Visible light-mediated halogenation of organic compounds.

The use of visible light and photoredox catalysis emerged as a powerful and sustainable tool for organic synthesis, showing high value for distinctly different ways of bond creation. Halogenated compounds are the cornerstone of contemporary organic synthesis: it is almost impossible to develop a route towards a pharmaceutical reagent, agrochemical, natural product, etc. without the involvement of halogen-containing intermediates. Moreover, the halogenated derivatives as final products became indispensable for drug discovery and materials science. The idea of this review is to understand and summarise the impact of visible light-promoted chemistry on halogenation and halofunctionalisation reactions.

Azo Coupling of Indoles Revisited: Synthesis of Biindolyl Photoswitches via the Azo-Coupling/C-H Functionalization Domino Approach.

When azo coupling of aryldiazonium salts with indoles was carried out in aprotic nonpolar solvent on air, a pseudo-three-component reaction has been discovered. Azo coupling is followed by a nucleophilic addition of a second indole unit to the indolium intermediate; aromatization and oxidation are achieved under air.

Chemoselective Divergent Transformations of N-(Propargyl)indole-2-carbonitriles with Nitrogen Nucleophiles: Alkyne Hydroamination or Domino Cyclizations.

Interactions of N-(propargyl)indole-2-carbonitriles with nitrogen nucleophiles were studied. It was found that lithium hexamethyldisilazane (LiHMDS)-promoted reactions give mixtures of two product types, originating from an initial attack onto carbon-carbon or carbon-nitrogen triple bonds. Performing the reaction at reduced temperature and in the presence of catalytic amounts of LiHMDS delivered alkyne hydroamination products exclusively. On the contrary, the one-pot reaction of N-(propargyl)indole-2-carbonitriles with methanol and LiHMDS on heating, followed by the addition of a nitrogen nucleophile, allowed a selective domino cyclization sequence toward 1-aminopyrazino[1,2-a]indoles. Anilines and nitrogen heterocycles could be employed as N-nucleophiles to obtain products of both types. Moreover, an alternative one-pot route toward a third product type has been developed. When N-(propargyl)indole-2-carbonitrile was first combined with aniline and LiHMDS at reduced temperature, further heating of the in situ generated hydroamination product led to the intramolecular cyclization into 1-imino-2-phenylpyrazino[1,2-a]indoles. Thus, chemodivergent transformations of the same starting material into three compound classes were investigated. The possible reaction routes were studied, and N-(allenyl)indole-2-carbonitrile was identified as the key intermediate. Acyclic and cyclic products exhibit fluorescence emission in the blue to green range.

Photoredox-Catalyzed Hydrosulfonylation of Arylallenes.

(Het)Arylallenes undergo hydrosulfonylation under photoredox-catalyzed conditions. The reaction gives vinyl sulfones in a regio- and diastereoselective manner, employing sodium sulfinates as the sulfonyl source and eosin Y as the photocatalyst. Indol-1-yl, pyrrol-1-yl, phenyl, and naphtylallenes might be used. Aliphatic allenes are incompatible with the reaction conditions.

Reductive domino reaction to access chromeno[2,3-c]isoquinoline-5-amines with antiproliferative activities against human tumor cells.

An interaction of homophthalonitrile with salicylaldehydes proceeds as a novel domino reaction and results in the formation of nineteen 12H-chromeno[2,3-c]isoquinoline-5-amine derivatives. Four new bonds and two cycles are forged in a single synthetic operation, employing cheap and eco-friendly ammonium formate, acting both as a catalyst and a reducing agent. The in vitro cytotoxicity tests revealed antiproliferative activities against five human tumor cell lines, including the cisplatin-resistant ovarian carcinoma one (A2780cp8), with inhibitory potency data (IC50) in the low micromolar range in most cases. Molecular docking calculations and fluorescence quenching studies revealed possible binding properties with DNA of the active compounds.

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines.

The sequential three-component reaction between o-hydroxybenzaldehydes, N-(cyanomethyl)pyridinium salts and a nucleophile towards substituted chromenoimidazopyridines under oxidative conditions has been developed. The employment of Mn(OAc)3·2H2O or KMnO4 as stoichiometric oxidants allowed the use of a wide range of nucleophiles, such as nitromethane, (aza)indoles, pyrroles, phenols, pyrazole, indazole and diethyl malonate. The formation of the target compounds presumably proceeds through a domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction sequence.

Photoredox-Catalyzed Chlorotrifluoromethylation of Arylallenes: Synthesis of a Trifluoromethyl Building Block.

A new class of trifluoromethyl building blocks─2-trifluoromethyl allyl chlorides─have been obtained through a photoredox-catalyzed chlorotrifluoromethylation of aryl allenes. The reaction proceeded in a regio- and stereoselective manner. A trifluoromethylated analog of the flunarizine drug was synthesized.

Electrochemical Decarbonylative Aminosulfonylation of Alkynes with Sulfinates and N-(Formyl)anilides.

An unprecedented electrochemical three-component reaction of phenylacetylene, sulfinate, and N-(formyl)anilide was discovered. The transformation occurs in an undivided cell with a graphite anode and cathode in DMF in the presence of tetrabutylammonium iodide as an electrolyte. The addition of silver(I) oxide and catalytic amounts of iodine facilitated the reaction significantly. The transformation was also carried out under photoredox-catalyzed conditions.

Homophtalonitrile for Multicomponent Reactions: Syntheses and Optical Properties of o-Cyanophenyl- or Indol-3-yl-Substituted Chromeno[2,3-c]isoquinolin-5-Amines.

Malononitrile is a useful reagent for multicomponent reactions with hundreds of methods developed. In this paper, we suggest α-(cyano)-o-tolunitrile (homophtalonitrile) to work as a vinylogous malononitrile. Thus, a organocatalytic pseudo-three-component reaction of homopthalonitrile (2 equiv) and o-hydroxybenzaldehyde, leading to the diastereoselective formation of 5-amino-12H-chromeno[2,3-c]isoquinolin-12-yl)(cyano)methyl)benzonitriles, was discovered. The possibility to employ other nucleophiles was demonstrated for indoles, and a sequential three-component reaction of homophtalonitrile, o-hydroxybenzaldehyde, and (aza)indole, giving 12-(1H-Indol-3-yl)-12H-chromeno[2,3-c]isoquinolin-5-amines, was developed. The photophysical properties of the synthesized compounds have been studied, revealing high fluorescence quantum yields (42-70 %) for indol-3-yl substituted 12H-chromeno[2,3-c]isoquinolin-5-amines and reversible fluorescence quenching under acidic conditions.