Visible Light-Induced Oxy-perfluoroalkylation of Olefins via Ternary Electron Donor-Acceptor Complexes.

Perfluoroalkyl iodides generally formed electron donor-acceptor (EDA) complexes by halogen bonding with a nitrogen atom containing Lewis bases. Since the electronegativity of the oxygen atom is stronger than that of the nitrogen atom, the resulting Rf-I···O-type halogen bonding EDA complex is less inclined to undergo electron transfer. Here, we reported rare ternary EDA complexes among perfluoroalkyl iodide, oxygen atom, and base. Mechanism experiments and density functional theory theoretical (DFT) calculations indicated that a base-promoted proton-coupled electron transfer (PCET) process was involved in this photochemical reaction. The intracomplex electron transfer event generated two radical species, perfluoroalkyl radical and TEMPO radical, enabling the subsequent oxy-perfluoroalkylation of olefins.

Nickel/photoredox dual catalyzed arylalkylation of nonactivated alkenes.

Alkene dicarbofunctionalization is an efficient strategy and operation-economic fashion for introducing complexity in molecules. A nickel/photoredox dual catalyzed arylalkylation of nonactivated alkenes for the simultaneous construction of one C(sp3)-C(sp3) bond and one C(sp3)-C(sp2) bond has been developed. The mild catalytic method provided valuable indanethylamine derivatives with wide substrate scope and good functional group compatibility. An enantioselective dicarbofunctionalization was also achieved with pyridine-oxazoline as a ligand. The efficiency of metallaphotoredox dicarbofunctionalization was demonstrated for the concise synthesis of pharmaceutically active compounds.

Discovery of potential novel TRPC5 inhibitors by virtual screening and bioassay.

The transient receptor potential canonical channel 5 (TRPC5), a member of the TRPC family, plays a crucial role in the regulation of various physiological activities and diseases, including those related to the central nervous system, cardiovascular system, kidney, and cancer. As a nonselective cation channel, TRPC5 mainly controls the influx of extracellular Ca2+ into cells, thereby modulating cellular depolarization and intracellular ion concentration. Inhibition of TRPC5 by small molecules presents a promising approach for the treatment of TRPC5-associated diseases. In this study, we conducted a comprehensive virtual screening of more than 1.5 million molecules from the Chemdiv database (https://www.chemdiv.com) to identify potential inhibitors of hTRPC5, utilizing the published structures and binding sites of hTRPC5 as a basis. Lipinski's rule, Veber's rule, PAINS filters, pharmacophore analysis, molecular docking, ADMET evaluation and cluster analysis methods were applied for the screening. From this rigorous screening process, 18 candidates exhibiting higher affinities to hTRPC5 were subsequently evaluated for their inhibitory effects on Ca2+ influx using a fluorescence-based assay. Notably, two molecules, namely SML-1 and SML-13, demonstrated significant inhibition of intracellular Ca2+ levels in hTRPC5-overexpressing HEK 293T cells, with IC50 values of 10.2 µM and 10.3 µM, respectively. These findings highlight SML-1 and SML-13 as potential lead molecules for the development of therapeutics targeting hTRPC5 and its associated physiological activities and diseases.

Redox-Neutral Intramolecular Dearomative Spirocyclization of Phenols Induced by Visible Light.

Described herein is a redox-neutral intramolecular dearomative spirocyclization induced by visible light. The photochemical cyclization was catalyzed by a phenolate anion-derived photocatalyst and delivered the spirocyclohexadienone. Mechanistic experiments revealed that the aryl halide was reduced to aryl radical via the single-electron transfer (SET) process under visible light irradiation. The electrophilic addition of an aryl radical with the phenolate anion moiety gave a radical anion intermediate, which recycled the photocatalyst by a second SET process.

Water-mediated radical C-H tosylation of alkenes with tosyl cyanide.

The water-mediated tosylation of alkenes with tosyl cyanide was discovered. Experimental investigations revealed that the reaction was initiated by the in situ formation of sulfinyl sulfone in the presence of water. The sulfinyl sulfone species decomposed to a sulfonyl radical and a sulfinyl radical through homolytic fission. The vinyl sulfone was afforded via sequential addition of the alkene to the sulfonyl radical and the sulfinyl radical, followed by ß-elimination of a sulfinyl moiety.

Synthesis of C2-Carbonyl Indoles via Visible Light-Induced Oxidative Cleavage of an Aminomethylene Group.

