the HCF spectrum, we provide pump pulses centered at 425 nm with several hundred nJ of pulse energy at the sample position. By employing the red edge of the HCF output for seeding CaF2, we obtain smooth probing spectra in the range between 320 and 900 nm. We demonstrate the capabilities of our experiment by following the ultrafast relaxation dynamics of a radical cationic photocatalyst to prove its pre-association with an arene substrate, a phenomenon that was not detectable previously by steady-state spectroscopic techniques. The detected preassembly rationalizes the successful participation of radical ionic photocatalysts in single electron transfer reactions, a notion that has been subject to controversy in recent years.

Binder, Julia; Biswas, Aniruddha; Gulder, Tanja: Biomimetic chlorine-induced polyene cyclizations harnessing hypervalent chloroiodane-HFIP assemblies, Chem. Sci. 14, 2023, 3907-3912

 

While bromo- and iodocyclizations have recently been successfully implemented, the challenging chlorocyclizations have been scantly investigated. We present a selective and generally applicable concept of chlorination-induced polyene cyclization by utilizing HFIP–chloroiodane networks mimicking terpene cyclases. A manifold of different alkenes was converted with excellent selectivities (up to d.r. >95 : 5). The cyclization platform was even extended to several structurally challenging terpenes and terpenoid carbon frameworks.

Mandigma, Mark John P., Mattia; Stockerl; Kaur, Jaspreet; Barham, Joshua P.:Organophotocatalytic Mechanisms: Simplicity or Naïvety? Diverting Reactive Pathways by Modifications of Catalyst Structure, Redox States and Substrate Preassemblies, ChemCatChem 15, 2023, e202201542

Photocatalysis is a powerful tool to assemble diverse chemical scaffolds, yet a bottleneck on its further development is the understanding of the multitude of possible pathways when practitioners rely only on oversimplified thermodynamic and optical factors. Recently, there is a growing number of studies in the field that exploit, inter alia, kinetic parameters and organophotocatalysts that are synthetically more programmable in terms of their redox states and opportunities for aggregation with a target substrate. Non-covalent interactions play a key role that enables access to a new generation of reactivities such as those of open-shell organophotocatalysts. In this review, we discuss how targeted structural and redox modifications influence the organophotocatalytic mechanisms together with their underlying principles. We also highlight the benefits of strategies such as preassembly and static quenching that overcome common reactivity issues (e. g., diffusion rate limits and energetic limits).

Ritu, Ritu; Kolb, Daniel; Jain, Nidhi; König, Burkhard: Synthesis of Linear Enamides and Enecarbamates via Photoredox Acceptorless Dehydrogenation, Adv. Synth. Catal. 365, 2023, 605–611.

In recent years, several methods for the direct desaturation of aliphatic compounds have been developed, facilitated by the unique combination of photoredox and transition-metalcatalysis. Hereby, alkenes with high functionalizationpotential can be prepared in a straight forward fashion. We adapted a previously reported system involving tetrabutylammoniumdecatungstate (TBADT) as hydrogen atom transfer (HAT) agent and a cobaloxime co-catalyst for dihydrogen evolution for the dehydrogenative preparation of linear enamides and enecarbamates from saturated precursors. The substrate scope includes severa lnatural products and drug derivatives. The reaction does not require noble metal catalysts, exhibits short reaction times compared to previous methods and is suitable for the late stage functionalization of drug derivatives.

Arnold, Andreas M.; Dullinger, Philipp; Biswas, Aniruddha; Jandl, Christian; Horinek, Dominik; Gulder, Tanja: Enzyme-like polyene cyclizations catalyzed by dynamic, self-assembled, supramolecular fluoro alcohol-amine clusters, Nat Commun 14, 2023, 813 

Terpene cyclases catalyze one of the most powerful transformations with respect to efficiency and selectivity in natural product (bio)synthesis. In such polyene cyclizations, structurally highly complex carbon scaffolds are built by the controlled ring closure of linear polyenes. Thereby, multiple C,C bonds and stereocenters are simultaneously created with high precision. Structural preorganization of the substrate carbon chain inside the active center of the enzyme is responsible for the product- and stereoselectivity of this cyclization. Here, we show that in-situ formed fluorinated-alcohol-amine supramolecular clusters serve as artificial cyclases by triggering enzyme-like reactivity and selectivity by controlling substrate conformation in solution. Because of the dynamic nature of these supramolecular assemblies, a broad range of terpenes can be produced diastereoselectively. Mechanistic studies reveal a finely balanced interplay of fluorinated solvent, catalyst, and substrate as key to establishing nature’s concept of a shape-selective polyene cyclization in organic synthesis.

Reichle, Alexander; Reiser, Oliver: Light-induced homolysis of copper(II)-complexes – a perspective for photocatalysis, Chem. Sci., 14, 2023, 4449

 

 

Over the past decade, photocatalysis has developed into a powerful strategy for the selective functionalization of molecules through radical intermediates. Besides the well-established iridium- or ruthenium-based photocatalysts, which ideally fulfill the requirements for a photocatalyst, such as long excited-state lifetimes and photostability, the shift towards earth-abundant metal-based photocatalysts has so far been less explored. The concept of light-induced homolysis (LIH) for generating radicals has recently gained significant interest as a new platform for inducing photoreactions with earth-abundant 3d-metal complexes despite only having excited-state lifetimes in the low nanosecond range or even below. Cu(II)-complexes play a prominent role in exploiting this concept, which will be discussed by showcasing recent developments in organic synthesis with a view to identifying the future prospects of this growing field.

