Dihydrothiepins

Other interesting three-component cycloadditions are the following Sulfur dioxide and diazo compounds lead to episulfones (equation 75)436—in a special case to 4,5-dihydrothiepine S,S-dioxides437 sulfur dioxide, ketene, and arylimine lead to thiazole derivatives438 (equation 76) sulfur dioxide, quinone, and alkenes lead to benzoxathiane derivatives439 (equation 77). 

Dihydrothiophene-1,1-dioxides (42) and 2,17-dihydrothiepin-1,1-dioxides (43) undergo analogous 1,4 and 1,6 eliminations, respectively (see also 17-38). These are concerted reactions and, as predicted by the orbital-symmetry rules (p. 1067), the former is a suprafacial process and the latter an antarafacial process. The rules also predict that elimination of SO2 from episulfones cannot take place by a concerted mechanism (except antarafacially, which is unlikely for such a small ring), and the evidence shows that this reaction occurs by a non-concerted pathway.The eliminations of SO2 from 42 and 43 are examples of cheletropic reactions, which are defined as reactions in which two a bonds that terminate at a single atom (in this case the sulfur atom) are made or broken in concert. 

The first synthesis of thiepin 1,1-dioxide (131) was performed by Mock in 1967 75>. With exess bromine in chloroform 2,7-dihydrothiepin 1,1-dioxide (129), prepared by 1,6-addition of sulfur dioxide to m-hexatriene, gave a dibromide 130 which, on treatment with two equivalents of triethylamine, afforded 131. Upon catalytic reduction, 131 rapidly absorbed three molar equivalents of hydrogen to yield hexahydrothiepin 1,1-dioxide (132). The 1,1-dioxide 131 is a fairly stable compound ... 

An alternative synthesis of thiepin 1,1-dioxide (131) has also been reported (Paquette, L. A., Maiorana, S. J. Chem. Soc. Chem. Commun. 1971, 313). Thus, the reaction of vinyldiazomethane with sulfur dioxide yields 4,5-dihydrothiepin 1,1-dioxide which was converted to 131 by bromination (NBS) and dehydrobromina-tion (Et3N) sequence. 

A quantum-chemical study has been undertaken on the isomerization of ctx-1-vinyl-, -1-formyl-, -1-thioformyl-, and -l-iminomethyl-2-vinylcyclopropane to cyclohepta-1,4-diene, 2,5-dihydrooxepine, 2,5-dihydrothiepine, and 2,5-dihydroaze-pine, respectively. Reaction pathways for circumambulatory rearrangements of main group migrants (NO, PO, NCS, SCN, NCO, OCN, SR, Cl, Br, and XX where X... 

A further example of a concerted thermal elimination reaction of a thiepane derivative was the formation of c/s-hexatriene and the extrusion of sulfur dioxide from heating 2,7-dihydrothiepin 1,1-dioxide (116) (67JA1281). That this reaction was under orbital symmetry control was deduced from the results obtained by heating cis- (117) and trans-... 

A double nucleophilic substitution reaction on 1,6-dibromohexane with sodium sulfide has been found to give an acceptable yield (59%) of the thiepane (35 equation 62) (81SC409). The reversible 1,6-addition of sulfur dioxide to ds-hexatriene (equation 63) provides a convenient synthetic route to the 2,7-dihydrothiepin 1,1-dioxide (116) (67JA1281). 

The mechanism of thermal isomerization of the cyclobutene compound in equation (74) to thiepin (50) is directly analogous to that found in the synthesis of dihydrothiepins (221) and (222 equation 65). Compound (50) was the first monocyclic thiepin to have been identified (74T2093). This synthetic route has also been applied to thiepin (148) (74T2431). 

These direct metallation-alkylation reactions of sulfolene and dihydrothiepin dioxide are incentives for future new synthetic applications of the associated cheletropic processes. 

The higher homologue of 3-sulfolene, 2,7-dihydrothiepin-l,1-dioxide could be similarly metallated at low temperatures. Reaction with reactive electrophiles followed by extrusion of sulfur dioxide led [549] to the corresponding hexatriene derivatives, as in the stereoselective synthesis of (Z,E)-l,3,5-decatriene (considered as an undecatriene in the publication) shown here. 

Ramberg-Backlund rearrangement of fused dihydrothiepine 1,1-dioxides obtained via [6n+4n] cycloaddition (Section 13.03.5.2) led to benzannulated polycycles <1996JOC7644, 1999JA8237>. The rearrangement was conducted by the sequential treatment of dihydrothiepin 1,1-dioxides 102-106 with Bu OK and A-chlorosuccinimide (NCS) or. V-iodosiiccinimidc (NIS) at —105 °C, followed by the addition of another equivalent of the base (Scheme 13). The benzannulated product 111 was transformed to (-l-)-estradiol 112. 

A new method for a-phenol annulation involving base-induced cycloaromatization of readily available 4-bis (methylthio)-3-buten-2-one 114 was applied to 3,4-dihydro-l-benzothiepin-5(2//)-one 113 (Scheme 14) <2002JOC5398>. Equimolar quantities of the benzothiepinone 113 and 114 in the presence of sodium hydride were stirred in dimethylformamide (DMF) at 25 °C. Treatment of the reaction mixture with/>-toluenesulfonic acid in refluxing benzene furnished the phenol-annulated dihydrothiepine 116 in 62% yield. The reaction sequence involved formation of conjugate addition-elimination adduct 115, followed by intramolecular aldol condensation and cycloaromatization, affording 116. 

In the lithiation step (Equation 13), a reductive opening of the dihydrothiepine took place giving possible intermediate 121, which by reaction with the carbonyl compound R R2CO used as electrophile gave the second intermediate 122, precursor of products 120 by acidic hydrolysis. A variant of the lithiation of the starting material 119 resulted when a second electrophile was introduced in the molecule. After the generation of the intermediate 122, instead of hydrolysis, a second lithiation took place at temperatures ranging between —78 and... 

The reaction of dibromides 191 and Li2S gave dihydrothiepines 192 in 66-82% yield (Equation 27) <2000H(53)897>. 

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