Search

The reactions of aryl (selenophen-2-yl) thioketones with CH2N2 occur with spontaneous elimination of N2, even at low temperature (−65°), to give regioselectively sterically crowded 4,4,5,5-tetrasubstituted 1,3-dithiolanes and/or a novel type of twelve-membered dithia-diselena heterocycles as dimers of the transient thiocarbonyl S-methanides. The ratio of these products depends on the type of substituent located at C(4) of the phenyl ring. Whereas the formation of the 1,3-dithiolanes corresponds to a [3+2] cycloaddition of an intermediate thiocarbonyl ylide with the starting thioketone, the twelve-memberd ring has to be formed via dimerization of the ‘thiocarbonyl ylide’ with an extended biradical structure.

A series of phenyl/hetaryl and bishetaryl thioketones have been prepared via oxygen/sulfur exchange of the corresponding ketones by treatment with Lawesson’s reagent. The nonsymmetrical ketones were conveniently accessible via the reactions of lithiated furan, thiophene, and selenophene with N,N-dimethylbenzamide and hetarylcarboxamides, respectively, whereas the symmetrical ketones were obtained by treatment of ethyl N,N-dimethylcarbamate with 2 equiv of lithiated heterocycles. Under typical conditions, selected examples of the hetaryl thioketones were oxidized selectively to give thiocarbonyl S-oxides (sulfines). Reactions with diazomethane at –65°C yielded 1,3-dithiolanes in a regioselective manner and hetero-Diels–Alder reactions of 2-thienyl substituted thioketones with dimethyl acetylenedicarboxylate yielded the corresponding 7H-thieno[2,3- c]thiopyran-4,5-dicarboxylates.

The thermal reaction of trans-1-methyl-2,3-diphenylaziridine (trans-1a) with aromatic and cycloaliphatic thioketones 2 in boiling toluene yielded the corresponding cis-2,4-diphenyl-1,3-thiazolidines cis-4via conrotatory ring opening of trans-1a and a concerted [2+3]-cycloaddition of the intermediate (E,E)-configured azomethine ylide 3a (Scheme 1). The analogous reaction of cis-1a with dimethyl acetylenedicarboxylate (5) gave dimethyl trans-2,5-dihydro-1-methyl-2,5-diphenylpyrrole-3,4-dicarboxylate (trans-6) in accord with orbital-symmetry-controlled reactions (Scheme 2). On the other hand, the reactions of cis-1a and trans-1a with dimethyl dicyanofumarate (7a), as well as that of cis-1a and dimethyl dicyanomaleate (7b), led to mixtures of the same two stereoisomeric dimethyl 3,4-dicyano-1-methyl-2,5-diphenylpyrrolidine-3,4-dicarboxylates 8a and 8b (Scheme 3). This result has to be explained via a stepwise reaction mechanism, in which the intermediate zwitterions 11a and 11b equilibrate (Scheme 6). In contrast, cis-1,2,3-triphenylaziridine (cis-1b) and 7a gave only one stereoisomeric pyrrolidine-3,4-dicarboxylate 10, with the configuration expected on the basis of orbital-symmetry control, i.e., via concerted reaction steps (Scheme 10). The configuration of 8a and 10, as well as that of a derivative of 8b, were established by X-ray crystallography.

The three-component reaction of (R)- or (S)-1-phenylethylamine (6), formaldehyde, and an α-(hydroxyimino) ketone 5, i.e., 3-(hydroxyimino)butan-2-one (5a) or 2-(hydroxyimino)-1,2-diphenylethanone (5b), yields the corresponding enantiomerically pure 1-(1-phenylethyl)-1H-imidazole 3-oxide 7 in high yield (Schemes 2 and 3). The reactions are carried out either in MeOH or in AcOH. Smooth transformations of the N-oxides into optically active 1-(1-phenylethyl)-1H-imidazoles 10 and 2,3-dihydro-1-(1-phenylethyl)-1H-imidazole-2-thiones 11 are achieved by treatment of 7 with Raney-Ni and 2,2,4,4-tetramethyl-3-thioxocyclobutanone (12), respectively (Scheme 4).

A straightforward methodology for the formation of both symmetrical and non-symmetrical hetaryl thioketones is given.

The reaction of the methyl (dialkoxyphosphinyl)-dithioformates (= methyl dialkoxyphosphinecarbodithioate 1-oxides) 10 with CH2N2 at − 65° in THF yielded cycloadducts which eliminated N2 between − 40 and − 35° to give the corresponding phosphonodithioformate S-methanides ( =methylenesulfonium (dialkoxyoxidophosphino)(methylthio)methylides) 11 (Scheme 3). These reactive 1,3-dipoles were intercepted by aromatic thioketones to yield 1,3-dithiolanes. Whereas the reaction with thiobenzophenone (12b) led to the sterically more congested isomers 15 regioselectively, a mixture of both regioisomers was obtained with 9H-fluorene-9-thione (12a). Trapping of 11 with phosphono- and sulfonodithioformates led exclusively to the sterically less hindered 1,3-dithiolanes 16 and 18, respectively (Scheme 4). In addition, reactive CC dipolarophiles such as ethenetetracarbonitrile, maleic anhydride, and N-phenylmaleimide as well as the NN dipolarophile dimethyl diazenedicarboxylate were shown to be efficient interceptors of 11 (Scheme 5).