Tian, Ya-Ming; Hofmann, Evamaria; Silva, Wagner; Pu, Xiang; Touraud, Didier; Gschwind, Ruth M.; Kunz, Werner; König, Burkhard: Enforced Electronic-Donor-Acceptor Complex Formation in Water for Photochemical Cross-Coupling, Angew. Chem. Int. Ed. 62, 17, 2023, e202218775

 

The amino alcohol meglumine solubilizes organic compounds in water and enforces the formation of electron donor acceptor (EDA) complexes of haloarenes with indoles, anilines, anisoles or thiols, which are not observed in organic solvents. UV-A photoinduced electron transfer within the EDA complexes induces the mesolytic cleavage of the halide ion and radical recombination of the arenes leading, after rearomatization and proton loss to C−C or C−S coupling products. Depending on the substitution pattern selective and unique cross-couplings are observed. UV and NMR measurements reveal the importance of the assembly for the photoinduced reaction. Enforced EDA aggregate formation in water allows new activation modes for organic photochemical synthesis.

Reichle, Alexander; Koch, Magdalena; Sterzel, Hannes; Großkopf, Lea-Joy; Floss, Johannes; Rehbein, Julia; Reiser, Oliver: Copper(I) Photocatalyzed Bromonitroalkylation of Olefins: Evidence for Highly Efficient Inner-Sphere Pathways, Angew. Chem. Int. Ed. 62, 2023, e202219086

We report the visible light-mediated coppercatalyzed vicinal difunctionalization of olefins utilizing bromonitroalkanes as ATRA reagents. This protocol is characterized by high yields and fast reaction times under environmentally benign reaction conditions with exceptional scope, allowing the rapid functionalization of both activated and unactivated olefins. Moreover, late-stage functionnalization of biologically active molecules and upscaling to gram quantities is demonstrated, which offers manifold possibilities for further transformations, e.g. access to nitro- and aminocyclopropanes. Besides the synthetic utility of the title transformation, this study undergirds the exclusive role of copper in photoredox catalysis showing its ability to stabilize and interact with radical intermediates in its coordination sphere. EPR studies suggest that such interactions can even outperform a highly favorable cyclization of transient to persistent radicals contrasting iridium-based photocatalysts.

Kutta, Roger J.; Großkopf, Johannes; van Staalduinen, Nils; Seitz, Antonia; Pracht, Philipp; Breitenlechner, Stefan; Bannwarth, Christoph; Nuernberger, Patrick; Bach, Thorsten: Multifaceted View on the Mechanism of a Photochemical Deracemization Reaction, J. Am. Chem. Soc. 145, 2023, 2354-2363 

Upon irradiation in the presence of a chiral benzophenone catalyst (5 mol %), a racemic mixture of a given chiral imidazolidine-2,4-dione (hydantoin) can be converted almost quantitatively into the same compound with high enantiomeric excess (80–99% ee). The mechanism of this photochemical deracemization reaction was elucidated by a suite of mechanistic experiments. It was corroborated by nuclear magnetic resonance titration that the catalyst binds the two enantiomers by two-point hydrogen bonding. In one of the diastereomeric complexes, the hydrogen atom at the stereogenic carbon atom is ideally positioned for hydrogen atom transfer (HAT) to the photoexcited benzophenone. Detection of the protonated ketyl radical by transient absorption revealed hydrogen abstraction to occur from only one but not from the other hydantoin enantiomer. Quantum chemical calculations allowed us to visualize the HAT within this complex and, more importantly, showed that the back HAT does not occur to the carbon atom of the hydantoin radical but to its oxygen atom. The achiral enol formed in this process could be directly monitored by its characteristic transient absorption signal at λ ≅ 330 nm. Subsequent tautomerization leads to both hydantoin enantiomers, but only one of them returns to the catalytic cycle, thus leading to an enrichment of the other enantiomer. The data are fully consistent with deuterium labeling experiments and deliver a detailed picture of a synthetically useful photochemical deracemization reaction.

Birnthaler, Dominik; Narobe, Rok; Lopez-Berguno, Eliseo; Haag, Christoph; König, Burkhard: M Synthetic Application of Bismuth LMCT Photocatalysis in Radical Coupling Reactions, ACS Catal. 13, 2023, 1125-1132 

Ligand-to-metal charge transfer (LMCT) photocatalysis allows the activation and synthetic utilization of halides and other heteroatoms in metal complexes. Many metals are known to undergo LMCT but so far remain underutilized in the field of catalysis. A screening assay identifying LMCT activity helped us to expand this catalysis concept to the application of bismuth LMCT in organic radical coupling reactions. We demonstrate its application for the generation of two different radicals (chlorine and carboxyl) in net-oxidative as well as redox-neutral photochemical reactions. Detailed investigation of the model Giese-type coupling revealed BiCl4 and BiCl52– as catalytically active bismuth species under 385 nm irradiation. Combined cyclic voltammetry and UV–vis studies gave insight into the reactivity of the highly reactive bismuth(II) catalyst fragment.

Petek, Nejc; Brodnik, Helena; Reiser, Oliver; Štefane, Bogdan: Copper- and Photoredox-Catalyzed Cascade to Trifluoromethylated Divinyl Sulfones, J. Org. Chem. 88, 10, 2023, 6538–6547

A Cu(I)-photoredox-catalyzed trifluoromethylchlorosulfonylation reaction of terminal alkynes under visible light conditions was developed, giving rise to trifluoromethyl-substituted vinylsulfonyl chlorides, which can subsequently be coupled to a second alkyne under photocatalytic conditions. The transformation proceeds with high regio- and stereoselectivity and can be applied to aliphatic and aromatic alkynes with various functional groups. Trifluoromethyl-substituted divinyl sulfones prepared by this protocol can be readily used as synthetically valuable intermediates as demonstrated with various postmodification examples.

