Tetrahydronaphthalene-2-yl acrylates are shown to undergo efficient ketyl radical cyclization-lactonization reactions leading to structurally elaborate tetrahydronaphthocyclopropa[1,2-b]furanones. The reductive ketyl radical cyclizations can be induced photocatalytically under mild and acid-free conditions in an amine/water buffer system as well as electrosynthetically, and the polycyclic strained γ-lactone products are generated with high stereoselectivity and yields.

Tetrahydronaphthalene-2-yl acrylates are shown to undergo efficient ketyl radical cyclization-lactonization reactions leading to structurally elaborate tetrahydronaphthocyclopropa[1,2-b]furanones. The reductive ketyl radical cyclizations can be induced photocatalytically under mild and acid-free conditions in an amine/water buffer system as well as electrosynthetically, and the polycyclic strained gamma-lactone products are generated with high stereoselectivity and yields.

1,8-Diazabicyclo(5.4.0)undec-7-ene catalyzes the deconjugative alpha-alkylation of 2-butylidene 1-indanone and 1-tetralone with electrophilic alkenes, to give alpha,alpha-disubstituted beta,gamma-unsaturated indanone and tetralone products, under mild conditions, and in moderate to excellent yields. Further elaboration of the 1-indanone and 1-tetralone-derived skipped enones gave delta,epsilon-unsaturated alkenoic acids, which underwent diastereoselective iodo- and epoxylactonizations, furnishing valuable [4.5]- and [5.5]-spirocyclic delta-lactones in high yields.

A urea-based pristine polymeric carbon nitride catalyzes the aerobic epoxidation of citronellol under visible light irradiation with low-power blue LEDs. Formation of 6,7-epoxycitronellol in this reaction is remarkably selective yet relatively slow requiring 72 h of continuous irradiation. The aerobic photocatalyzed epoxidation is readily accelerated with isobutyraldehyde as a comediator, and a general photocatalytic procedure for the epoxidation of terpenoid substrates as well as styrene derivatives is thus developed to give the corresponding epoxides in good yields within attractive reaction times. The carbon nitride-photocatalyzed aerobic epoxidation is demonstrated in 14 examples, and the epoxidation of citronellol enables a short and sustainable three-step synthesis of the industrially relevant terpenoid fragrance compound rose oxide.

A set of five polymeric carbon nitrides (pCNs) made from diverse low-molecular precursors was compared with metal chalcogenide and pnictogenide semiconductors for their effectiveness in visible light-induced organic radical reactions. The productivity of the heterogenous photocatalysts in the decarboxylative Giese addition of N-phenylglycine with cyclopentenone was studied at different irradiation wavelengths ranging from 380 to 450 nm, as well as in the deaminative radical donor-acceptor-donor (DAD) three-component coupling of N-benzyl pyridinium salts with N-methylmaleimide and 1,1-diarylethylenes. The heterogenous photocatalytic radical three-component reactions were achieved in high diastereoselectivities and with high yields if the electronic and steric properties of the reactants were matched with the appropriate heterogeneous photocatalyst.

The C10a-acetoxylated tetrahydroazepino[1,2-a]indole-6,11-diones are a class of tricyclic oxindoles that feature an alpha-keto-N,O-acetal substructure, rendering them highly susceptible to SET reduction followed by fragmentation. In protic medium, they undergo a PCET-assisted two-step reduction including an interposed C-O bond cleavage that can be initiated photocatalytically as well as by cathodic reduction, and which generates nucleophilic ketyl radicals. In the presence of acrylonitrile and DIPEA as additional reactants, the photoinduced reaction unfolds as a tandem C-O bond reduction/ketyl radical conjugate addition, to furnish C10a-reduced, C11-cyanoethyl-substituted tricyclic azepino-[1,2-a]indole derivatives with high stereoselectivity.

C10a-Acetoxylated perhydroazepino[1,2-a]-indoles, accessible via visible light-mediated sensitized photooxygenation of cyclo-hepta[b]indoles, are precursors to structurally elaborate carbon-centered radicals. Their photoredox-catalyzed SET reduction by phenothiazine or phenoxazine photocatalysts, followed by fragmentation and C-O bond cleavage, liberates tricyclic alpha-amino-alpha-carbonyl radicals that readily engage in radical addition reactions with silyl enol ethers and silyl ketene acetals. The C-C functionalized azepinoindole[1,2-a]indoles are useful building blocks for the synthesis of polycyclic indole derivatives as shown by the controlled borohydride reduction of a C10a-methylenecarboxylate derivative, which leads stereoselectively to tetracyclic azepino[1,2-a]furo[3,2-b]indoles. The photocatalytic method developed herein is also suitable for the radical functionalization of simple alpha-acetoxy acetophenones.