The thiocarbonyl S-methylides 3a–c, generated in situ by thermal decomposition of the corresponding 2,5-dihydro-1,3,4-thiadiazoles, undergo [3+2] cycloadditions with diphenyl trithiocarbonate (5a) to give 1,3-dithiolanes. The regioselectivity of the reaction of the cycloaliphatic dipoles 3b and 3c is reversed in comparison with that of the aromatic 3a. A mixture of both regioisomeric cycloadducts is formed in the reaction between 3b and methyl dithiobenzoate (6a), whereas only one regioisomer is obtained with thiophthalide (7). Dialkyl phosphonodithioformates 8 are shown to be efficient C=S dipolarophiles in reactions with thiocarbonyl S-methylides 3a–3d, affording 1,3-dithiolane-4-phosphonates. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

The thermal reaction of 1-substituted 2,3-diphenylaziridines 2 with thiobenzophenone (6a) and 9H-fluorene-9-thione (6b) led to the corresponding 1,3-thiazolidines (Scheme 2). Whereas the cis-disubstituted aziridines and 6a yielded only trans-2,4,5,5-tetraphenyl-1,3-thiazolidines of type 7, the analogous reaction with 6b gave a mixture of trans- and cis-2,4-diphenyl-1,3-thiazolidines 7 and 8. During chromatography on SiO2 , the trans-configured spiro[9H-fluorene-9,5'-[1,3]thiazolidines] 7c and 7d isomerized to the cis-isomers. The substituent at N(1) of the aziridine influences the reaction rate significantly, i.e., the more sterically demanding the substituent the slower the reaction. The reaction of cis-2,3-diphenylaziridines 2 with dimethyl azodicarboxylate (9) and dimethyl acetylenedicarboxylate (11) gave the trans-cycloadducts 10 and 12, respectively (Schemes 3 and 4). In the latter case, a partial dehydrogenation led to the corresponding pyrroles. Two stereoisomeric cycloadducts, 15 and 16, with a trans-relationship of the Ph groups were obtained from the reaction with dimethyl fumarate (14; Scheme 5); with dimethyl maleate (17), the expected cycloadduct 18 together with the 2,3-dihydropyrrole 19 was obtained (Scheme 6). The structures of the cycloadducts 7b, 8a, 15b, and 16b were established by X-ray crystallography.

The reaction of 2,2,4,4-tetramethyl-3-thioxocyclobutanone (1) with cis-1-alkyl-2,3-diphenylaziridines 5 in boiling toluene yielded the expected trans-configured spirocyclic 1,3-thiazolidines 6 (Scheme 1). Analogously, dimethyl trans-1-(4-methoxyphenyl)aziridine-2,3-dicarboxylate (trans-7) reacted with 1 and the corresponding dithione 2, respectively, to give spirocyclic 1,3-thiazolidine-2,4-dicarboxylates 8 (Scheme 2). However, mixtures of cis- and trans-derivatives were obtained in these cases. Unexpectedly, the reaction of 1 with dimethyl 1,3- diphenylaziridine-2,2-dicarboxylate (11) led to a mixture of the cycloadduct 13 and 5-(isopropylidene)-4-phenyl-1,3-thiazolidine-2,2-dicarboxylate (14), a formal cycloadduct of azomethine ylide 12 with dimethylthioketene (Scheme 3). The regioisomeric adduct 16 was obtained from the reaction between 2 and 11. The structures of 6b, cis-8a, cis-8b, 10, and 16 have been established by X-ray crystallography.

The reaction of 1,2-di(1-adamantyl)-2-thioxoethanone (4c) with diazomethane and 2-diazopropane yielded 2-acylthiiranes 6a and 6b, respectively, and no 1,3-oxathioles of type 7 were formed. The reaction course is explained via [2+3]-cycloaddition, elimination of N2, and 1,3-dipolar electrocyclization of the intermediate acylsubstituted thiocarbonyl ylides of type 1. The failure of the competitive 1,5-dipolar electrocyclization is a result of the sterically unfavorable conformation of 1a.

Enantiomerically pure (R)-1-(1-phenylethyl)imidazoles 4a,b can be prepared conveniently from α-(hydroxyimino)ketones 1, (R)-1-phenylethylamine and formaldehyde, followed by deoxygenation with Raney-Ni. Similarly, the reaction with (R,R)-trans-cyclohexane-1,2-diamine yields enantiomerically pure (R,R)-trans-1,1'-cyclohexane-1,2-diyl)imidazoles 4c,d. Alkylation of these imidazole derivatives with alkylbromides leads to the corresponding 3-alkylimidazolium bromides 6 and 8, respectively, which on treatment with sodium tetrafluoroborate are transformed into the corresponding tetrafluoroborates 7 and 9. Whereas some of the imidazolium salts 7 show properties of chiral ionic liquids, the bis-imidazolium tetrafluoroborates 9 are high-melting crystalline materials.