More Publications

Tian, Xianhai; Liu, Yuliang; Yakubov, Shahboz; Schütte, Jonathan; Chiba, Shunsuke; Barham, Joshua P.: Photo- and electro-chemical strategies for the activations of strong chemical bonds, Chem. Soc. Rev., 53, 2024, 263

The employment of light and/or electricity – alternatively to conventional thermal energy – unlocks new reactivity paradigms as tools for chemical substrate activations. This leads to the development of new synthetic reactions and a vast expansion of chemical spaces. This review summarizes recent developments in photo- and/or electrochemical activation strategies for the functionalization of strong bonds...

Großkopf, Johannes; Bach, Thorsten: Catalytic Photochemical Deracemization via Short‐Lived Intermediates. Angew. Chem. Int. Ed. 62, 2023, e202308241

Photochemical deracemization offers a unique opportunity to directly obtain enantiopure compounds from their racemates. Short-lived intermediates play a key role in the enantioselectivity-determining step. The review covers comprehensively the research performed in the area and discusses current developments.

 

Lepori, Mattia; Stockerl; Schmid, Simon; Barham, Joshua P.: Photoredox catalysis harvesting multiple photon or electrochemical energies, Beilstein J. Org. Chem. 19,  2023, 1055-1145

Photoredox catalysis (PRC) is a cutting-edge frontier for single electron-transfer (SET) reactions, enabling the generation of reactive intermediates for both oxidative and reductive processes via photon activation of a catalyst. Although this represents a significant step towards chemoselective and, more generally, sustainable chemistry, its efficacy is limited by the energy of visible light photons. Nowadays, excellent alternative conditions are available to overcome these limitations, harvesting two different but correlated concepts: the use of multi-photon processes such as consecutive photoinduced electron transfer (conPET) and the combination of photo- and electrochemistry in synthetic photoelectrochemistry (PEC). Herein, we review the most recent contributions to these fields in both oxidative and reductive activations of organic functional groups. New opportunities for organic chemists are captured, such as selective reactions employing super-oxidants and super-reductants to engage unactivated chemical feedstocks, and scalability up to gram scales in continuous flow. This review provides comparisons between the two techniques (multi-photon photoredox catalysis and PEC) to help the reader to fully understand their similarities, differences and potential applications and to therefore choose which method is the most appropriate for a given reaction, scale and purpose of a project.

2022

Publications

Artmann, Kevin; Pollok, Corina H.; Merten, Christian; Nuernberger, Patrick: Wavelength-dependent photochemistry of a salicylimine derivative studied with cryogenic and ultrafast spectroscopy approaches, Phys. Chem. Chem. Phys. 24, 2022, 30017-30026 

Salicylimines are versatile compounds in which an excited-state intramolecular proton transfer and torsional motions may set in upon photoexcitation. Here, we study N-(α-phenylethyl)salicylimine (PESA) to elucidate how the photochemical reaction pathways depend on the excitation wavelength and to what extent the relative photoproduct distribution can be steered towards a desired species. DFT structure and potential energy calculations disclose that the most stable ground-state conformer is an enol species and that the photodynamics may proceed differently depending on the excited state that is reached. With matrix isolation infrared spectroscopy, the predominance of the enol conformer of PESA is confirmed. Illumination of the cryogenic sample with different wavelengths shifts the ratio of enol and keto products, and by sequential irradiation a selective re- and depopulation is possible. Femtosecond transient absorption spectroscopy further reveals that also at room temperature, the outcome of the photoreaction depends on excitation wavelength, and in combination with the calculations, it can be rationalized that the decisive step occurs within the first hundred femtoseconds. Since the ultrafast dynamics mostly match those of similar salicylimines, our findings might also apply to those systems and provide additional insight into their reported sensitivity on excitation energy.

Rigotti, Thomas; Bach, Thorsten: Bicyclo[2.1.1]hexanes by Visible Light-Driven Intramolecular Crossed [2 + 2] Photocycloadditions, Org. Lett. 24, 2022, 8821-8825

Bicyclo[2.1.1]hexanes have become increasingly popular building blocks in medicinal chemistry as bridged scaffolds that provide unexplored chemical space. We herein report a visible light-driven approach to these compounds that relies on an intramolecular crossed [2 + 2] photocycloaddition of styrene derivatives enabled by triplet energy transfer. Bicyclo[2.1.1]hexanes were obtained in good to high yields (19 examples, 61%-quantitative yield) and allowed for further functionalizations by consecutive reactions, thereby opening different pathways to decorate the aliphatic core structure.

Yakubov, Shahboz; Stockerl, Willibald J.; Tian, Xianhai; Shahin, Ahmed; Mandigma, Mark John P.; Gschwind, Ruth M.; Barham, Joshua P.: Benzoates as photosensitization catalysts and auxiliaries in efficient, practical, light-powered direct C(sp3)—H fluorinations, Chem. Sci. 13, 2022, 14041-14051

Of the methods for direct fluorination of unactivated C(sp3)–H bonds, photosensitization of SelectFluor is a promising approach. Although many substrates can be activated with photosensitizing catalysts, issues remain that hamper fluorination of complex molecules. Alcohol- or amine-containing functional groups are not tolerated, fluorination regioselectivity follows factors endogenous to the substrate and cannot be influenced by the catalyst, and reactions are highly air-sensitive. We report that benzoyl groups serve as highly efficient photosensitizers which, in combination with SelectFluor, enable visible light-powered direct fluorination of unactivated C(sp3)–H bonds. Compared to previous photosensitizer architectures, the benzoyls have versatility to function both (i) as a photosensitizing catalyst for simple substrate fluorinations and (ii) as photosensitizing auxiliaries for complex molecule fluorinations that are easily installed and removed without compromising yield. Our auxiliary approach (i) substantially decreases the reaction's induction period, (ii) enables C(sp3)–H fluorination of many substrates that fail under catalytic conditions, (iii) increases kinetic reproducibility, and (iv) promotes reactions to higher yields, in shorter times, on multigram scales, and even under air. Observations and mechanistic studies suggest an intimate ‘assembly’ of auxiliary and SelectFluor prior/after photoexcitation. The auxiliary allows other EnT photochemistry under air. Examples show how auxiliary placement proximally directs regioselectivity, where previous methods are substrate-directed.

