Synthese von 4-Benzylthio- und 4-(Arylthio)-1,3-oxazol-5(2H)-onen

Synthesis of 4-(Benzylthio)-and 4-(Arylthio)-1,3-oxazole-5(2H)-ones Following a known procedure, 4-(benzylthio)-1,3-oxazol-5(2H)-one ( 4a ) was synthesized starting from sodium cyanodithioformate ( 1 ) and cyclohexanone (Scheme 1). The structure of the intermediate 4-(benzylthio)-1,3-thiazol-5(2H)-one ( 3a ) was established by X-ray crystallography. An alternative route was developed for the synthesis of 4-(arylthio)-1,3-oxazol-5(2H)-ones which are not accessible by the former reaction. Treatment of ethyl cyanoformate ( 5 ) with a thiophenol in the presence of catalytic amounts of Et₂NH and TiCl₄, followed by addition of a ketone and BF₃.Et₂O in a one-pot-reaction, gave 4f–i in low-to-fair yields (Scheme 3). Both synthetic pathways-complementary as for benzyl–S and aryl-S derivatives–seem to be limited with respect to variation of substituents of the ketone.     

Carbenoid Reactions of Dimethyl Diazomalonate with Aromatic Thioketones and 1,3-Thiazole-5(4H)-thiones

Dimethyl diazomalonate ( 4 ) and thiobenzophenone ( 2a ) do not react in toluene even after warming to 50°. After addition of catalytic amounts of Rh₂(OAc)₄, a smooth reaction under N₂ evolution afforded a mixture of thiiranedicarboxylate 5 and (diphenylmethylidene)malonate 6 (Scheme 2). A reaction mechanism via an intermediate ‘thiocarbonyl ylide’ 7 , formed by the addition of the carbenoid species 8 to the S-atom of 2a , is plausible. Similar reactions were carried out with 9H-xanthene-9-thione ( 2b ), 9H-thioxanthene-9-thione ( 2c , Scheme 4), and 1,3-thiazole-5(4H)-thione 18 (Scheme 6). In the cases of 2b and 2c , spirocyclic 1,3-dithiolanetetracarboxylates 14a and 14b , respectively, were obtained as the third product. Reaction mechanisms for their formation are proposed in Scheme 5: S-transfer from intermediate thiirane 12 to the carbenoid species yielded thioxomalonate 15 which underwent a 1,3-dipolar cycloaddition with ‘thiocarbonyl ylide’ 16 . An alternative is the formation of ‘thiocarbonyl ylide’ 17 via carbene addition to 15 , followed by 1,3-dipolar cycloaddition with 2b and 2c , respectively.     

(Benzylthio)- und (Arylthio)-substituierte Nitril-ylide: Thermische Erzeugung und Reaktionen

Thermal Generation and Reactions of (Benzylthio)-and (Arylthio)-Substituted Nitrile Ylides Thermolysis of 4-(benzylthio)- and 4-(arylthio)-1,3-oxazol-5(2H)-ones 6 , at 110–155° in the presence of dipolarophiles with activated C≡C, C?C, C?O, C?S, and N?N bonds, led to 5-membered cyclo-adducts and CO² (cf. Schemes 3, 5-7). Heating 6a and 6c in the presence of ethyl propiolate yielded ethyl quinoline-3-carboxylate ( 19 ) and ethyl pyridine-3-carboxylate( 22 ), respectively (cf. Scheme 8). These results are rationalized on the basis of the intermediate formation of thio-substituted nitrile ylides of type 7 (cf. Scheme 2), which undergo regioselective 1,3-dipolar cycloadditions with reactive dipolarophiles. In the absence of such a dipolarophile, the nitrile ylides isomerize via a [1,4]-H shift to give 2-aza-1,3-butadienes of type 20 . The latter are trapped in a Diels-Alder reaction with ethyl propiolate (cf. Scheme 8).     

