Reaction of lithioalkoxyallenes with isothio-cyanates: Synthesis of pyrroles and 5,6-dihydropyridines

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

“…The low-temperature reactions of metalloalkynes and metallodienes with isothiocyanates made not only the pyrroles, thiophenes, and thietanes discussed above but also such valuable nitrogen-containing heterocycles as 2,3-and 1,2-dihydropyridines, pyridines, dihydropyridinones, and pyridinethiones accessible [99,101,130,142,[375][376][377][378][379][380][381][382][383][384][385][386][387][388][389][390][391][392]. When heated in the absence of a catalyst (salts of monovalent copper) 1-aza-1,3,4-trienes 137, formed during the reaction of lithiated alkoxyallenes with aliphatic isothiocyanates, go through two competing processes -intramolecular cyclization to pyrrole and isomerisation (through a [1,5]-H sigmatropic shift) to 2-aza-1,3,5-trienes 138, the electrocyclization of which leads to a new type of 5,6-disubstituted 2,3-dihydropyridines 139 [99,130,[375][376][377][378].…”

“…When heated in the absence of a catalyst (salts of monovalent copper) 1-aza-1,3,4-trienes 137, formed during the reaction of lithiated alkoxyallenes with aliphatic isothiocyanates, go through two competing processes -intramolecular cyclization to pyrrole and isomerisation (through a [1,5]-H sigmatropic shift) to 2-aza-1,3,5-trienes 138, the electrocyclization of which leads to a new type of 5,6-disubstituted 2,3-dihydropyridines 139 [99,130,[375][376][377][378]. All stages of the process -from lithiation of the allene to the formation of the heterocyclic structures -are carried out in one reactor without isolation of the intermediates.…”

First example of 2,3-dihydropyridines aromatization through hemiacetal elimination

“…There with the acetalpyrrole 5 did not under any changes both in the course of the reaction under discussion and in the subsequent separation of its mixture with pyridine 6 (using hydrochloric acid [16,17]). …”

“…Since the isolation of 2,3-dihydropyridine 4 from the mixture with pyrrole 5 by the previously developed method (with the use of HCl) [16,17] was impossible in this case (as the removal occurred of the acetal protection from the dihydropyridine-3-ol with the formation of 6-methyl-2-(methylsulfanyl)-5,6-dihydro-3(4Н)-pyridinone [18]), we subjected to the treatment with potassium tert-butoxide the mixture of compounds 4 and 5. There with the acetalpyrrole 5 did not under any changes both in the course of the reaction under discussion and in the subsequent separation of its mixture with pyridine 6 (using hydrochloric acid [16,17]).…”