Jurberg, Igor D.; Nome, Rene A.; Crespi, Stefano; Atvars, Teresa D. Z.; König, Burkhard: Visible Light-Enhanced C—H Amination of Cyclic Ethers with Iminoiodinanes, Adv.Synth. Catal. 364, 2022, 4061-4068 

A two-step protocol allowing the C−H amination of cyclic ethers with iminoiodinanes, followed by the reduction of the resulting intermediate has been developed for the preparation of amino alcohols. The initial C−H functionalization is accelerated by visible light, improving the reactivity compared to the thermal process performed in the dark. The effect of different substituents on the photochemical reactivity of iminoiodinanes has been studied both experimentally and computationally. Photophysical measurements and DFT calculations were performed to better understand the observed reactivities and corroborate the proposed mechanistic proposal.

Wang, Hua; Wang, Shun; George, Vincent; Llorente, Galder; König, Burkhard: Photo-Induced Homologation of Carbonyl Compounds for Iterative Syntheses, Angew. Chem. Int. Ed. 61, 2022, e202211578

A photo-induced Büchner-Curtius-Schlotterbeck type reaction for carbonyl homologation is described. The protocol allows the use of carbonyl compounds as safe and readily available diazo precursors through direct photoexcitation of corresponding N-tosylhydrazone anions. Functionalized aliphatic aldehydes and ketones are prepared in a practical and iterative manner.

Schwinger, Daniel P.; Peschel, Martin T.; Rigotti, Thomas; Kabaciński, Piotr; Knoll, Thomas; Thyrhaug, Erling; Cerullo, Giulio; Hauer, Jürgen; de Vivie-Riedle, Regina; Bach, Thorsten: Photoinduced B–Cl Bond Fission in Aldehyde-BCl3 Complexes as a Mechanistic Scenario for C–H Bond Activation, J. Am. Chem. Soc. 144, 2022, 18927-18937

In concert with carbonyl compounds, Lewis acids have been identified as a versatile class of photocatalysts. Thus far, research has focused on activation of the substrate, either by changing its photophysical properties or by modifying its photochemistry. In this work, we expand the established mode of action by demonstrating that UV photoexcitation of a Lewis acid–base complex can lead to homolytic cleavage of a covalent bond in the Lewis acid. In a study on the complex of benzaldehyde and the Lewis acid BCl3, we found evidence for homolytic B–Cl bond cleavage leading to formation of a borylated ketyl radical and a free chlorine atom only hundreds of femtoseconds after excitation. Both time-dependent density functional theory and transient absorption experiments identify a benzaldehyde-BCl2 cation as the dominant species formed on the nanosecond time scale. The experimentally validated B–Cl bond homolysis was synthetically exploited for a BCl3-mediated hydroalkylation reaction of aromatic aldehydes (19 examples, 42–76% yield). It was found that hydrocarbons undergo addition to the C═O double bond via a radical pathway. The photogenerated chlorine radical abstracts a hydrogen atom from the alkane, and the resulting carbon-centered radical either recombines with the borylated ketyl radical or adds to the ground-state aldehyde-BCl3 complex, releasing a chlorine atom. The existence of a radical chain was corroborated by quantum yield measurements and by theory. The photolytic mechanism described here is based on electron transfer between a bound chlorine and an aromatic π-system on the substrate. Thereby, it avoids the use of redox-active transition metals.

Chinchole, Anurag; Henriquez, Marco A.; Cortes-Arriagada, Diego; Cabrera, Alan R.; Reiser, Oliver: Iron(III)-Light-Induced Homolysis: A Dual Photocatalytic Approach for the Hydroacylation of Alkenes Using Acyl Radicals via Direct HAT from Aldehydes, ACS Catal. 12, 2022, 13549-13554

A dual photocatalytic protocol was developed to generate acyl radicals from readily available aldehydes via hydrogen atom transfer (HAT). Synergistic cooperation, being supported by DFT studies, between earth-abundant iron(III)chloride and 9,10-diphenylanthracene (DPA) to activate the aldehyde for a HAT step proved to be an efficient, economic, and green route for the hydroacylation of electron-deficient alkenes under UV-light irradiation with broad functional group compatibility. This methodology can be conveniently scaled up and applied to produce valuable materials from renewable feedstock chemicals.

Katta, Narenderreddy; Zhao, Quan-Qing; Mandal, Tirtha; Reiser, Oliver: Divergent and Synergistic Photocatalysis: Hydro- and Oxoalkylation of Vinyl Arenes for the Stereoselective Synthesis of Cyclopentanols via a Formal [4+1]-Annulation of 1,3-Dicarbonyls, ACS Catal. 12, 2022, 14398-14407

The controllable divergent reactivity of 1,3-dicarbonyls is described, which enables the efficient hydro- and oxoalkylation of vinyl arenes. Both reaction pathways are initiated through the formation of polarity-reversed C-centered-radical intermediates at the active methylene center of 1,3-dicarbonyls via direct photocatalytic C–H bond transformations. The oxoalkylation of alkenes is achieved under aerobic conditions via a Cu(II)-photomediated rebound mechanism, while the corresponding hydroalkylation becomes possible under a nitrogen atmosphere by the combination of 4CzIPN and a Brønsted base. The breadth of these divergent protocols is demonstrated in the late-stage modification of drugs and natural products and by the transformation of the products to a variety of heterocycles such as pyridines, pyrroles, or furans. Moreover, the two catalytic modes can be combined synergistically for the stereoselective construction of cyclopentanol derivatives in a formal [4+1]-annulation process.