Eine überraschende Ringerweiterung von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin zu 4,5-Dihydropyridin-2(3H)-on-Derivaten

An Unexpected Ring Enlargement of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine to 4,5-Dihydropyridin-2(3H)-one Derivatives The reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1a ) and 4,4-disubstituted 2-(trifluoromethyl)-1,3-oxazol-5(4H)-ones 7 in MeCN at 70° afforded 5-(dimethylamino)-3,6-dihydropyrazin-2(1H)-ones 10 (Scheme 4), whereas no reaction could be observed between 1a and 2-allyl-4-phenyl-2-(trifluoromethyl)-1,3-oxazol-5(2H)-one ( 8a ) or 4,4-dibenzyl-2-phenyl-1,3-oxazol-5(4H)-one ( 9 ). The formation of 10 is rationalized by a mechanism via nucleophilic attack of 1a onto 7 . The failure of a reaction with 9 shows that only activated 1,3-oxazol-5(4H)-ones bearing electron-withdrawing substituents do react as electrophiles with 1a . The amino-azirine 1a and 2,4-disubstituted 1,3-oxazol-5(4H)-ones 2b – e in refluxing MeCN undergo a novel ring enlargement to 4,5-dihydropyridin-2(3H)-ones 11 (Scheme 5). Several side products were observed in these reactions. Two different reaction mechanisms for the formation of 11 are proposed: either 1a undergoes a nucleophilic addition onto the open-chain ketene tautomer of 2 (Scheme 6), or 2 reacts as CH-acidic compound (Scheme 7).     

Synthese von Trifluoromethyl-substituierten Schwefel-Heterocyclen unter Verwendung von 3,3,3-Trifluorobrenztraubensäure-Derivaten

Synthesis of Trifluoromethyl-Substituted Sulfur Heterocycles Using 3,3,3-Trifluoropyruvic-Acid Derivatives The reaction of methyl 3,3,3-trifluoropyruvate ( 1 ) with 2,5-dihydro-1,3,4-thiadiazoles 4a, b in benzene at 45° yielded the corresponding methyl 5-(trifluoromethyl)-1,3-oxathiolane-5-carboxylates 5a, b (Scheme 1) via a regioselective 1,3-dipolar cycloaddition of an intermediate ‘thiocarbonyl ylide’ of type 3 . With methyl pyruvate, 4a reacted similarly to give 6 in good yield. Methyl 2-diazo-3,3,3-trifluoropropanoate ( 2 ) and thiobenzophenone ( 7a ) in toluene underwent a reaction at 50°; the only product detected in the reaction mixture was thiirane 8a (Scheme 2). With the less reactive thiocarbonyl compounds 9H-xanthene-9-thione ( 7b ) and 9H-thioxanthene-9-thione ( 7c ) as well as with 1,3-thiazole-5(4H)-thione 12 , diazo compound 2 reacted only in the presence of catalytic amounts of Rh₂(OAc)₄. In the cases of 7a and 7b , thiiranes 8b and 8c , respectively, were the sole products (Scheme 3). The crystal struture of 8c has been established by X-ray crystallography (Fig.). In the reaction with 12 , desulfurization of the primarily formed thiirane 14 gave the methyl 3,3,3-trifluoro-2-(4,5-dihydro-1,3-thiazol-5-ylidene)propanoates (E)-and (Z)- 15 (Scheme 4). A mechanism of the Rh-catalyzed reaction via a carbene addition to the thiocarbonyl S-atom is proposed in Scheme 5.     

Bildung von 5,6-Dihydro-1,3(4H)-thiazin-4-carbonsäure-estern aus 4-Allyl-1,3-thiazol-5(4H)-onen

Formation of Methyl 5,6-Dihydro-l, 3(4H)-thiazine-4-carboxyiates from 4-Allyl-l, 3-thiazol-5(4H)-ones . The reaction of N-[1-(N, N-dimethylthiocarbamoyl)-1-methyl-3-butenyl]benzamid ( 1 ) with HCl or TsOH in MeCN or toluene yields a mixture of 4-allyl-4-methyl-2-phenyl-1,3-thiazol-5(4H)-one ( 5a ) and allyl 4-methyl-2-phenyl-1,3-thiazol-2-yl sulfide ( 11 ; Scheme 3). Most probably, the corresponding 1,3-oxazol-5(4H)-thiones B are intermediates in this reaction. With HCl in MeOH, 1 is transformed into methyl 5,6-dihydro-4,6-dimethyl-2-phenyl-1,3(4H)-thiazine-4-carboxylate ( 12a ). The same product 12a is formed on treatment of the 1,3-thiazol-5(4H)-one 5a with HCl in MeOH (Scheme 4). It is shown that the latter reaction type is common for 4-allyl-substituted 1,3-thiazol-5(4H)-ones.     