A strategy for photochemical oxidative cleavage of the aminomethylene group at the C2 position of indole was developed to synthesize C2-carbonyl indoles. The reaction was initiated by the photochemical oxidation of N1, followed by a water-assisted concerted H-shift by abstracting hydrogen from aminomethylene. Bromopyridine was discovered to play dual roles as an oxidant for the regeneration of photocatalysts and as an accelerant for the single-electron transfer process.

Direct synthesis of C3-alkynyl pyrroloindolines from tryptamines via a visible-light-induced radical cascade reaction.

A visible-light-induced radical cascade reaction for the direct alkynylation of tryptamines with alkynyl sulfones was developed, affording a series of C3-alkynyl pyrroloindolines in excellent yields. This method features readily available substrates, good functional group tolerability, and scalability. C3-alkynyl pyrroloindolines show great potential as useful building blocks in the preparation of complex and valuable pyrroloindoline alkaloids.

Decatungstate Catalyzed Photochemical Acetylation of C(sp3)-H Bonds.

A direct acetylation of inert C(sp3)-H bonds was developed that was catalyzed by decatungstate under visible light irradiation and was followed by radical addition-disassociation with phenylsulfonyl ethanone oxime. The reaction displays site-selectivity in multiple C(sp3)-H bonds without prefunctionalization and directing groups. Various functional groups are well-tolerated and natural molecules are structurally feasible. CF3-modified phenylsulfonyl ethanone oxime was discovered to be necessary for enhancing the electrophilicity of imine and lowering the C-S bond cleavage energy.

Photochemical Synthesis of Indolocarbazoles through Tandem Indolization/Dimerization/Mannich Cyclization from Allenes.

Indolocarbazole alkaloids and their derivatives were discovered to have potent protein kinase and topoisomerase I inhibitory activities. Disclosed herein is the photochemical synthesis of the indolocarbazole ring system from N-allenyl-2-iodoanilines. The tandem protocol included visible-light-mediated 5-exo-trig radical cyclization and subsequent radical dimerization, followed by acid-promoted deprotection and intramolecular Mannich cyclization. This strategy showed exceptional functional group tolerance and was successfully applied in the concise synthesis of natural products tjipanazoles B and D.

Strategies for total synthesis of bispyrrolidinoindoline alkaloids.

Covering up to 2021Complex cyclotryptamine alkaloids with a bispyrrolidino[2,3-b]indoline (BPI) skeleton are an intriguing family of natural products, exhibiting wide systematic occurrences, large structural diversity, and multiple biological activities. Based on their structural characteristics, BPI alkaloids can be classified into chimonanthine-type BPI alkaloids, BPI diketopiperazines, and BPI epipolythiodiketopiperazines. These intricate molecules have captivated great attention soon after their isolation and identification in the 1960s. Due to the structural complexity, the total synthesis of these cyclotryptamine alkaloids is challenging. Nevertheless, remarkable progress has been achieved in the last six decades; in particular, several methods have been successfully established for the construction of vicinal all-carbon quaternary stereocenters. In this review, the structural diversity and chemical synthesis of these BPI alkaloids were summarized. BPI alkaloids are mainly synthesized by the methods of oxidative dimerization, reductive dimerization, and alkylation of bisoxindole. The purpose of this review is to present overall strategies for assembling the BPI skeleton and efforts towards controlling the stereocenters.

Genetic Studies of Natural Glycosphingolipid Ligands for NKT Cells.

Glycosphingolipids (GSL) are natural ligands of NKT cells. Several laboratories have reported the in vitro activity of isoglobotriosylceramide (iGb3) in stimulating NKT cells. However, the knockout mice of iGb3 synthase showed no deficiency in development and function of NKT cells. There is a lack of knowledge on the genetics of redundant natural glycosphingolipid ligands. We have identified additional glycosphingolipid with stimulatory activity to NKT cells, including fucosyl lactosylceramide (H antigen). Here we describe the procedures to generate mice with deficiencies in Fut1, Fut2, and Sec1 genes to deplete H antigen through BAC engineering for the generation of ES cell-targeting construct, as well as the mice with deficiency of both blood group H-GSL ligand and isoglobotriosylceramide.

Tandem Photoredox-Chiral Phosphoric Acid Catalyzed Radical-Radical Cross-Coupling for Enantioselective Synthesis of 3-Hydroxyoxindoles.