Park, Sooyoung; Dutta, Amit K.; Allacher, Carina; Abramov, Anton; Dullinger, Philipp; Kuzmanoska, Katerina; Fritsch, Daniela; Hitzfeld, Patrick; Horinek, Dominik; Rehbein, Julia; Nuernberger, Patrick; Gschwind, Ruth M.; Breder, Alexander: Hydrogen-Bond-Modulated Nucleofugality of SeIII Species to Enable Photoredox-Catalytic Semipinacol Manifolds, Angew. Chem. Int. Ed. 61, 2022, e202208611

Chemical bond activations mediated by H-bond interactions involving highly electronegative elements such as nitrogen and oxygen are powerful tactics in modern catalysis research. On the contrary, kindred catalytic regimes in which heavier, less electronegative elements such as selenium engage in H-bond interactions to co-activate C−Se σ-bonds under oxidative conditions are elusive. Traditional strategies to enhance the nucleofugality of selenium residues predicate on the oxidative addition of electrophiles onto SeII-centers, which entails the elimination of the resulting SeIV moieties. Catalytic procedures in which SeIV nucleofuges are substituted rather than eliminated are very rare and, so far, not applicable to carbon-carbon bond formations. In this study, we introduce an unprecedented combination of O−H⋅⋅⋅Se H-bond interactions and single electron oxidation to catalytically generate SeIII nucleofuges that allow for the formation of new C−C σ-bonds by means of a type I semipinacol process in high yields and excellent selectivity.

Stegbauer, Simone; Jandl, Christian; Bach, Thorsten: Chiral Lewis acid catalysis in a visible light-triggered cycloaddition/rearrangement cascade, Chem. Sci. 13, 2022, 11856-11862.

Cascade (domino) reactions facilitate the formation of complex molecules from simple starting materials in a single operation. It was found that 1-naphthaldehyde derivatives can be converted to enantioenriched (82–96% ee) polycyclic benzoisochromenes via a cascade of ortho photocycloaddition and ensuing acid-catalysed rearrangement reactions. The cascade was initiated by irradiation with visible light (λ = 457 nm) and catalysed by a chiral AlBr3-activated 1,3,2-oxazaborolidine (14 examples, 65–93% yield). The absolute configuration of the products was elucidated by single crystal X-ray crystallography. Mechanistic experiments suggest that the ortho photocycloaddition occurs on the triplet hypersurface and that the chiral catalyst induces in this step the observed enantioselectivity.

Wang, Huaiju; Tian, Ya-Ming; König, Burkhard: Energy- and atom-efficient chemical synthesis with endergonic photocatalysis, Nat. Rev. Chem. 6, 2022, 745-755

Endergonic photocatalysis is the use of light to perform catalytic reactions that are thermodynamically unfavourable. While photocatalysis has become a powerful tool in facilitating chemical transformations, the light-energy efficiency of these processes has not gathered much attention. Exergonic photocatalysis does not take full advantage of the light energy input, producing low-energy products and heat, whereas endergonic photocatalysis incorporates a portion of the photon energy into the reaction, yielding products that are higher in free energy than the reactants. Such processes can enable catalytic, atom-economic syntheses of reactive compounds from bench-stable materials. With respect to environmental friendliness and carbon neutrality, endergonic photocatalysis is also of interest to large-scale industrial manufacturing, where better energy efficiency, less waste and value addition are highly sought. We therefore assess here the thermochemistry of several classes of reported photocatalytic transformations to showcase current advances in endergonic photocatalysis and point to their industrial potential.

Ritu; Das, Saikat; Tian, Ya-Ming; Karl, Tobias; Jain, Nidhi; König, Burkhard: Photocatalyzed Dehydrogenation of Aliphatic N‑Heterocycles Releasing Dihydrogen, ACS Catal. 12, 2022, 10326–10332

We report the iridium–nickel dual photocatalytic acceptorless and redox neutral dehydrogenation of aliphatic heterocycles yielding cyclic alkenes without overoxidation at room temperature. Excitation of the iridium photocatalyst initiates the formation of a nickel hydride intermediate that yields alkenes and H2 via β-hydride elimination. The reaction proceeds regioselectively and the scope was demonstrated by the synthesis of 12 biologically relevant molecules and drugs. In addition, commercially and easily available N-heterocyclic alkane starting materials were converted into functionalized alkenes of high synthetic and commercial value using the method.

Lemke, Yannick; Graf, Daniel; Kussmann, Jörg; Ochsenfeld, Christian: An assessment of orbital energy corrections for the direct random phase approximation and explicit σ-functionals, Mol. Phys., 2022, e2098862. doi: 10.1080/00268976.2022.2098862

The σ-functionals developed in the Görling group [J. Chem. Phys. 154, 014104 (2021); ibid. 155, 134111 (2021)] facilitate impressive improvements over the direct random phase approximation (dRPA) and provide chemical accuracy for a broad spectrum of benchmarks concerning reaction energies and barrier heights, but struggle considerably with problems related to self-interaction. We herein assess two possible corrections to the orbital energies in the construction of the noninteracting response function for the dRPA and σ-functionals: (i) The scaling corrections of Yang and co-workers, which have been successfully applied within DFT, and (ii) the admixture of exact exchange in a post-SCF fashion similar to some double-hybrid functionals. An analysis of static shifts to the virtual orbital energies reveals the choice of corrections to be a difficult balancing act, as the effect of the corrections vastly differs between benchmark sets. Scaling corrections are found to provide substantial improvements to self-interaction problems, but seem adversarial for thermochemistry in combination with RPA. The post-SCF inclusion of exact exchange in combination with a semicanonical projection is shown to retain the accuracy of σ-functionals over a wide range of exact exchange admixtures and reduces the computational cost of the SCF calculation compared to hybrid functionals, but provides smaller improvements to self-interaction problems than scaling corrections for the most challenging cases.