Trapping of a Thiocarbonyl Ylide with Imidazolethiones,Pyrimidinethione, and Thioamides

The reactions of 1,1,3,3-tetramethyl-8-thia-5,6-diazaspirol[3.4]oct-5-en-2-one ( 1a ) with imidazole-2-thiones 3 and pyrimidine-2(1H)-thione ( 6 ) in CHCl₃ at 40 – 50° yield 2,2,4,4-tetramethylcyclobutanone dithioacetals of type 4 and 7 , respectively, by interception of the intermediate thiocarbonyl ylide 2a (Scheme 2). Thiirane 5 is formed as a minor product by 1,3-dipolar electrocyclization of 2a . When thioacetamide ( 8a ) and thiobenzamide ( 8b ) are used as trapping reagents, the primary adduct 10 undergoes a spontaneous cyclization by intramolecular nucleophilic addition of the imino group at the carbonyl group to yield bicyclic products of type 9 . The structure of 9a has been established by X-ray crystallography.     

1,3-Oxathiole and Thiirane Derivatives from the Reactions of Azibenzil and α-diazo amides with thiocarbonyl compounds

The reactions of α-diazo ketones 1a,b with 9H-fluorene-9-thione ( 2f ) in THF at room temperature yielded the symmetrical 1,3-dithiolanes 7a,b , whereas 1b and 2,2,4,4-tetramethylcyclobutane-1,3-dithione ( 2d ) in THF at 60° led to a mixture of two stereoisomeric 1,3-oxathiole derivatives cis- and trans- 9a (Scheme 2). With 2-diazo-1,2-diphenylethanone ( 1c ), thio ketones 2a–d as well as 1,3-thiazole-5(4H)-thione 2g reacted to give 1,3-oxathiole derivatives exclusively (Schemes 3 and 4). As the reactions with 1c were more sluggish than those with 1a,b , they were catalyzed either by the addition of LiClO₄ or by Rh₂(OAc)₄. In the case of 2d in THF/LiClO₄ at room temperature, a mixture of the monoadduct 4d and the stereoisomeric bis-adducts cis- and trans- 9b was formed. Monoadduct 4d could be transformed to cis- and trans- 9b by treatment with 1c in the presence of Rh₂(OAc)₄ (Scheme 4). Xanthione ( 2e ) and 1c in THF at room temperature reacted only when catalyzed with Rh₂(OAc)₄, and, in contrast to the previous reactions, the benzoyl-substituted thiirane derivative 5a was the sole product (Scheme 4). Both types of reaction were observed with α-diazo amides 1d,e (Schemes 5–7). It is worth mentioning that formation of 1,3-oxathiole or thiirane is not only dependent on the type of the carbonyl compound 2 but also on the α-diazo amide. In the case of 1d and thioxocyclobutanone 2c in THF at room temperature, the primary cycloadduct 12 was the main product. Heating the mixture to 60°, 1,3-oxathiole 10d as well as the spirocyclic thiirane-carboxamide 11b were formed. Thiirane-carboxamides 11d–g were desulfurized with (Me₂N)₃P in THF at 60°, yielding the corresponding acrylamide derivatives (Scheme 7). All reactions are rationalized by a mechanism via initial formation of acyl-substituted thiocarbonyl ylides which undergo either a 1,5-dipolar electrocyclization to give 1,3-oxathiole derivatives or a 1,3-dipolar electrocyclization to yield thiiranes. Only in the case of the most reactive 9H-fluorene-9-thione ( 2f ) is the thiocarbonyl ylide trapped by a second molecule of 2f to give 1,3-dithiolane derivatives by a 1,3-dipolar cycloaddition.     

Sequential 1,3-Dipolar Cycloadditions in the Synthesis of Novel Tri-spiro Cyclohexanones and Piperidin-4-ones

The sequential 1,3-dipolar cycloadditions of azomethine ylide and nitrile oxide to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones and 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel tri-spiro heterocycles comprising isoxazoline, pyrrolidine and acenaphthylen-1(2H)-one rings in good yields and stereoselectivity.     

