Project Area B

Lewis/Brønsted acid-base interactions, ionic interactions and hydrogen bonds

 

The projects in this section are thematically connected by a defined, weak interaction within an assembly, like the interaction of Lewis acids and Brønsted acids, ionic interaction and hydrogen bonds.

© by Chair of Organic
Chemistry I/TUM

B1: Chromophore Activation by Lewis Acid Coordination

Introduction. Recent interest in Lewis acid catalyzed photochemical reactions has been triggered by the desire to devise enantioselective methods for the construction of typical photochemical reaction products, e.g. cyclobutanes. The existing methods can be crudely classified into four categories based on their mode of action:

(a) The Lewis acid changes the dynamic properties of the excited state(s) by opening a reaction channel that is not accessible in the absence of the Lewis acid (IC = internal conversion, ISC = intersystem crossing).

(b) The Lewis acid alters the energy of the singlet excited state(s), which is typically detected by a bathochromic (or hypsochromic) shift in the UV/Vis spectrum (S0 = electronic ground state, S1 = first excited singlet state).

(c) The Lewis acid modulates the energy of the triplet excited state(s), which is detectable in the phosphorescence spectrum or by quenching studies with a triplet sensitizer the triplet state energy of which is known (T1 = lowest triplet state).

(d) By changing the energy of the excited state, the Lewis acid invariably leads to a change in the redox potential of the excited state making it a stronger oxidant or reductant. If the triplet state is populated, it will be the redox properties of T1 which are altered.

 

Summary of the Project. The main goal of the project is to explore how Lewis acids modulate the photophysical properties of a given chromophore in an assembly and how this modulation can be exploited for unprecedented selective photochemical reactions. A strategic input is expected from collaborations with theoretical chemistry and spectroscopy by which the excited state properties of the Lewis acid complexes are interrogated. The project aims to discover and to explore salient features of complexes between typical chromophores and Lewis acids. Specifically, carbonyl compounds (aldehydes, ketones, carboxylates), sulfones, and arenes will be studied. Synthetically, the goal is to allow for a selective excitation of a Lewis acid-substrate complex which in turn can be employed to perform catalytic enantioselective, site-selective and type-selective transformations, ideally by visible-light irradiation. It is planned to employ a,b-unsaturated carbonyl compounds (enones) in photochemical reactions which extend beyond [2+2] photocycloaddition chemistry. Relevant reactions – some of which are expected to occur on the singlet hypersurface – include 1,3-migration, E/Z-isomerization followed by subsequent addition, hydrogen abstraction, and photocyclization. In arene photochemistry, the focus will be on reactions that allow for C-C bond formation at the arene core and for a dearomatization of the benzene ring. New binding motifs for Lewis acid coordination are proposed and will be tested in exploratory experiments.

Publications

Current Publications 

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 ⇒ See Publication

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 ⇒ See Publication

Key Publications

Peschel, Martin; Kabacinski, Piotr; Schwinger, Daniel P; Thyrhaug, Erling; Cerullo, Giulio; Bach, Thorsten; Hauer, Jürgen; de Vivie-Riedle, Regina: Activation of 2‐Cyclohexenone by BF3 Coordination: Mechanistic Insights from Theory and Experiment. Angew. Chem. Int. Ed. 60, 2021, 10155-10163

Schwinger, Daniel P.; Bach, Thorsten: Chiral 1,3,2-Oxazaborolidine Catalysts for Enantioselective Photochemical Reactions. Acc. Chem. Res. 53 (9), 2020, 1933-1943

Leverenz, Malte; Merten, Christian; Dreuw, Andreas; Bach, Thorsten: Lewis Acid Catalyzed Enantioselective Photochemical Rearrangements on the Singlet Potential Energy Surface. J. Am. Chem. Soc. 141, 2019, 20053-20057

Stegbauer, Simone; Jeremias, Noah; Jandl, Christian; Bach, Thorsten: Reversal of reaction type selectivity by Lewis acid coordination: the ortho photocycloaddition of 1- and 2-naphthaldehyde. Chem. Sci. 10, 2019, 8566-8570

Poplata, Saner; Bauer, Andreas; Storch, Golo; Bach, Thorsten: Intramolecular [2+2] Photocycloaddition of Cyclic Enones: Selectivity Control by Lewis Acids and Mechanistic Implications. Chem. Eur. J. 25, 2019, 8135–8148

 

