Catalyst- and solvent-free regiospecific SNHAr phosphinylation of pyridines with H-phosphinates mediated by benzoylphenylacetylene.

Pyridines undergo a facile SNHAr phosphinylation with H-phosphinates under catalyst- and solvent-free conditions (50-55 °C) in the presence of benzoylphenylacetylene to afford 4-phosphinylpyridines in up to 68% yield. In this reaction, benzoylphenylacetylene activates the pyridine ring by the formation of a 1,3(4)-dipolar complex, deprotonates H-phosphinates to generate P-centered anions and finally acts as an oxidizer, being eliminated from an intermediate ion pair. Terminal electron-deficient acetylenes (methyl propiolate and benzoylacetylene) are inefficient as mediators in the above SNHAr process.

Dihydropyrrole-3-thiones: one-pot synthesis from propargylamines, acyl chlorides and sodium sulfide.

An efficient one-pot synthesis of 1,2,5-trisubstituted-1,2-dihydro-3H-pyrrole-3-thiones (up to 91% yield), representatives of essentially new heterocyclic systems, by the successive treatment of available propargylamines with acyl chlorides (PdCl2/CuI/Ph3P/Et3N, toluene, 40-45 °C, 3 h) and sodium sulfide (Na2S·9H2O, EtOH, 20-25 °C, 7 h) has been developed. The synthesis comprises the addition of sulfide anions to the formed aminoacetylenic ketones followed by dehydrative cyclization of the prototropically rearranged adducts.

Oxidative cross-coupling of secondary phosphine chalcogenides with amino alcohols and aminophenols: aspects of the reaction chemoselectivity.

Secondary phosphine chalcogenides react with primary amino alcohols under mild conditions (room temperature, molar ratio of the initial reagents 1 : 1) in a CCl4/Et3N oxidizing system to chemoselectively deliver amides of chalcogenophosphinic acids with free OH groups. Under similar conditions, mono-cross-coupling between secondary phosphine chalcogenides and 1,2- or 1,3-aminophenols proceeds only with the participation of phenolic hydroxyl to give aminophenylchalcogenophosphinic O-esters. The yields of the synthesized functional amides or esters are 60-85%.

Catalyst-Free Double CH-Functionalization of Quinolines with Phosphine Oxides via Two SNHAr Reaction Sequences.

Quinolines undergo catalyst-free double CH-functionalization upon treatment with secondary phosphine oxides (70-75 °C, 20-48 h) followed by oxidation of the intermediate 2,4-bisphosphoryltetrahydroquinolines with chloranil. The yields of the target 2,4-bisphosphorylated quinolines are up to 77%. Thus, a double-SNHAr reaction sequence in the same molecule of quinoline has been realized. In the case of 2,4-bisphenylphosphoryltetrahydroquinolines, the aromatization occurs with elimination of one molecule of diphenylphosphine oxide to afford the products of monofunctionalization, 4-diphenylphosphorylquinolines, in 40-45% yields.

Acetylene-Triggered Reductive Incorporation of Phosphine Chalcogenides into a Quinoline Scaffold: Toward SNHAr Reaction.

Quinolines react with acylacetylenes and secondary phosphine chalcogenides at 20-75 °C to afford N-acylvinyl-2(1)-chalcogenophosphoryldihydroquinolines in good and excellent yields. Unlike the pyridine-derived similar intermediates, which eliminate E-alkenes to give aromatic chalcogenophosphorylpyridines, thereby completing SNHAr reaction, with quinolines, the reaction stops at the formation of the above phosphorylated N-acylvinyl-dihydroquinolines, thus representing a pendant SNHAr process. This reaction opens a one-pot atom-economic single-step access to pharmaceutically targeted phosphorylated functionalized dihydroquinolines and isoquinolines.

Catalyst-Free Phosphorylation of Acridine with Secondary Phosphine Chalcogenides: Nucleophilic Addition vs SNHAr Reaction.

Acridine adds secondary phosphine chalcogenides HP(X)R2 (X = O, S, Se; R = Ar, ArAlk) under catalyst-free conditions at 70-75 °C (both in the presence and absence of the electron-deficient acetylenes) to give 9-chalcogenophosphoryl-9,10-dihydroacridines in 61-94% yields. This contrasts with pyridines, which under similar conditions undergo an SNHAr reaction, wherein electron-deficient acetylenes play the role of oxidants. For acridine, the SNHAr step has been accomplished by the oxidation of the intermediate 9-phosphoryl-9,10-dihydroacridines (X = O) with chloranil.

Metal-free site selective cross-coupling of pyridines with secondary phosphine chalcogenides using acylacetylenes as oxidants.

Pyridines undergo site selective cross-coupling with secondary phosphine chalcogenides (oxides, sulfides, and selenides) in the presence of acylphenylacetylenes under metal-free mild conditions (70-75 °C, MeCN) to afford 4-chalcogenophosphoryl pyridines in up to 71% yield. In this new type of SNHAr reaction acylacetylenes act as oxidants, being stereoselectively reduced to the corresponding olefins of the E-configuration.