Diazo-Transfer Reaction with Diphenyl Phosphorazidate

Diphenyl phosphorazidate (DPPA) was used as the azide source in a one-pot synthesis of 2,2-disubstituted 3-amino-2H-azirines 1 (Scheme 1). The reaction with lithium enolates of amides of type 2 , bearing two substituents at C(2), proceeded smoothly in THF at 0°; keteniminium azides C and azidoenamines D are likely intermediates. Under analogous reaction conditions, DPPA and amides of type 3 with only one substituent at C(2) gave 2-diazoamides 5 in fair-to-good yield (Scheme 2). The corresponding 2-diazo derivatives 6–8 were formed in low yield by treatment of the lithium enolates of N,N-dimethyl-2-phenylacetamide, methyl 2-phenylacetate, and benzyl phenyl ketone, respectively, with DPPA. Thermolysis of 2-diazo-N-methyl-N-phenylcarboxamides 5a and 5b yielded 3-substituted 1,3-dihydro-N-methyl-2H-indol-2-ones 9a and 9b , respectively (Scheme 3). The diazo compounds 5–8 reacted with 1,3-thiazole-5 (4H)-thiones 10 and thiobenzophenone ( 13 ) to give 6-oxa-1,9-dithia-3-azaspiro[4.4]nona-2,7-dienes 11 (Scheme 4) and thiirane-2-carboxylic acid derivatives 14 (Scheme 5), respectively. In analogy to previously described reactions, a mechanism via 1,3-dipolar cycloaddition, leading to 2,5-dihydro-1,3,4-thiadiazoles, and elimination of N₂ to give the ‘thiocarbonyl ylides’ of type H or K is proposed. These dipolar intermediates with a conjugated C?O group then undergo either a 1,5-dipolar electrocyclization to give spirohetrocycles 11 or a 1,3-dipolar electrocyclization to thiiranes 14 .     

Umsetzung von Diazoessigsäure-ethylester mit 1,3-Thiazol-5(4H)-thionen

Reaction of Ethyl Diazoacetate with 1,3-Thiazole-5(4H)-thiones Reaction of ethyl diazoacetate ( 2a ) and 1,3-thiazole-5(4H)-thiones 1a,b in Et₂O at room temperature leads to a complex mixture of the products 5–9 (Scheme 2). Without solvent, 1a and 2a react to give 10a in addition to 5a–9a . In Et₂O in the presence of aniline, reaction of 1a,b with 2a affords the ethyl 1,3,4-thiadiazole-2-carboxylate 10a and 10b , respectively, as major products. The structures of the unexpected products 6a, 7a , and 10a have been established by X-ray crystallography. Ethyl 4H-1,3-thiazine-carboxylate 8b was transformed into ethyl 7H-thieno[2,3-e][1,3]thiazine-carboxylate 11 (Scheme 3) by treatment with aqueous NaOH or during chromatography. The structure of the latter has also been established by X-ray crystallography. In the presence of thiols and alcohols, the reaction of 1a and 2a yields mainly adducts of type 12 (Scheme 4), compounds 5a,7a , and 9a being by-products (Table 1). Reaction mechanisms for the formation of the isolated products are delineated in Schemes 4–7: the primary cycloadduct 3 of the diazo compound and the C?S bond of 1 undergoes a base-catalyzed ring opening of the 1,3-thiazole-ring to give 10 . In the absence of a base, elimination of N₂ yields the thiocarbonyl ylide A ′, which is trapped by nucleophiles to give 12 . Trapping of A ′, by H₂O yields 1,3-thiazole-5(4H)-one 9 and ethyl mercaptoacetate, which is also a trapping agent for A ′, yielding the diester 7 . The formation of products 6 and 8 can be explained again via trapping of thiocarbonyl ylide A ′, either by thiirane C (Scheme 6) or by 2a (Scheme 7). The latter adduct F yields 8 via a Demjanoff-Tiffeneau-type ring expansion of a 1,3-thiazole to give the 1,3-thiazine.     

