Thioketones cycloaddition

Thioketones of various types are readily available and are well documented as effective dienophiles. Representative thioketone cycloadditions are listed in Table 5-1. In general, it appears that thioketones usually add to most dienes in high yield at exceptionally low temperatures to afford stable adducts, although some of these adducts tend to undergo retro-Diels-Alder reactions. - Very little has been done toward establishing the regiochemical selectivity of thioketone additions to unsymmetrical 1,3-dienes, and the few such entries in Table 5-1 indicate that mixtures were obtained. The exo/endo stereochemistry of [4 + 2] cycloadditions with unsymmetrical thioketones has not been probed to date. It has been reported that Diels-Alder cycloadditions of thioketones can also be pho-tochemically induced. 

Tile behavior of /3-moiiooxo derivatives of 4-chlomaiioiies (27) toward morpholine was rather complex (98JOC9840). Tlius, the proposed thio-ketoiie 5-sulhde intermediates 28 would dimerize into either 1,2,4,5-tetrathianes 29 in a two-step manner or to 1,3,4,5,6-oxatetrathiocins 30 by a [5 + 3] cycloaddition. Meanwhile, the formation of oxadithiins 31 and 1,2,4-trithiolanes 32 is suggestive of the disproportionation of 28 into the thioke-tones 33 and the thioketone 5 -disulhdes 34. Tlie oxadithiins 31 correspond to a Diels-Alder dimer of 33, and the 1,2,4-trithiolanes 32 correspond to cycloadducts of 33 and 34. 

Tlie thermal reaction of dithiiranes is of particular interest in relation with the dithiirane/thioketone 5-sulfide manifold. Heating 5-oxodithiiranes (4) in solution led to both isomerization to 6,7-dithia-8-oxabicyclo[3.2.1]-octanes 74 and desulfurization to 5-oxothiones 75, the ratio of which was dependent on the reaction conditions employed. The intramolecular [3 + 2] cycloaddition of the thioketone 5-sulfide 76, generated by ring-opening, provides a straightforward explanation for the formation of 74. Meanwhile, 75 is probably formed by a nucleophilic attack on the sulfur atom by another molecule of 4 and/or by elemental sulfur formed during the reaction. 

A sequence of two thermal intramolecular cycloadditions has been used to develop a short synthetic approach to tetrahydrothiopyrans [122], The multiple process includes an m m-hetero- and an intramolecular-carbon Diels-Alder reaction. An intramolecular /zctcro-Diels-Alder reaction of divinyl-thioketone 134 afforded a 9 1 mixture of cycloadducts 135 and 136 which then underwent a second intramolecular cycloaddition which syn o H-2)-exo-diastereoselectively led to hexacyclic tetrahydrothiopyrans 137 and 138, respectively (Scheme 2.51). 

Dihydrothiopyrans have also been prepared by cycloaddition between a,jS-unsaturated thioketones and carbonyl-activated dienophiles under Lewis-acid catalysis [78]. A marked dependence of the reaction yield on the catalyst was observed. The results of the cycloaddition reaction of thioketone 77 with methyl metacrylate, catalyzed by different catalysts, are illustrated in Equation 3.24. 

Polymerization and oligomerization reactions. l-FIalogenopropane-2-thiones give homopolycondensation,10 in different conditions l-chloropropane-2-thi-one11 forms a polymer or a cyclic trimer. a-Oxothioketones12 15 form dimers, by [4+2] unsymmetrical Diels Alder cycloaddition (Scheme 7). a,p-Unsatu-rated thioketones,16 Scheme 3 E = S, form dimers via head-to-head (R1 = Ph, R2 = Me) and head-to-tail (R1 = R2 = Ph), while selenoketones, E = Se, dimerize17 via head-to-head . 

Six-membered rings. Thioketones react as dienophiles with conjugated dienes81,87 92 in Diels Alder [4+2] cycloadditions to form 3,6-dihydro-2H-thiopyrans regio- and stereo-selectivitely. 4 and 6 reacting with differently substituted 1,3-butadienes, Scheme 12, have shown a superdienophile activity.87 89... 

When the C=S bond is conjugated with double or triple bonds, thioketones can also behave as heterodienes93 104 towards dienophiles. If thioketone contains an aromatic ring, the [4+2] cycloaddition can be followed by 1,3-protot-ropy to restore the ring aromaticity,105 108 forming lH-2-benzothiopyrans as shown in Scheme 13, where 4,4 dimethoxythiobenzophenone reacts with the dienophile dimethyl acetylenedicarboxylate (DMAD).105... 

