Cyclization 67 allylic sulfides

Thiochromans (1 R = H2) result from disproportionation of 2H- -benzothiopyrans (4) and also from thio-Claisen rearrangements of phenyl allyl sulfides. The first pathway was discovered by Tilak and Vaidya,24 who attempted to prepare one benzothiopyran (15) by cyclizing the /S-ketosulfide (14) in polyphosphoric acid (PPA), but obtained the thiochroman (16) and a benzothiopyrylium salt as in Eq. (5). This reaction involves25,26 an acid-promoted disproportionation... 

Cyclization of ketyl anions onto allyl sulfides or sulfones were reported to yield 2-vinylcyclopentananols according to equation 3088. 

Annelation.1 This reagent is used for conversion of 3-substituted aldehydes (or acetals) into methylenecyclohexanes. The conversion involves addition of the allylsilane group to the aldehyde or acetal to provide an adduct that undergoes radical cyclization via the allylic sulfide group. The phenylthio group is used to enhance 6-endo cyclization over the usual 5-exo cyclization. In addition it allows use of bis(tributyltin) as the initiator (14,173-174). Unfortunately the radical cyclization shows only slight stereoselectivity. 

Reaction of 2-bromoaryl allyl sulfides 445 with tributyltin hydride in the presence of AIBN gives dihydrobenzothio-phenes 446 via intramolecular free-radical i-endo-trig cyclization. In the case of 445 (R = Me), rearranged product 447 is also formed (Scheme 73) <1998JOC3318>. Similar synthesis of 449 <1998JOC4645> from 448 has been reported. 

Trost has reported the use of dithioacetals as initiators in vinylsilane-terminated cyclizations (Scheme 11). Reaction of the dimethyl thioketal (26) with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) led to the formation of the allylic sulfide (28) via a 2,3-sigmatropic rearrangement of the initially formed sulfonium salt (27a), which may have been catalyzed by complexation with excess DMTSF. 

The coupling reaction of epoxide 69 with the anion derived from the allyl sulfide 57, a system derived from geraniol, was accomplished in a 99% yield by employing 4 equivalents of the anion (Scheme 13). Protection of the alcohol as the MOM ether (95%), followed by debenzylation and removal of the phenylthio group under Birch conditions (76%) gave diene 70. Vanadium catalyzed oxidation and spontaneous cyclization of 70 imder acidic conditions afforded a diastereomeric mixture of tetraols 71 and 72 in 61% and 14% yields, respectively. 

Completely stereoselective cyclizations using formyl allyl sulfides and sulfones have been described. Optimum conditions involved the slow addition of a solution of the starting material in THF to a 0.1 M solution of Sml2 containing 8 equiv of HMPA in THF at -10 and -78 °C, respectively [64]. 

In 1982, Ueno reported the first uses of allylic sulfur compounds for carrying out the allylation of a carbon-centered radical [48], The reactions detailed are cycliza-tion reactions in which an aryl radical adds to an allylic sulfide to form either an indole or benzofuran product (Scheme 17). Tin, in the form of tributyltin hydride, was used to carry the radical chain. With low concentrations of tin hydride, yields of the desired products as high as 96% were observed. A more recent set of examples of cyclizations onto allylic sulfides was reported by Ward in 1991 [49]. 

To investigate whether the radical cations of the diazadithiafulvalenes would undergo eoupling with carbon radicals at a different rate than TTF+, eomparative experiments were performed with the allyl sulfide 99. This led to the products 100 and 101 as for TTF (Scheme 16). However the yield of the bicyclic produet was higher for the diaza compounds, indicating a slow-down in the kinetics of the recombination reaction. Although this is likely to be a fairly small change, it is clear that the modulation of kinetics in this way may be useful with radical-polar crossover reaetions to permit slower cyclizations to occur before recombination. 

Cyclization. Fused 1-vinylcyclopropanes are formed on lithiation of allyl sulfides that bear an alkenyl chain at the a-position. 

Treatment of bisbenzenesulfonylmethane and a ketone with Smia leads to a /3-hydroxy sulfone. Allylic sulfones are a source of allyl anions because they are cleaved by Sml2 in HMPA thus a new preparative method for homoallylic alcohols is available. However, the desulfurative cyclization of allylic sulfides toward a carbonyl group may belong to a different mechanistic category. 

Addition of the phenylthio radical to the alkenyl cyclopropane generates an a-alkoxy radical that can fragment to release benzophenone and an a-keto radical. This radical then adds to the a,p-unsaturated ester to give a new radical that can cyclize onto the allylic sulfide to give the mixture of diastereomeric cyclohexanones 10 (and releasing the phenylthio radical). See K. S. Feldman and A. K. K. Vong, Tetrahedron Lett., 31 (1990), 823. 

As for allyl sulfides (Section VIII.4.C), because of the possibility of competitive pathways in the cyclization of acetylenic thiols, and the small number of studies devoted to these cyclization processes, it is not possible at this time to suggest a rationale for the thio-Claisen rearrangement of propargyl... 

Allyl sulfides have been used in radical cyclization to control the regiochemistry in 6-endo ring closures. This, indeed was found to be the case when the enamine 181 was subjected to radical cyclization under high dilution conditions. Tlie etgoline 182 was isolated after successful S-eco-trig, 6-endo-trig, 6-endb-trig cyclization. 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

The amine 196 upon reaction with hydrogen sulfide in dimethylsulfoxide (DMSO) in the presence of base at 25-50 °C afforded the thiazine 197, allyl(2-mercaptopropyl)amine 198, and 3,7-dimethylperhydro[l,2,5]dithiazepine 199 in 10-17%, 2-31%, and 1-50% yields, respectively (Scheme 43) <2000RJC1243>. The formation of 199 is assumed via thiol 198, which reacted with a second hydrogen sulfide molecule to give dithiol 200. Subsequent oxidation of200 resulted in 199. In an alternative mechanistic pathway, the amine 196 can form the intermediate 201, which could cyclize to give 199. 

A series of 2,3 dihydrobenzothiophenes 451 have been synthesized by Ni-catalyzed electrochemical cyclization of allyl 2-haloaryl sulfides 450 (Equation 15) <2004SC3343>. 

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