Eine neue Aminoazirin-Reaktion. Bildung von 3,6-Dihydropyrazin-2(1H)-onen

A New Aminoazirine Reaction. Formation of 3,6-Dihydropyrazin-2(1H)-ones The reaction of 3-(dimethylamino)-2H-azirines 1 and 2-(trifluoromethyl)-1,3-oxazol-5(2H)-ones 5 in MeCN or THF at 50–80° leads to 5-(dimethylamino)-3,6-dihydropyrazin-2(1H)-ones 6 (Scheme 3). Reaction mechanisms for the formation of 6 are discussed: either the oxazolones 5 react as CH-acidic heterocycles with 1 (Scheme 4), or the azirines 1 undergo a nucleophilic attack onto the carbonyl group of 5 (Scheme 6). The reaction via intermediate formation of N-(trifluoroacetyl)dipeptide amide 8 (Scheme 5) is excluded.     

3-(Dimethylamino)-2,2-dimethyl-2H-azirin als α-Aminoisobuttersäure(Aib)-Äquivalent: Cyclische Depsipeptide durch direkte Amid-Cyclisierung

3-(Dimethylamino)-2,2-dimethyl-2H,-azirine as an α-Aminoisobutyric-Acid (Aib) Equivalent: Cyclic Depsipeptides via Direct Amid Cyclization In MeCN at room temperature, 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and α-hydroxycarboxylic acids react to give diamides of type 8 (Scheme 3). Selective cleavage of the terminal N,N-dimethylcarboxamide group in MeCN/H₂O leads to the corresponding carboxylic acids 13 (Scheme 4). In toluene/Ph SH , phenyl thioesters of type 11 are formed (see also Scheme 5). Starting with diamides 8 , the formation of morpholin-2,5- diones 10 has been achieved either by direct amide cyclization via intermediate 1,3-oxazol-5(4H)-ones 9 or via base-catalyzed cyclization of the phenyl thioesters 11 (Scheme 3). Reaction of carboxylic acids with 1 , followed by selective amide hydrolysis, has been used for the construction of peptides from α-hydroxy carboxylic acids and repetitive α-aminoisobutyric-acid (Aib) units (Scheme 4). Cyclization of 14a, 17a , and 20a with HCI in toluene at 100° gave the 9-, 12-, and 15-membered cyclic depsipeptides 15, 18 , and 21 , respectively.     

Reaktionen von 3-(Dimethylamino)-2H-azirinen mit 1,3-Benzoxazol-2(3H)-thion

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Benzoxazole-2(3H)-thione The reaction of 3-(dimethylamino)-2H-azirines 2 with 1,3-benzoxazole-2(3H)-thione ( 5 ), which can be considered as NH-acidic heterocycle (pK_aca. 7.3), in MeCN at room temperature, leads to 3-(2-hydroxyphenyl)-2-thiohydantoins 6 and thiourea derivatives of type 7 (Scheme 2). A reaction mechanism for the formation of the products via the crucial zwitterionic intermediate A ′ is suggested. This intermediate was trapped by methylation with Mel and hydrolysis to give 9 (Scheme 4). Under normal reaction conditions, A ′ undergoes a ring opening to B which is hydrolyzed during workup to yield 6 or rearranges to give the thiourea 7. A reasonable intermediate of the latter transformation is the isothiocyanate E (Scheme 3) which also could be trapped by morpholine. In i-PrOH at 55–65° 2a and 5 react to yield a mixture of 6a , 2-(isopropylthio)-1,3-benzoxazole ( 12 ), and the thioamide 13 (Scheme 5). A mechanism for the surprising alkylation of 5 via the intermediate 2-amino-2-alkoxyaziridine F is proposed. Again via an aziridine, e.g. H ( Scheme 6 ), the formation of 13 can be explained.     

1,5-Dipolare Elektrocyclisierung von Acyl-substituierten ‘Thiocarbonyl-yliden’ zu 1,3-Oxathiolen