Polycyclic, nonenolizable cycloaliphatic thioketones 1a and 1b react smoothly with the lithium salt of diethyl methylphosphonate 7 in THF solution at −40°C to afford products of the carbophilic attack exclusively. Quenching of the obtained lithium thiolates with alkyl iodides yields sulfanes of type 9 or 11, respectively, in good yields. 1-Fluoro-2,4-dinitrobenzene was shown to act as an arylating agent. In the case of the “cage” thioketone 1b, the carbanion of salt 7 approaches the CS bond from the exo-side exclusively. In contrast to the parent carbonyl compounds, thioketones 1 show no tendency to undergo the conversion analogous to the Horner–Wadsworth–Emmons reaction, which would result in the formation of an olefinic product. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:182–187, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20390

The reaction of (trimethylsilyl)diazomethane with methyl (diethoxyphosphonyl)dithioformate (2), after elimination of N2 at –35°C, yields the 4,5-bis(trimethylsilyl)-1,3-dithiolane-2-phosphonate (8). This product is the result of the dimerization of the intermediate silylated thiocarbonyl ylide (4b) to give the cyclic sulfonium ylide (7), followed by the elimination of a disubstituted carbene. Trapping of the intermediate (4b) with maleimide (9), maleic anhydride (10), thiobenzophenone (11), and the phosphonylated dithioformate (2) yields the corresponding [2+3] cycloadducts (12), (13), (14b), and (18), respectively. The crystal structures of 13 and 14b have been established by X-Ray crystallography.

The [3+2]-cycloaddition of (trimethylsilyl)diazomethane (7) with 9H-fluorene-9-thione (1) at –60°C yields the spirocyclic 2,5-dihydro-5-trimethylsilyl-1,3,4-thiadiazole 10, which eliminates nitrogen at room temperature to give the 1,4-dithiane derivative 13 by dimerization of the intermediate fluorenethione (trimethylsilyl)methanide (11). This thiocarbonyl ylide can be trapped by 1 to give the 2-trimethylsilyl-1,3-dithiolane 14 via [3+2]-cycloaddition. Furthermore, the 1,3-dipole 11 undergoes successfully [3+2]-cycloadditions with the C=S group of the phosphonyldithioformate 15 as well as with the C=C dipolarophiles maleic anhydride (18a) and N-(cyclohexyl)maleimide (18b). The structures of 13 and 14 have been established by X-ray crystallography.

The reaction of 3-phenyl-1-azabicyclo[1.1.0]butane (1a) with chlorodithio-formates (5) at room temperature yielded 3-chloro-3-phenylazetidine-1-carbodithioates (6). The same products were obtained in a two-step procedure by treatment of 1a with thiophosgene to give azetidine-1-carbothioyl chloride (7a), followed by treatment with the corresponding sulfane. 3-Chloro-3-phenylazetidine-1-thiocarbamides (8) and the corresponding O-methyl 1-carbothioates (9) were prepared by the reaction of compounds (7) with amines and methanol, respectively. These reactions open a new access to derivatives of azetidine-1-carboxylic acid.

Three isocyanides containing a tertiary nitrogen atom were investigated for use as small-molecule ruthenium scavenging agents in the workup of olefin metathesis reactions. The proposed compounds are odorless, easy to obtain, and highly effective in removing metal residues, sometimes bringing the metal content below 0.0015 ppm. The most successful of the tested compounds, II, performs very well, even with challenging polar products. The performance of these scavengers is compared and contrasted with other known techniques, such as silica gel filtration and the use of self-scavenging catalysts. As a result, a new hybrid purification method is devised, which gives better results than using either a self-scavenging catalyst or a scavenger alone. Additionally, isocyanide II is shown to be a deactivating (reaction quenching) agent for olefin metathesis and superior to ethyl vinyl ether.

The reaction of 9H-fluorene-9-thione (1) with the cis- and trans-isomers of dimethyl 1-(4-methoxyphenyl)-aziridine-2,3-dicarboxylate (cis- and trans-2, resp.) in xylene at 110° yielded exclusively the spirocyclic cycloadduct with trans- and cis-configurations, respectively (trans- and cis-3, resp.; Scheme 1). Analogously, less- reactive thioketones, e.g., thiobenzophenone (5), and cis-2 reacted stereoselectively to give the corresponding trans-1,3-thiazolidine-2,4-dicarboxylate (e.g., trans-8; Scheme 2). On the other hand, the reaction of 5 and trans-2 proceeded in a nonstereoselective course to provide a mixture of trans- and cis-substituted cycloadducts. This result can be explained by an isomerization of the intermediate azomethine ylide. Dimethyl 1,3-thiazolidine-2,2-dicarboxylates 14 and 15 were formed in the thermal reaction of dimethyl aziridine-2,2-dicarboxylate 11 with aromatic thioketones (Scheme3). On treatment of 14 and 15 with Raney-Ni in refluxing EtOH, a desulfurization and ring-contraction led to the formation of azetidine-2,2-dicarboxylates 17 and 18, respectively (Scheme 4).