Organic Chemistry, Synthesis

Prof. Dr. Thorsten Bach                                                                       

B2: Hydrogen Bonds and Ion Pairs in Enantioselective Photochemistry

Introduction The field of enantioselective photochemistry has rapidly grown in recent years and many contributions deal with reactions in which a hydrogen bonding or ion pairing interaction is involved. The distinction whether a hydrogen bond or an ion pair is operative is not always trivial and the classification shown below is somewhat arbitrary. Brønsted acids act via a hydrogen-bonded ion pair, but charge separation has frequently been observed. In the current project we rely mainly on two non-covalent motifs that operate to form a given assembly, (1) a two-point hydrogen bond interaction between chiral lactams and a given substrate, and (2) the protonation of a substrate with a chiral Brønsted acid leading to a hydrogen-bonded or a strict ion pair. In both scenarios the species that undergoes an enantioselective transformation is in its excited singlet or triplet state, which is an important distinction to most reactions reported so far.

Summary of the Project. The project aims to employ hydrogen bonding and ion pairing interactions in enantioselective photochemical reactions. The focus is on the generation of excited species within a substrate-catalyst assembly as opposed to the formation of radical intermediates by photoredox processes. The goal is approached (a) by the use of chiral lactams or phosphoric acids which display an internal, light-collecting sensitizing unit to transfer energy exclusively to a bound substrate and (b) by devising substrates which are photochemically transparent but are activated towards excitation by a chiral Brønsted acid. In the former scenario, emphasis is placed on catalytic deracemization reactions in their purest sense converting a racemic mixture into a single enantiomer by sensitization. Suitable catalysts for this transformation are based on the 1,5,7-trimethyl-3-azabicyclo[3.3.1]nonan-2-one skeleton and new substrate classes will be explored. Mechanistic insights are expected from transient absorption spectroscopy experiments and from titration studies. The work with chiral acids will rely largely on the binding motif of carboxylic acids and imines to these acids. Both motifs can be interrogated by NMR spectroscopic techniques and the assemblies can be studied prior to, and possibly also during excitation. In terms of scope, the exclusive focus will be on reactions that are unique to photochemistry and cannot be achieved thermally. The repertoire thus includes [2+2] photocycloaddition, photochemical rearrangement, and photocyclization reactions of synthetically relevant substrate classes, which have so far remained unexplored.

Publications

Current 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 ⇒ See Publication

 

Key Publications

Li, Xinyao; Kutta, Roger J.; Jandl, Christian; Bauer, Andreas; Nuernberger, Patrick; Bach, Thorsten: Photochemically Induced Ring Opening of Spirocyclopropyl Oxindoles: Evidence for a Triplet 1,3‐Diradical Intermediate and Deracemization by a Chiral Sensitizer. Angew. Chem. Int. Ed. 59, 2020, 21640-21647 

Hörmann, Fabian M.; Kerzig, Christoph; Chung, Tim S.; Bauer, Andreas; Wenger, Oliver S.; Bach, Thorsten: Triplet Energy Transfer from Ruthenium Complexes to Chiral Eniminium Ions: Enantioselective Synthesis of Cyclobutane­carbaldehydes by [2+2] Photocycloaddition. Angew. Chem. Int. Ed. 59 (24), 2020, 9659-9668 

Pecho, Franziska; Zou, You-Quan; Gramüller, Johannes; Mori, Tadashi; Huber, Stefan M.; Bauer, Andreas; Gschwind, Ruth M.; Bach, Thorsten: A Thioxanthone Sensitizer with a Chiral Phosphoric Acid Binding Site: Properties and Applications in Visible Light‐Mediated Cycloadditions. Chem. Eur. J. 26, 2020, 5190-5194

Wimberger, Laura; Kratz, Thilo; Bach, Thorsten: Photochemical Deracemization of Chiral Sulfoxides Catalyzed by a Hydrogen-Bonding Xanthone Sensitizer. Synthesis 51, 2019, 4417-4424 

Hölzl-Hobmeier, Alena; Bauer, Andreas; Vieira Silva, Alexandre; Huber, Stefan M.; Bannwarth, Christoph; Bach, Thorsten: Catalytic deracemization of chiral allenes by sensitized excitation with visible light. Nature 564, 2018, 240-243

 

Organic Chemistry, Synthesis

Prof. Dr. Thorsten Bach

B3: NMR Spectroscopic Tools to Detect Brønsted/Lewis Acid-Base Preorganization in Photocatalysis

The main goal of the project is to detect, rationalize and design the effect of H-bonds and Lewis-acid/base interactions in photocatalysis. Advanced NMR-spectroscopic methods in combination with selected and designed model systems from synthetic collaboration partners will be used to address the impact of isolated H-bonds, cooperativity effects and extended H-bond networks in photocatalysis. In addition, for the by far more flexible and less directed Lewis acid base interactions NMR spectroscopic tools shall be tested to develop an access to structure-based Lewis acid base effects in photocatalysis.