1,5-Dipolar Electrocyclization of Acyl-Substituted ‘Thiocarbonyl-ylides’ to 1,3-Oxathioles The reaction of α-diazoketones 15a, b with 4,4-disubstituted 1,3-thiazole-5(4H)-thiones 6 (Scheme 3), adamantanethione ( 17 ), 2,2,4,4-tetramethyl-3-thioxocyclobutanone ( 19 ; Scheme 4), and thiobenzophenone ( 22 ; Scheme 5), respectively, at 50–90° gave the corresponding 1,3-oxathiole derivatives as the sole products in high yields. This reaction opens a convenient access to this type of five-membered heterocycles. The structures of three of the products, namely 16c, 16f , and 20b , were established by X-ray crystallography. The key-step of the proposed reaction mechanism is a 1,5-dipolar electrocyclization of an acyl-substituted ‘thiocarbonyl-ylide’ (cf. Scheme 6). The analogous reaction of 15a, b with 9H-xanthen-9-thione ( 24a ) and 9H-thioxanthen-9-thione ( 24b ) yielded α,β-unsaturated ketones of type 25 (Scheme 5). The structures of 25a and 25c were also established by X-ray crystallography. The formation of 25 proceeds via a 1,3-dipolar electrocyclization to a thiirane intermediate (Scheme 6) and desulfurization. From the reaction of 15a with 24b in THF at 50°, the intermediate 26 (Scheme 5) was isolated. In the crude mixtures of the reactions of 15a with 17 and 19 , a minor product containing a CHO group was observed by IR and NMR spectroscopy. In the case of 19 , this side product could be isolated and was characterized by X-ray crystallography to be 21 (Scheme 4). It was shown that 21 is formed – in relatively low yield – from 20a . Formally, the transformation is an oxidative cleavage of the C?C bond, but the reaction mechanism is still not known.     

Umsetzung von Di(tert-butyl)- und Diphenyldiazomethan mit 1,3-Thiazol-5(4H)-thionen: Isolierung und Kristallstruktur des primären Cycloadduktes

Reaction of Di(tert-butyl)- and Diphenyldiazomethane and 1,3-Thiazole-5(4H)-thiones: Isolation and Crystal Structure of the Primary Cycloadduct Reactions of diazo compounds with C?S bonds proceed via the formation of thiocarbonyl ylides, which, under the reaction conditions, undergo either 1,3-dipolar cycloadditions or electrocyclic ring closer to thiiranes (Scheme 1). With the sterically hindered di(tert-butyl)diazomethane ( 2c ), 1,3-thiazole-5(4H)-thiones 1 react to give spirocyclic 2,5-dihydro-1,3,4-thiadiazoles 3 (Scheme 2). These adducts are stable in solution at ?20°, and they could be isolated in crystalline form. The structure of 3c was established by X-ray crystallography. In CDCl₃ solution at room temperature, a cycloreversion occurs, and the adducts of type 3 are in an equilibrium with 1 and 2c . In contrast, the reaction of 1 with diphenyldiazomethane ( 2d ) gave spirocyclic thiiranes 4 as the only product in high yield (Scheme 3). The crystal structure of 4b was also determined by X-ray analysis. The desulfurization of compounds 4 to 4,5-dihydro-5-(diphenylmethylidene)-1,3-thiazoles 5 was achieved by treating 4 with triphenylphosphine in boiling THF. The crystal structure of 5f is shown.     

3-Alkyl-1-benzoxepin-5-on-Derivate und 2-Alkyl-1, 4-naphthochinone aus 2-Acylaryl-propargyläthern

3-Alkyl-1-benzoxepin-5-one derivatives and 2-alkyl-1,4-naphtoquinones from 2-acylaryl propargyl ethers. It was found that 3-alkyl-1-benzoxepin-5(2H)-ones of type B can be synthesized by treating 2-acylaryl propargyl ethers of type A with sodium methylsulfinyl methide (NaMSM, dimesyl sodium) (Scheme 13). Oxepinone derivatives of type B undergo ring contraction with base (also NaMSM) to yield the quinol derivatives C which, oxidize (during work-up), if R² = H, to the 1,4-naphthoquinones D (Scheme 13). The propargyl ethers used are listed in Scheme 1. The naphthalene derivatives 1 and 3 give oxepinones (E- 9 and a mixture of 14/15 respectively), whereas the expected oxepinone from 2 is transformed directly into the quinone 11 (Scheme 2, 3 and 5). Isomerizations of 2-acetylphenyl propargyl ethers ( 4, 5 and 6 ) (Schemes 6, 7 and 8) are less successful because of side reactions. If however the acetyl group is replaced by a propionyl or substituted propionyl group (as in ethers 7 and 8 ) oxepinones are obtained again in good yield (Scheme 9). The mechanistic pathway for the transformation of naphthyl propargyl ethers (and phenyl derivatives) under influence of NaMSM is shown in Scheme 10. The base-catalysed conversion of 4-phenyl-l-benzoxepin-5(2H)-one,benzo[f]furo[2,3-c](10 H)-oxepin-4-oncsand 3-methoxy-G,11- dihydro-dibenzo[b, e]loxepin-11-oneinto thc corresponding quinones has been reported [13] [20] [21]. The conversion of 2-acylaryl propargyl others via the isolable benzoxepin-5-one derivativcs or directly into the specifically substituted 1,4-naphthoquinone derivatives is of synthetic interest.     

