Publications



2022


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.


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.


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.


Proessdorf, Johanna; Jandl, Christian; Pickl, Thomas; Bach, Thorsten: Arene Activation through Iminium Ions: Product Diversity from Intramolecular Photocycloaddition Reactions, Angew. Chem. Int. Ed. 61, 2022, e202208329

While 2-alk-ω-enyloxy-sustituted benzaldehydes do not display any photochemical reactivity at the arene core, the respective iminium perchlorates were found to undergo efficient reactions either upon direct irradiation (λ = 366 nm) or under sensitizing conditions (λ = 420 nm, 2.5 mol% thioxanthen-9-one). Three pathways were found: (a) Most commonly, the reaction led to benzoxacyclic products in which the olefin in the tether underwent a formal, yet unprecedented carboformylation (13 examples, 44-99% yield). The cascade process occurred with high diastereoselectivity and was found to be stereoconvergent. (b) If a substituent resides in the 3-position of the benzene ring, a meta photocyclo­addition was observed which produced tetracyclic skeletons with five stereogenic centers in excellent regio- and diastereoselectivity (2 examples, 58-79% yield). (c) If the tether was internally substituted at the alkene, an arene photocycloaddition was avoided and an azetidine was formed in an aza Paternò-Büchi reaction (2 examples, 95-98% yield).


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.


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.


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


More Publications

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., 2022, 13, 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.                                                                                                                                                                           

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


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.