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.
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.
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.
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.
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.
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.