[2+3] Cycloadditions of ‘Thiocarbonyl Ylides’ (= (Alkylidenesulfonio)methanides) and diazoalkanes with N,N′-(thiocarbonyl)diimidazole (= 1,1′-(carbonothioyl)bis[1H-imidazole])

Heating of a mixture of N,N′-(thiocarbonyl)diimidazole (= 1,1′-(carbonothioyl)bis[1H-imidazole]; 1 ) and 2,5-dihydro-1,3,4-thiadiazole 2a or 2b gave the 1,3-dithiolanes 4a and 4b , respectively, via a regiospecific 1,3-dipolar cycloaddition of the corresponding ‘thiocarbonyl methanides’ 3a , b onto the C?S group of 1 (Schemes 1 and 2). The adamantane derivative 4b was not stable in the presence of 1H-imidazole and during chromatographic workup. The isolated 1,3-dithiole 5 is the product of a base-catalyzed elimination of 1H-imidazole from the initial cycloadduct 4b . The formation of the S,N-acetal 6 can be rationalized by a protonation of the ‘thiocarbonyl ylide’ 3b followed by a nucleophilic addition of 1H-imidazole. With the diazo compounds 8a–e (Scheme 3) 1 underwent a regiospecific 1,3-dipolar cycloaddition to give the corresponding 2,5-dihydro-1,3,4-thiadiazole derivatives 9 , which spontaneously eliminated 1H-imidazole to yield (1H-imidazol-1-yl)-1,3,4-thiadiazoles 10 . The structures of 10a and 10d were established by X-ray crystallography. In the case of diazodiphenylmethane ( 8f ), the initial cycloadduct 9f decomposed via a ‘twofold extrusion’ of N₂ and S to give 1,1′-(2,2-diphenylethenylidene)bis[1H-imidazole] ( 11 ; Scheme 3).     

Sacrificial azomethine ylide cycloaddition controlled chemoselective nitrile oxide cycloaddition to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: formation of mono-spiro-isoxazolines

The 1,3-dipolar cycloaddition of an azomethine ylide to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrrolidines in good yields. Further cycloaddition of these spiro-pyrrolidines with nitrile oxide afforded mono-spiro-isoxazolines in moderate yields (45-56%), presumably via a di-spiro intermediate, which undergoes a spontaneous cycloreversion of the spiro-pyrrolidine unit. In contrast, the direct cycloaddition of nitrile oxide to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones gave the mono-spiro-isoxazoline as the minor product, while the bis-spiro-isoxazolines are formed predominantly.     

N-(1,3-Thiazol-5(4H)-yliden)amine aus 1,3-dipolaren Cycloadditionen von Aziden mit 1,3-Thiazol-5(4H)-thionen

N-(1,3-Thiazol-5(4H)-ylidene)amines via 1,3-Dipolar Cycloaddition of Azides and 1,3-Thiazol-5(4H)-thiones Organic azides 5 and 4,4-dimethyl-2-phenyl-1,3-thiazol-5(4H)-thione ( 2 ) in toluene at 90° react to give the corresponding N-(1,3-thiazol-5(4H)-ylidene)amines (= 1,3-thiazol-5(4H)-imines) 6 in good yield (Table). A reaction mechanism for the formation of these scarcely investigated thiazole derivatives is formulated in Scheme 3: 1,3-Dipolar azide cycloaddition onto the C?S group of 2 leads to the 1:1 adduct C . Successive elimination of N₂ and S yields 6 , probably via an intermediate thiaziridine E .