Copper(I)‐Promoted Synthesis of Highly Substituted and Functionalized Tetrahydrothiophenes

Abstract

Copper(I)‐promoted 5‐exo halogen‐atom‐transfer radical cyclization of 2,2,2‐trihaloethylallyl sulfides gave highly functionalized tetrahydrothiophenes in good to high yields. Stereochemical aspects of the diastereomeric mixtures of products formed under different reaction conditions were evaluated, and single‐crystal diffraction analysis and 2D NMR spectroscopic analysis were carried out. The synthetic application of α‐acetoxy tetrahydrothiophenes in the preparation of a dihydrothiophene has also been demonstrated.

Radical-Mediated Reactions of α-Bromo Aluminium Thioacetals, α-Bromothioesters, and Xanthates for Thiolactone Synthesis

“…Following generation of a tributyltin radical, this intermediate abstracts a bromine atom from the aluminium thioacetal to generate a carbon-centred radical α to the thioacetal ( Scheme 2 ). Contrary to what was observed during the cyclisation of trichloroacetals under atom transfer conditions [ 20 ], and despite the fact that the reaction was carried out at low temperature, the aluminium thioacetal subsequently collapses through a homolytic β-fragmentation pathway to generate an aluminium enolate and a thiyl radical, both of which may remain coordinated to the aluminium. The electron-rich alkene thus generated reacts with the electrophilic thiyl radical to give the thiol-ene addition product [ 22 , 23 ].…”

“…The instability of the aluminium complex and the dissociation of the aluminium enolate are the likely factors contributing to the low isolated yield of the radical rearrangement product 7 . However, in light of the results obtained by I. Markó et al demonstrating the thermal stability of this type of aluminium-thioacetal species, together with the successful cyclisation of protected thioacetals under atom-transfer conditions [ 20 ], the fragmentation of the aluminium-thioacetal at the low temperature employed during our reaction is more puzzling.…”

“…A dimeric structure was also suggested for the aluminium thioacetal species [ 17 ] and it is reasonable to assume that α-halo aluminium thioacetals could be stable enough to serve as precursors in a radical cyclisation. In this case, despite the formation of a beta-sulfanyl radical intermediate susceptible to fragmentation [ 18 , 19 ], the precedent in the literature led us to expect that this process would not compete with the desired cyclisation [ 20 ].…”

Chemo- and regioselective [3 + 2]-cycloadditions of thiocarbonyl ylides: crystal structures of trans-8-benzoyl-1,1,3,3-tetramethyl-7-trifluoromethyl-5-thiaspiro[3.4]octan-2-one and trans-3-benzoyl-2,2-diphenyl-4-(trifluoromethyl)tetrahydrothiophene

“…For example, Lewis acid-catalysed reactions of thiocarbonyl compounds with 'donor-acceptor cyclopropanes' have been reported (Augustin et al, 2017;Matsumoto et al, 2018). In addition, radical cyclizations (Ram et al, 2016) and 'sulfur Michael/Henry reactions' (Zhang et al, 2018) were elaborated as new approaches to tetrahydrothiophenes. Furthermore, analogous domino reactions, i.e.…”

“…The CSD contains crystal structure data with atomic coordinates for 3225 monomeric organic compounds with the string thiophene in the compound name, of which 70 are named as tetrahydrothiophenes and 32 contain no substituents on the ring S atom. Recently published monocyclic crystal structures of tetrahydrothiophenes include those of Duan et al 2017, Ram et al (2016), Zamberlan et al (2018) and Zhang et al (2018). Spirocyclic examples involving two cojoined fivemembered rings have been reported by Meninno et al (2017) and Wang et al (2018).…”