Whenever benzyne is expected to undergo a [2+2] cycloaddition as with ketones,109 it behaves as a dienophile with aromatic thioketones. Reaction of thiobenzophenones with benzyne yields the [4+2] cycloadducts and 1H-2-benzothiopyrans.110,111 Sterically congested thiones,111 thiopivalophenones and 2, react with benzyne to give the [2+2] adducts, 2H-l-benzothietes. 

Many cycloadditions of nitrones86,172 174 and thiones give cycloaddition-cycloreversion equilibria. A-Methyl-C,C-diphenyl- and A-methyl-C-phenyl-nitrones, react with aliphatic thiones forming 1,4,2-oxathiazolidines, while 4 does not afford a cycloadduct.172 A-Methyl-C,C-2,2,4,4-tetramethyl-3-cyclo-butanonenitrone reacts with alicyclic thioketones to give 1,4,2-oxathiazolidines,174 while with 4 it enters into a metathesis reaction. 

This chapter deals with [2 + 2]cycloadditions of various chromophors to an olefinic double bond with formation of a four-membered ring, with reactions proceeding as well in an intermolecular as in an intramolecular pattern. Due to the variety of the starting materials available (ketones, enones, olefins, imines, thioketones, etc.. . .), due to the diversity of products obtained, and last but not least, due to the fact that cyclobutanes and oxetanes are not accessible by such a simple one-step transformation in a non-photo-chemical reaction, the [2+2]photocycloaddition has become equivalent to the (thermal) Diels-Alder reaction in importance as for ring construction in organic synthesis. 

N-benzyladamantyl-2-imines, and 2-methyleneadamantanes were studied (352, 353). In particular, X-ray single-crystal analysis confirmed the configuration of the oxathiazoline 185, resulting from the favored attack of nitrile oxide on the 5-fluoroadamantane-2-thione. 2-Silyl-substituted oxathiazole 186 was synthesized by the 1,3-dipolar cycloaddition reaction of phenyl triphenylsilyl thioketone with 4-chlorobenzonitrile oxide (354). 

A very similar reaction to that of Pechmann and Nold but which probably does not proceed through a dipolar cycloaddition manifold is the formation of 1,2,3-thiadiazole (6) via a thionoester and lithium trimethylsilyldiazomethane (Equation (17)) <86H(24)589>. Lithium trimethylsilyl-diazomethane also reacts with thioketones to produce 1,2,3-thiadiazoles <87H(26)1467>. 

Many cycloaddition reactions have been carried out with ketenes and thioketones. The products are thiolactones (52). Hexafluorothioacetone and diphenylketene, however, do not undergo cycloaddition even after prolonged heating at 100°C. Good results can be obtained when the more stable dimer of this fluorinated thioketone (53) is used. Anionic monomer 54 could be released by the action of potassium fluoride in an aprotic solvent. Two-step cycloaddition to diphenylketene yields ketone 55. 

Photocycloaddition of thiones to alkenes is the most popular and fruitful method for the preparation of the thietane system. In analogy to the formation of the oxetanes by cycloaddition of the electronic excited ( ,tc ) carbonyls, thietanes can be expected to arise photochemically from aromatic thioketones and substituted olefins as well as 1,2- and 1,3-dienes. ° Thiobenzophenone serves as a source of a sulfur atom and, because of its blue color, which disappears on photocycloaddition, permits exact control over the reaction time. A mixture of thiobenzophenone and a-phellandrene must be irradiated for 70 hr before the blue color disappears (Eq. 2) and... 

Heteroatomic dipolarophiles are competent in the dipolar cycloaddition of nitronates. The in situ generated thioaldehydes and thioketones react with sUyl nitronate 120 to afford the 1,4,2-oxathiazolidine in good yield (Table 2.36) (113-116). 

For preparative purposes, the reaction of thiocarbonyl ylides with carbonyl compounds can be considered as an alternative method for the synthesis of 1,3-oxathiolanes. Aromatic aldehydes, chloral, glyoxalates, mesoxalates, pyruvates as well as their 3,3,3-trifluoro analogues are good intercepting reagents for thioketone (5)-methylides (36,111,130,163). All of these [3 + 2] cycloadditions occur in a regioselective manner to produce products of type 123 and 124. 

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

Some examples dealing with the [4 + 2] cycloaddition of ketenimines have been recorded (Scheme 58). Thus, thioketones and ynamines reacted with N-aryl ketenimines 257 through the carbon—nitrogen and the conjugated aromatic carbon—carbon double bonds to yield benzothiazine derivatives 258 (80JOC3766 82JOC3998) and substituted quinolines 259 (73JA5417), respectively. Simple ketenimines 261 were formed by reaction... 

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