Thiols in Ugi‐ and Passerini–Smiles‐Type Couplings

Abstract

International audienc

The Ugi–Smiles and Passerini–Smiles Couplings: A Story About Phenols in Isocyanide‐Based Multicomponent Reactions

“…The first successes with mercaptans emerged from the use of heterocyclic compounds. Indeed, different families of mercapto‐substituted six‐membered‐ring heterocycles underwent these couplings to form highly functionalized thiocarboxamides in single‐step manner 18. As observed with hydroxy‐substituted aromatics, 4‐mercaptopyridines and ‐quinolines reacted more smoothly than 2‐mercaptopyridines to give good isolated yields (Scheme ) 24.…”

“…The best results were obtained with thiosalicylic methyl ester, but in this case the reactions stopped before the Smiles rearrangement, with the corresponding thioimidates being isolated (Scheme 14). [18] These turned out to be rather stable, with no Smiles rearrangement being observed even under prolonged heating in toluene at reflux. In the light of these results, the nitro-substituted thiophenol probably promotes the condensation of the four reagents but the resulting thioimidate could be hydrolyzed prior to rearrangement.…”

“…Unfortunately, however, nitro‐substituted thiophenols afforded the desired adducts only in poor yields – less than 26 % (Scheme ). The best results were obtained with thiosalicylic methyl ester, but in this case the reactions stopped before the Smiles rearrangement, with the corresponding thioimidates being isolated (Scheme ) 18. These turned out to be rather stable, with no Smiles rearrangement being observed even under prolonged heating in toluene at reflux.…”

“…However, the most interesting results with thioaromatic compounds emerged from the use of those five‐membered‐ring heterocycles that turned out to undergo this reaction. Although only limited success was met with plain azoles – only 4‐alkyl‐3‐mercapto‐1,2,4‐triazoles were able to promote the thioimidate formation (Scheme )18 – benzo‐fused systems, such as 2‐mercaptobenzoxazoles and ‐benzothiazoles, widely employed in Julia olefination reactions, were used successfully. In both cases the reactions proceeded well, giving the desired N ‐benzo‐fused thiocarboxamides in good to excellent yields (Scheme ) 26.…”

Synthesis of New Pyrimido[4,5‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine Derivatives via S/N Smiles Rearrangement

“…Smiles type rearrangements have been proposed to occur with uracils , thiadiazoles , thiohydrazonates , anilines , and pyrimidines . They have also been reported to be involved in the synthesis of phenothiazines , dipyridothiazines , pyrido[1,4]‐ and benzo[ b ][1,4]‐thiazinones , α‐arylaminothiocarboxamides , and 2,4‐disubstituted piperidines . In the present work a facile S/N type Smiles rearrangement has occurred during heterocyclization to produce the products with regiochemistry B instead of A in Scheme and therefore the real reaction which has occurred is depicted in Scheme .…”