Narobe, Rok; Murugesan, Kathiravan; Haag, Christoph; Schimer, Tobias Emanuel; König, Burkhard: C(sp3)-H Ritter amination by excitation of in situ generated iodine(III)-BF3 complexes, Chem. Commun 58, 2022, 8778-8781

Visible light excitation of a hypervalent iodine (III)-BF3 complex enables the formation of carbocations from C(sp3)–H bonds. The complex is generated catalytically from a iodoarene, a carboxylate ligand, an oxidizing agent (Selectfluor) and the Lewis acid BF3. This modular catalytic system allowed us to conveniently screen performance of different in situ formed complexes. Their excitation leads to hydrogen abstraction from the C(sp3)–H precursor which is followed by a rapid oxidation of the formed carbon radical to give carbocationic intermediates. These were reacted in a Ritter-type amination to give access to synthetically valuable amine derivatives. Moreover, the method is practically simple and based on readily available chemicals.

Jeremias, Noah; Peschel, Martin T.; Jaschke, Constantin; de Vivie-Riedle, Regina; Bach, Thorsten: Photochemical Ring Contraction of 5,5-Dialkylcyclopent-2-enones and in situ Trapping by Primary Amines, J. Org. Chem. 88, 10, 2023, 6294–6303

If substituted in the 5,5-position, cyclopent-2-enones undergo a smooth photochemical rearrangement to ketenes. A concomitant cyclopropane formation occurs due to a 1,3-shift of the C5 carbon atom from the carbonyl carbon atom (C1) to carbon atom C3. In this study, the cyclopropyl-substituted ketene intermediates were trapped in situ by primary amines providing an efficient entry into 2,2-disubstituted cyclopropaneacetic amides (24 examples, 49–95% yield). A remarkable feature of the reaction is the fact that the photochemical rearrangement can occur from either the first excited singlet (S1) or the respective triplet state (T1). In line with experimental results (triplet quenching, sensitization), XMS-CASPT2 calculations support the existence of efficient reaction pathways to the intermediate ketene both on the singlet and on the triplet hypersurface.

Lemke Y.; Kussmann J.; Ochsenfeld, C.: Efficient Integral-Direct Methods for Self-Consistent Reduced Density Matrix Functional Theory Calculations on Central and Graphics Processing Units, J. Chem. Theory Comput. 18, 2022, 4229-4244

Reduced density matrix functional theory (RDMFT), a promising direction in the problem of describing strongly correlated systems, is currently limited by its explicit dependence on natural orbitals and, by extension, the costly need to construct two-electron integrals in the molecular orbital basis. While a resolution-of-the-identity approach can reduce the asymptotic scaling behavior from O(N5) to O(N4), this is still prohibitively expensive for large systems, especially considering the usually slow convergence and the resulting high number of orbital optimization steps. In this work, efficient integral-direct methods are derived and benchmarked for various approximate functionals. Furthermore, we show how these integral-direct methods can be integrated into existing self-consistent energy minimization frameworks in an efficient manner, including improved methods for calculating diagonal elements of the two-electron integral tensor as required in self-interaction-corrected functionals and second derivatives of the energy with respect to the occupation numbers. In combination, these methods provide speedups of up to several orders of magnitude while greatly diminishing memory requirements, enabling the application of RDMFT to large molecular systems of general chemical interest, such as the challenging triplet–quintet gap of the iron(II) porphyrin complex.

Tian, Xianhai; Kaur, Jaspreet; Yakubov, Shahboz; Barham, Joshua P.: α-Amino Radical Halogen Atom Transfer Agents for Metallaphotoredox-Catalyzed Cross-Electrophile Couplings of Distinct Organic Halides, ChemSusChem 15, 2022, e202200906

Cross coupling: A practical dual Ni/photoredox catalyzed cross-electrophile coupling of organic halides by employing readily available α-amino radicals as halogen atom transfer agents is reported. Both coupling partners can be flexibly chosen as limiting reactant to forge 6 different types of C−C bond for a broad scope of applications (>70 examples) including late-stage functionalizations of pharmaceutical compounds. The reaction is scalable in batch and continuous flow.

Schwinger, Daniel P.; Peschel, Martin T.; Jaschke, Constantin; Jandl, Christian; de Vivie-Riedle, Regina; Bach, Thorsten: Diels–Alder Reaction of Photochemically Generated (E)-Cyclohept-2-enones: Diene Scope, Reaction Pathway, and Synthetic Application. J. Org. Chem. 87, 2022, 4838–4851

Cyclohept-2-enone undergoes isomerization upon irradiation with UV light to its (E)-isomer, which exhibits significant ring strain. XMS-CASPT2 calculations revealed that this process can proceed on both the singlet and triplet hypersurface. (E)-Cyclohept-2-enone can undergo a Diels-Alder reaction with different dienes at room temperature, yielding trans-fused six-membered rings (up to 98% yield). In case of cyclic dienes, the exo-product was the major isomer in most cases. The Diels-Alder reaction with furan was studied in greater detail. Experimental and theoretical outcome via DLPNO-CCSD(T) calculations matched and the relative configuration of the diastereomers was corroborated via X-ray analysis. Other cyclic enones were also successfully employed. In the end, the method was applied to the total synthesis of racemic trans-α-himachalene.

Foja, Richard; Walter, Alexandra; Jandl, Christian; Thyrhaug, Erling; Hauer, Jürgen; Storch, Golo: Reduced molecular flavins as one-electron reducing agents after photoexcitation. J. Am. Chem. Soc. 144 (11), 2022, 4721-4726

Flavoenzymes are involved in a multitude of chemical reactions and the cofactor can act as the catalytically active species in different oxidation states. While (photo)oxidation reactions with molecular flavins are established, no report of reduced, molecular flavins in the conversion of organic substrates are available. We report a catalytic method using reduced, molecular flavins as photoreductants and γ-terpinene as sacrificial reductant. A design for air-stable, reduced flavins using a conformational bias strategy is presented and circumvents rapid reduction of O2 from air. Using our catalytic strategy, we were able to perform a 5-exo-trig cyclization of barbituric acid derivatives, effectively replacing SmI2 as a reductant for this reaction. Such flavin catalyzed reductions are anticipated to be beneficial for other transformations and other reactivities are highlighted in this publication.