Dihydroazepino[1,2-a]indole diones are tricyclic N-acyl-2-alkylidene-3-oxindole enones that readily engage in tertiary phosphine-catalyzed intermolecular coupling reactions with acceptor-substituted alkenes. In these reactions, the tricyclic α-substituted enones undergo an α-alkylation with concomitant formation of a quaternary stereocenter, as well as the installation of a new double bond within the seven-membered azepane ring. The organocatalytic reaction constitutes a special case of the crossed intermolecular Rauhut-Currier reaction as the presence of the α-substituent in the enones prohibits the formation of an α,β-unsaturated product, but instead, skipped β,γ-unsaturated enones are obtained. With allene carboxylates as alternative coupling partners, the crossed Rauhut-Currier-type reaction competes with a regioselective allene to enone [3 + 2]-cycloaddition, and the product selectivity can be controlled by the choice of the phosphine organocatalyst.

The dihydroazepino[1,2-a]indole diones 3 are tricyclic oxindole-type enones which are readily accessible by catalytic photooxygenation of cyclohepta[b]indoles 1 followed by dehydration. Lewis acid-catalysed oxa Diels-Alder reactions of enones 3 with enol ethers 4 were developed that lead to novel tetracyclic azepane-fused pyrano[3,2-b]indoles 5, with high stereoselectivity and under mild reaction conditions.

2-Cyanochromone (1) readily undergoes visible light-induced photocycloadditions with diverse alkene partners mediated by (Ir[dF(CF3)ppy]2(dtbpy))PF6 as the photosensitizer. While mono-, di- and trisubstituted styrenes and acrylonitriles as the reactants lead to [2 + 2] cycloadducts with good regiocontrol and high diastereoselectivity, the use of trialkyl-substituted alkenes allows for the isolation of cyclopentenone-fused chromones resulting from a [3 + 2] cycloaddition process in moderate yields.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

A short total synthesis of the Kopsia alkaloid (±)-mersicarpine is presented. As the key step, a visible light-induced catalytic cascade photooxygenation was utilized, to convert a 3,3-disubstituted tetrahydrocarbazole intermediate, in one step, into a perhydropyrido[1,2-a]indole dione as the immediate precursor to the natural product. The synthesis of mersicarpine was achieved with an overall yield of 12% over 13 steps.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Photocatalytic dehydrogenative [2 + 2] cycloadditions between amines and alkenes were developed that allow for the stereoselective and high-yielding synthesis of functionalized azetidines. The oxidative formal Aza Paternò-Büchi reactions are induced by photoredox-catalyzed aerobic oxidation of dihydroquinoxalinones 1 as the amines, and in the presence of structurally diverse alkenes 3 intermolecular [2 + 2] cyclization to dihydro-1H-azeto[1,2-a]quinoxalin-3(4H)-ones 4 occurs. The utility of the method is illustrated by the selective conversion of amino acid derived dihydroquinoxalinones 1, including oxidation-prone lysine and tryptophan derivatives.

Spirooxindole-1,3-oxazines are a small and structurally unique class of spirooxindole alkaloids. To date, only four of these compounds have been isolated from natural sources, and their biological properties remained unknown thus far. Dioxyreserpine is a synthetic spirooxindole-1,3-oxazine, that can readily be prepared from the Rauvolfia alkaloid (-)-reserpine by catalytic photooxygenation. While dioxyreserpine itself was now identified as a moderately effective antitumoral agent, structurally modified analogs of it emerged as a new class of highly potent and selective growth inhibitors of various human cancers, including pancreatic cancers. Systematic structural optimization ultimately led to an inhibitor displaying low-micromolar IC50-values against six cancer cell lines as well as selective apoptosis induction in vitro.

N-Benzyl- and N-2 degrees-alkylpyridinium salts were engaged in visible-light-driven, photoredox-induced radical-cationic three-component couplings with N-methylmaleimide and acrylonitrile as radical acceptors, in combination with 1,1-diarylethylenes as donor alkenes. These multicomponent coupling reactions could be achieved under mild conditions, with high efficiency, and to furnish diverse 3,4-disubstituted pyrrolidin-2,5-dione products with high stereoselectivity. In addition, 2,3-diaryl-1,3-butadienes could be utilized as alternative donor alkene components, to furnish diastereomerically pure 1,2,3-trisubstituted 1,3-butadienes as the coupling products.

The Cover Feature shows a radical three-component coupling driven by visible light photoredox catalysis. Single electron transfer (SET) reduction of N-alkylpyridinium salts liberates nucleophilic carbon radicals that successively couple with an acceptor and a donor alkene, enabling a stereoselective synthesis of new succinimide derivatives. Cover image made by Marcin Henk Kowalski. More information can be found in the Communication by Malte Brasholz and co-workers.

AbstractElektrochemische Synthese – Naturstoffe und deren Synthese – photokatalytische Redoxchemie – Farbstoffe – Nanostrukturen – Wirkstoffe – asymmetrische Katalyse und mehr.