A photochemical protocol that couples diarylamines and α-ketoesters to afford the chiral 3-hydroxyoxindoles through tandem photoredox and chiral phosphoric acid catalysis is developed. The reaction involves an enantioselective photochemical radical-radical cross-coupling process. The chiral phosphoric acid is discovered to play crucial roles by decreasing the reductive potentials of α-ketoesters and stereocontrolling the downstream asymmetric radical-radical cross-coupling via the formation of pentacoordinate complex.

Acylation of Arenes with Aldehydes through Dual C-H Activations by Merging Photocatalysis and Palladium Catalysis.

An acylation of arenes with aldehydes through dual C-H activations at room temperature is reported. The acylation was initiated by phenanthraquinone-catalyzed hydrogen atom transfer from aldehyde under visible light irradiation. The aldehyde-derived acyl radical merged with palladium-catalyzed activation of arenes to afford the cross coupling products.

Nitrogen-Centered Radical-Mediated Cascade Amidoglycosylation of Glycals.

A nitrogen-centered radical-mediated strategy for preparing 1,2-trans-2-amino-2-deoxyglycosides in one step was established. The cascade amidoglycosylation was initiated by a benzenesulfonimide radical generated from NFSI under the catalytic reduction of TEMPO. The benzenesulfonimide radical was electrophilically added to the glycals, and then the resulting glycosidic radical was converted to oxocarbenium upon oxidation by TEMPO+, which enabled the following anomeric specific glycosylation.

Chichibabin pyridinium synthesis via oxidative decarboxylation of photoexcited α-enamine acids.

A visible light-induced decarboxylative Chichibabin pyridinium synthesis between α-amino acids and aldehydes was developed. When the in situ generated α-enamine acids were photoexcited, they were oxidized by aerobic oxygen to give radical cation species. After decarboxylation and further oxidation, the generated iminium undergoes Chichibabin cyclization to afford pyridiniums. This photochemical protocol enables the synthesis of various tetra-substituted pyridiniums and related natural products in one-step.

A photoexcited halogen-bonded EDA complex of the thiophenolate anion with iodobenzene for C(sp3)-H activation and thiolation.

Thiophenol was discovered to form an EDA complex with iodobenzene through halogen bonding interactions upon treatment with KOH. A direct photochemical thiolation of C(sp3)-H bond-containing etheric, allylic, and benzylic substrates with thiophenol was developed. The reaction proceeded on the basis of the in situ generation of a thiyl radical and aryl radical through single electron transfer between the photoexcited thiophenolate anion and aryl iodide EDA complex. Then a C(sp3) centred-radical was formed by aryl radical-mediated hydrogen atom transfer and the thiolation products were delivered via a radical-radical cross-coupling with the thiyl radical.

Correction: A photoexcited halogen-bonded EDA complex of the thiophenolate anion with iodobenzene for C(sp3)-H activation and thiolation.

[This corrects the article DOI: 10.1039/D1SC03667J.].

Photochemical α-carboxyalkylation of tryptophols and tryptamines via C-H functionalization.

A process for the α-carboxyalkylation of tryptophols and tryptamines by the functionalization of C-H bonds under visible light irradiation has been developed. The photochemical strategy activated the C-Br bonds of α-bromo-alkylcarboxylic esters to provide carbon-centered radicals under the catalysis of Ir(iii) photocatalyst and coupled with indole derivatives. This methodology displayed wide functional group tolerance and excellent regioselectivity, and was applied to the late-stage functionalization and preparation of indole-containing hybrids.

Three-Component Minisci Reaction with 1,3-Dicarbonyl Compounds Induced by Visible Light.

A three-component Minisci reaction coupling of 1,3-dicarbonyl compounds with vinyl ethers and quinolines or isoquinolines under visible light is developed. The 1,3-dicarbonyl compound undergoes single-electron oxidation to afford an electrophilic 1,3-dicarbonyl radical under visible light irradiation. Due to the polarity of the free radical, the electrophilic radical adds to the electron-rich olefin to afford the nucleophilic radical. It coupled with the heteroarene to afford the three-component coupling products.

Enantioselective Synthesis of Spiroindolines via Cascade Isomerization/Spirocyclization/Dearomatization Reaction.

The spiroindoline skeleton featured with 2,7-diazaspiro[4.4]nonane exists in various structurally intricate and biologically active monoterpene indole alkaloids. A catalytic asymmetric cascade enamine isomerization/spirocyclization/dearomatization succession to construct the spiroindoline was developed, which employed the indolyl dihydropyridine as a substrate under catalysis of the chiral phosphoric acid. This cascade reaction provided various spiroindolines in both diastereoselective and enantionselective fashions.