Kumar, Manoj; Verma, Shalini, Verma; Mishra, Vivek; Reiser, Oliver; Verma, Akhilesh K.: Visible-Light-Accelerated Copper-Catalyzed [3 + 2] Cycloaddition of N-Tosylcyclopropylamines with Alkynes/Alkenes, J. Org. Chem. 87, 2022, 6263-6272

Copper-catalyzed [3+2] cycloadditions of N-tosylcyclopropylamine with alkynes and alkenes have been accomplished under visible light irradiation. The developed approach is compatible with a range of functionalities and allows the synthesis of diversified aminated cyclopentene and cyclopentane derivatives being relevant for drug synthesis. The protocol is operationally simple and economically affordable as it does not require any ligand, base, or additives. As the key step, the one-electron oxidation of the N-tosyl moiety by visible light-induced homolysis of a transient Cu(II)-tosylamide complex is proposed, providing a facile entry for N-centered radicals.

Reichle, Alexander; Sterzel, Hannes; Kreitmeier, Peter; Fayad, Remi; Castellano, Felix N.; Rehbein, Julia; Reiser, Oliver: Copper(II)-photocatalyzed decarboxylative oxygenation of carboxylic acids, Chem. Commun. 58, 2022, 4456-4459

Showcasing the concept of light-induced homolysis for the generation of radicals, the CuII-photocatalyzed decarboxylative oxygenation of carboxylic acids with molecular oxygen as the terminal oxidant is described. Two CuII-carboxylate complexes with different coordination geometries were synthesized and characterized by X-ray analysis, correlating their structure with their ability to initiate light-induced decarboxylations.

Zhao, QuanQing; Rehbein, Julia; Reiser, Oliver: Thermoneutral synthesis of spiro-1,4- cyclohexadienes by visible-light-driven dearomatization of benzylmalonates: Green Chem. 24, 2022, 2772-2776

The inherent aromaticity of aromatic compounds, especially unactivated aromatic compounds, render them challengeable to undergo dearomatization process. We report here the dearomatizative coupling of benzylmalonates and alkynes to spiroanellated 1,4-cyclohexadienes, which proceeds via activation with visible light with perfect atom economy in high yields (up to 98%). In this protocol, no preactivation of the substrates or employment of stoichiometric high energy reagents, being the traditional approach to drive thermoneutral transformations, is necessary. Calculations suggest that the overall process is approximately thermoneutral, showcasing the special opportunities of light-driven processes to develop sustainable transformations that defy thermodynamic requirements.

Rigotti, Thomas; Schwinger, Daniel P.; Graßl, Raphaela; Jandl, Christian; Bach, Thorsten: Enantioselective Crossed Intramolecular [2+2] Photocycloaddition Reactions Mediated by a Chiral Chelating Lewis Acid. Chem. Sci. 13, 2022, 2378-2384

Despite the fact that intramolecular crossed [2+2] photocycloaddition reactions lead to intriguing, otherwise inaccessible bridged skeletons, there has so far not been any enantioselective variants thereof. This study concerned the enantioselective crossed [2+2]-photocycloaddition of 2-(alkenyl¬oxy)cyclohex-2-enones to bridged cyclobutanes. It was found that the reaction could be performed with high enantioselectivity (80-94% ee) when employing a chiral-at-rhodium Lewis acid catalyst (2 mol%) under visible light irradiation. The oxygen atom contained in the tether allowed a bidentate binding of the substrate by a chiral Lewis acid which enabled a stereocontrolled intramolecular [2+2] photocycloaddition to tricyclic bridged products that contain up to four stereogenic centres and a tertiary oxygen substituted carbon atom in α-position to the carbonyl group. The synthetic utility of the method was demonstrated by different consecutive reactions that allowed the manipulation of the crossed cyclobutane scaffold preserving the enantiopurity of the compounds.                                                                                                                                                                           

More Publications

Gilbert, Audrey; Bach, Thorsten: The Awakening of a Sleeping Beauty: The ortho Photocycloaddition in the Total Synthesis of Protoilludane- and Prezizaene-Type ­Sesquiterpenes. Synlett, 34, 2023, 1343-1355

Photochemical cascade (domino) reactions provide a unique opportunity for the construction of complex molecular architectures. Specifically, an intramolecular ortho photocycloaddition of 7-(alkenyloxy)-indanones triggers a sequence of consecutive reactions that can lead in a single operation to the complete skeleton of two important classes of sesquiterpenes: protoilludanes and prezizaenes. In the former case, two transformations follow the initial photocycloaddition, while in the latter case, there are three consecutive transformations, two of which are initiated by a photon. Remarkably, the reaction cascades proceed with exquisite diastereoselectivity, generating three (protoilludane) or five (prezizaene) stereogenic centers with defined relative configurations.

Sempere, Yeshua; Morgenstern, Martin; Bach, Thorsten; Plaza, Manuel: Reactivity and Selectivity Modulation Within a Molecular Assembly: Recent Examples from Photochemistry. Photochem. Photobiol. Sci. 21, 2022, 719–737

In recent years, photochemical reactions have emerged as powerful transformations which significantly expand the repertoire of organic synthesis. Nevertheless, a certain lack of selectivity can sometimes limit their application and scope. In this context, nowadays a major research effort continues to focus on an improved control over stereo- and chemoselectivity that can be achieved in molecular assemblies between photosubstrates and an appropriate host molecule. In this tutorial review, some recent and representative examples of photochemical transformations were collected whose unique outcome is dictated by the formation of a molecular assembly driven by non-covalent weak interactions. 