Organic Chemistry, Spectroscopy

Prof. Dr. Ruth M. Gschwind

B4: A Photoredox/Lewis-Acid Hybrid Catalyst Design for the Covalent Activation of Alkenes

The prime goal of this project is to rationally design photoredox-Lewis-acid hybrid catalysts for the electrophilic activation of electronically unbiased alkenes enabled by visible-light-induced dynamic covalent substrate-catalyst-assemblies. To realize this objective, an in-depth understanding of the (photo)physical and mechanistic features of such a hybrid catalysis regime is indispensable. Thus, strategic expertise from collaborations in the areas of spectroscopy and computational chemistry is envisioned to culminate in the minute analysis of key factors that govern the activation of the hybrid catalysts and their interactions with the substrates prior, during, and after the photoexcitation event.

Organic Chemistry, Synthesis

Prof. Dr. Alexander Breder

B5: Tuning Radical Reactivity in Photocatalytic Transformations of NHC-Activated Substrates

The project B5 aims to harness the unique ability of N-heterocyclic carbenes (NHCs) to stabilize adjacent radical centers (carbon, oxygen: part A; boron: part B) for synthetic applications i.a. cyclisation cascades). The visible light induced formation of the radical centers will take place only after successful assembly of the according NHC-substrate adducts and their reactivity will be modulated by secondary interactions in the binary or ternary complexes. Supporting in-depth mechanistic investigations will make use of time-resolved spectroscopy on various time-scales and sophisticated computations (MDs, electronic structure calculations).

Physical Organic and Computational Chemistry

Prof. Dr. Julia Rehbein

B6: Base-Promoted Oxidative PCET Remote Functionalization

The project aims at the improved understanding of the association of base, OH-substrate and photocatalytic oxidant in (oxidative) multisite proton-coupled electron transfer reactions (MS PCET). The identification of the critical interactions within these ternary assemblies, which is sought after in collaboration with spectroscopy, and the modulation of these assembly effects to facilitate PCET should allow for alkoxy radical generation under preferably mild conditions. From a synthetic point of view this in turn should enable versatile photocatalytic remote functionalization of non-activated alcohols, especially with respect to compatibility with multicatalytic settings.

Organic Chemistry, Synthesis

Prof. Dr. Kirsten Zeitler

B7: Photoexcitation of Reduced, Molecular Flavins and their Application in Catalysis

This research programme focusses on the design and application of molecular, reduced flavin catalysts as one-electron donors in organic transformations upon excitation with light. Defined catalyst-substrate interactions are expected to be crucial for achieving efficient reactivity despite of short excited state lifetimes. This assembly formation is also the key for achieving positional and stereoselectivity in the proposed catalytic reactions. Carbon-carbon bond formation after initial one-electron reduction of substrates is the common theme of all outlined transformations and the products display valuable structural motifs in organic synthesis.

Current Publications

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 ⇒ See Publication

Organic Chemistry, Synthesis

Dr. Golo Storch

B8: Transient Absorption on Multiple Time Scales - from Internal Conversion to Charge Transfer Processes

Figure: timescales of interest for a photocatalytic reaction (top row). Schemes for transient absorption (Workpackage or WP 1) and impulsive vibrational spectroscopy on the fly (WP 2).

Reaction dynamics along a photocatalytic cycle occur on a broad range of timescales, spanning ten orders of magnitude; from hundreds of femtoseconds (fs) for internal conversion in the photocatalyst to millisecond lifetimes of charge separated species in solution. The major goal of this project is to devise, construct and apply transient absorption (TA) experiments covering the entire dynamic range of photocatalytic reactions. We will upgrade an existing setup for fs TA and exploit the sub 15 fs time resolution for impulsive vibrational spectroscopy of photocatalysts, in an effort to determine the vibrational modes driving the internal conversion events towards reactive states. Ultrafast deactivation dynamics – from fs to ns – will be probed after UV and visible excitation in Lewis acid complexes, photoredox catalysts, flavin derivatives and several catalyst-substrate complexes. To widen the scan range to hundreds of μs, we will construct a multiscale TA experiment, combining a tunable ns excitation source and fs whitelight for probing. This will allow us to observe an entire photocatalytic cycle on all its inherent timescales. We will improve the selectivity and information content as compared to conventional TA by the development of new spectroscopic methods: ns actinic pump – fs re-pump – fs probe and ns actinic pump – fs impulsive vibrational spectroscopy.

Current Publications

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

Physical Chemistry, Spectroscopy

Prof. Dr. Jürgen Hauer

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