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.

Project Area A

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.

Project Area C

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.

Project Area B

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).

Project Area C

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.

Cyclohept-1-ene-1-carbaldehyde undergoes photoinduced E → Z 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%).

Project Area B

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.

Project Area C

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.

Project Area A

Cross-coupling reactions are among the most important transformations in modern organic synthesis^1,2,3. 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.

Project Area C

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.

Project Area B

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).

Project Area B

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.

Project Area A

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.

Project Area B

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.

Project Area B

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.

Project Area B

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

Project Area A

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.

Project Area B

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.

Project Area C

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).

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.

Project Area C

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.

Project Area C

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.

Project Area A

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.

Project Area C

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.

Project Area A

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.

Project Area A & B

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 BiCl₅^2– 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.

Project Area A