Diastereoselective Synthesis of Substituted Tetrahydrothiophenes and -thiopyrans via Thia-Prins Cyclization Reaction

Abstract

Tetrahydrothiophenes and -thiopyrans have been efficiently synthesized from thioacrylates via thia-Prins cyclization reaction mediated by trimethylsilyltrifluoromethanesulfonate with good diastereoselectivity and in good to high yields.

Bismuth(III)‐Triflate‐Catalyzed Highly Diastereoselective Synthesis of Substituted Tetrahydrothiophene via Tandem Isomerization, Michael and Aldol Reactions

“…In continuation of our interest in the synthesis of sulfur heterocyclic compounds, [23,24] we envisioned that β,γ-unsaturated ketone, 1-(4-chlorophenyl)but-3-en-1-one (1 b) under Lewis acidic conditions would generate enolate which will react with 1,4-dithiane-2,5-diol (2) in an aldol type fashion to give intermediate hydroxy ketone 3 which after Michael reaction will give tetrahydrothiophene 4 b (Scheme 1). However, in contrast, when the reaction was performed with 10 mol% of Bi (OTf) 3 in dichloromethane (DCM), compound 5 b was obtained as a single diastereomer in 25% yield after 60 h. Increasing the amount of Bi(OTf) 3 to 30 mol% gave 60% yield (entry 2, Table 1), and further increase of Bi(OTf) 3 to one equivalent could not enhance the yield even after 60 h, (entry 4, Table 1).…”

“…The sulfur analogs of oligosaccharides are known to be potential enzyme inhibitors . There are numerous methods for the synthesis of tertrahydrothiophenes, namely, intramolecular ring‐opening of epoxides by thiolates, hydrothiolation of nonactivated olefins, photolysis of diazo compounds, and thia‐Prins cyclization reactions . Tetrahydrothiophenes are also synthesized using domino Michael‐aldol and double Michael reactions.…”

Synthesis of Heterocyclic Scaffolds via Prins, Oxonium-Ene and Related Cyclization Reactions

“…We also studied the reaction of thioacrylates 74 (similar to acrylyl enol ethers) under the same reaction conditions and observed the formation of tetrahydrothiophenes 75 and tetrahydrothiopyrans 76 in moderate to good yields and high diastereoselectivities (Scheme 42 ). 54 Both aromatic and aliphatic substituents on the alkyne side chain and branched chain gave good yields. Electron-withdrawing groups on the aromatic ring gave better yields compared to electron-donating groups.…”