Engl, Sebastian; Reiser, Oliver: Copper-photocatalyzed ATRA reactions: concepts, applications, and opportunities, Chem. Soc. Rev. 51, 2022, 5287-5299

Atom transfer radical addition (ATRA) reactions are linchpin transformations in synthetic chemistry enabling the atom-economic difunctionalization of alkenes. Thereby a rich chemical space can be accessed through smart combinations of simple starting materials. Originally, these reactions required toxic and hazardous radical initiators or harsh thermal activation and thus, the recent resurgence and dramatic evolution of photocatalysis appeared as an attractive complement to catalyze such transformations in a mild and energy-efficient manner. Initially, this technique relied primarily on complexes of precious metals, such as ruthenium or iridium, to absorb the visible light. Hence, copper photocatalysis rapidly developed into a powerful alternative, not just from an economic point of view. Originally considered to be disadvantageous as a pathway for deactivation by quenching their excited state, the dynamic nature of Cu-complexes enables them to undergo facile ligand exchange and thus opens up special opportunities for transformations utilizing their inner-coordination sphere. Moreover, the ability of Cu(II), representing a persistent radical, to capture incipient radicals offers the possibility to access heretofore elusive two-component, but also three-component, ATRA reactions, not feasible with ruthenium or iridium catalysts. In this regard, the idea of using Cu(I)-substrate assemblies as active photocatalysts is an emerging field to achieve such 3-component coupling reactions even under enantioselective control, which is reflected by an increasing number of reports being covered in this review.

2021

Publications

Großkopf, Johannes; Plaza, Manuel; Seitz, Antonia; Breitenlechner, Stefan; Storch, Golo, Bach, Thorsten: Photochemical Deracemization at sp3-hybridized Carbon Centers via a Reversible Hydrogen Atom Transfer. J. Am Chem. Soc. 143 (50), 2021, 21241-21245

The selective synthesis of enantiopure compounds has received great attention and became a flourishing research area within recent decades. Despite a tremendous progress in this field, it remains challenging to convert a racemic mixture directly into one of its enantiomers. In this work a conceptually new method for a photochemical deracemization, apart from triplet sensitization or photoredox processes, was established which relies on a selective hydrogen atom transfer (HAT) to a chiral benzophenone photocatalyst. It enables the conversion of racemic hydantoins into a single enantiomer (ee’s of up to 99%) by reverting the configuration at a sp3-hybridized carbon center.                                                                                                                                                                                  

Till, Marion; Streitferdt, Verena; Scott, Daniel J.; Mende, Michael; Gschwind, Ruth M.; Wolf, Robert: Photochemical transformation of chlorobenzenes and white phosphorus into arylphospines and phosphounium salts. Chem. Commun. 58, 2021, 1100-1103

Chlorobenzenes are important starting materials for the preparation of commercially valuable triarylphosphines and tetraarylphosphonium salts, but their use for the direct arylation of elemental phosphorus has been elusive. Here we describe a simple photochemical route toward such products. UV-LED irradiation (365 nm) of chlorobenzenes, white phosphorus (P4) and the organic superphotoreductant tetrakis(dimethylamino)ethylene (TDAE) affords the desired arylphosphorus compounds in a single reaction step.

Keil, Erika; Malevich, Pavel; Hauer, Jürgen: Achromatic frequency doubling of supercontinuum pulses for transient absorption spectroscopy. Optics Express 29, 2021, 39042-39054

In this article, a technique for obtaining tunable ultrashort pulses in the near UV and blue spectral range is described. The resulting pulses are broadband and tunable, have stable pulse energies and can be compressed down to 12 fs by conventional optics. The suitability of the pulses for spectroscopic applications is tested by employing them as a pump in a transient absorption experiment on β-carotene in solution.

Rothfelder, Robin; Streitferdt, Verena; Lennert, Ulrich; Cammarata, Jose; Scott, Daniel J.; Zeitler, Kirsten; Gschwind, Ruth M.; Wolf, Robert: Photocatalytic Arylation of P4 and PH3: Reaction Development Through Mechanistic Insight. Angew. Chem. Int. Ed. 60, 2021, 24650-24658

Detailed 31P{1H} NMR spectroscopic investigations provide deeper insight into the complex, multi-step mechanisms involved in the recently reported photocatalytic arylation of white phosphorus (P4). Specifically, these studies have identified a number of previously unrecognized side products, which arise from an unexpected non-innocent behavior of the commonly employed terminal reductant Et3N. The different rate of formation of these products explains discrepancies in the performance of the two most effective catalysts, [Ir(dtbbpy)(ppy)2][PF6] (dtbbpy=4,4′-di-tert-butyl-2,2′-bipyridine) and 3DPAFIPN. Inspired by the observation of PH3 as a minor intermediate, we have developed the first catalytic procedure for the arylation of this key industrial compound. Similar to P4 arylation, this method affords valuable triarylphosphines or tetraarylphosphonium salts depending on the steric profile of the aryl substituents.

Krolo, Tomislav; Bhattacharyya, Aditya; Reiser, Oliver: Accessing HIV-1 Protease Inhibitors through Visible-Light-Mediated Sequential Photocatalytic Decarboxylative Radical Conjugate Addition–Elimination–Oxa-Michael Reactions. Org. Lett. 23, 2021, 6283-6287

A photocatalytic decarboxylative radical conjugate addition–elimination–oxa-Michael reaction of hydroxyalkylated carboxylic acids with cyclopentenones is developed to construct diverse cyclopentanonyl-fused functionalized 5–7 membered cyclic ethers. The stereoselective synthetic strategy is amenable to substructural variation, establishing a direct total synthetic route to two diastereomers of C3-amino cyclopentyltetrahydrofuranyl-derived potent HIV-1 protease inhibitors with low nanomolar IC50 values.