Details have been published of the remarkably efficient syn- In a continuation of their work on benzo[c]thiophenes, Cava thesis of 3, 4-bis(trimethylsilyl)thiophene by the high temper- and his group have described a synthesis of the bis(2-thienyl)- ature Diels-Alder addition of bis(trimethylsilyl)acetylene benzo[c]thiophene 36 from the phthalide 37. They have also 4-phenylthiazole. The thiophene can be prepared in batches described a much improved synthesis of naphtho[2, 3-c]thio- of up to 8g by this method, which has also been extended phene 38 which makes use of a base catalysed Pummerer to some other 3, 4-disubstituted thiophenes. " A 1, 3-dipolar reaction. cycloaddition approach was also investigated (Scheme 14) but was less efficient. Experimental details have als provided for the preparation of 3, 4-disubstituted thiophenes from the diketones 30 by reductive cyclisation using titanium reagents. Thiophenes bearing bulky substituents(tert-butyl 1-adamantyl, etc. ) have been prepared by this route. TMSS TMS HMPA100°C TMS--MS DDQ 15 Scheme 14 A review of routes to arylpyrroles covers both classical and Two new thiophene syntheses have been described that make recent methods, with particular emphasis on the Trofimov use of the methodology previously developed for the prepar- synthesis from aryl ketoximes and acetylenes. Several useful ation of other heterocycles. Marson and Campbell have applied variants of classical methods have been reported. The optimum a synthesis of furans, based on the ring expansion of function- conditions for the preparation of l-benzylpyrroles from ed epoxides, to analogous episulfides; for example, the benzylamines and 2, 5-dimethoxytetrahydrofuran require the episulfide 31 gave the thiophene-2-methanol 32(80%) when use of a mixture of pyridine and acetic acid as solvent. This treated with a catalytic amount of mercury(u) oxide in dilute ynthetic method has also been adapted to provide a route to sulfuric acid at room temperature. a-Fluoroalkylcarbonyl 3, 4-dialkoxypyrroles 0 5-Trifluoromethylpyrroles have been compounds 33, which have previously been used in the syn- prepared by a modified Hantzsch synthesis(Scheme 17)in thesis of fluoroalkyl substituted pyrazoles and pyrimidines, which the use of preformed enamines avoids the side reaction gave 2(a-fluoroalkyl)thiophenes on reaction with methyl that leads to furans. I The use of organotin enamines, which are mercaptoacetate and sodium methoxide( Scheme 15). table enough to be isolated and stored, also leads to pyrroles in high yields. The products of Knorr-type reductive con sensation of 1, 3-diketones with oximinocyanoacetate esters r aque solvent(Scheme 18).>Glyoxal monophenylhydrazone has been used in Knorr-type condensations with B-keto esters to give 1, 2,3,4-tetrasubstituted pyrroles. Atmospheric nitrogen has been used for the first time in place of the usual ammonia in the synthesis of pyrroles from 1, 4-dicarbonyl compounds: the reaction involves the reduction of nitrogen by a mixture of titanium(Iv) chloride, chlorotrimethylsilane and lithium R, HS CO2Me 54-76% Meo2c metal.5 33(X=F or Br Relatively few new routes to benzothiophenes have been 0-71%F2C described in the period under review. The route to benzofurans described by Katritzky and co-workers has also been used as a Scheme 17 one pot synthesis of benzothiophenes, the thioethers analogous to 24 being intermediates.36-Hydroxybenzothiophenes have been synthesised by a procedure in which the benzene ring is annelated to a 2-substituted thiophene by acid catalysed cyclis- ation."4-Chloro-1, 2, 3-dithiazole-5-thione, which is readily prepared from 4, 5-dichlorodithiazolium chloride(Appel's salt) Scheme 18 Some cyclisation reactions that were previously used to syn- lesise furans have been successfully adapted to the preparation of pyrroles. Thus, the imines 39, which are formed from the cyclise to pyrroles(Scheme 19). Some related palladium 2852 J. Chem. Soc. Perkin Trans. 11999. 2849-28662852 J. Chem. Soc., Perkin Trans. 1, 1999, 2849–2866 Details have been published of the remarkably efficient syn￾thesis of 3,4-bis(trimethylsilyl)thiophene by the high temper￾ature Diels–Alder addition of bis(trimethylsilyl)acetylene to 4-phenylthiazole. The thiophene can be prepared in batches of up to 8 g by this method, which has also been extended to some other 3,4-disubstituted thiophenes.40 A 1,3-dipolar cycloaddition approach was also investigated (Scheme 14) but was less efficient. Experimental details have also been provided for the preparation of 3,4-disubstituted thiophenes from the diketones 30 by reductive cyclisation using titanium reagents.41 Thiophenes bearing bulky substituents (tert-butyl, 1-adamantyl, etc.) have been prepared by this route. Two new thiophene syntheses have been described that make use of the methodology previously developed for the prepar￾ation of other heterocycles. Marson and Campbell have applied a synthesis of furans, based on the ring expansion of function￾alised epoxides, to analogous episulfides; for example, the episulfide 31 gave the thiophene-2-methanol 32 (80%) when treated with a catalytic amount of mercury() oxide in dilute sulfuric acid at room temperature.42 α-Fluoroalkylcarbonyl compounds 33, which have previously been used in the syn￾thesis of fluoroalkyl substituted pyrazoles and pyrimidines, gave 2-(α-fluoroalkyl)thiophenes on reaction with methyl mercaptoacetate and sodium methoxide (Scheme 15).43 Relatively few new routes to benzothiophenes have been described in the period under review. The route to benzofurans described by Katritzky and co-workers has also been used as a one pot synthesis of benzothiophenes, the thioethers analogous to 24 being intermediates.31 6-Hydroxybenzothiophenes have been synthesised by a procedure in which the benzene ring is annelated to a 2-substituted thiophene by acid catalysed cyclis￾ation.44 4-Chloro-1,2,3-dithiazole-5-thione, which is readily prepared from 4,5-dichlorodithiazolium chloride (Appel’s salt) and hydrogen sulfide, reacts with diphenyldiazomethane to give the benzothiophene 35 by way of the isolable intermediate 34 (Scheme 16).45 Scheme 14 Scheme 15 Scheme 16 In a continuation of their work on benzo[c]thiophenes, Cava and his group have described a synthesis of the bis(2-thienyl)- benzo[c]thiophene 36 from the phthalide 37. 46 They have also described a much improved synthesis of naphtho[2,3-c]thio￾phene 38 which makes use of a base catalysed Pummerer reaction.47 4 Pyrroles A review of routes to arylpyrroles covers both classical and recent methods, with particular emphasis on the Trofimov synthesis from aryl ketoximes and acetylenes.48 Several useful variants of classical methods have been reported. The optimum conditions for the preparation of 1-benzylpyrroles from benzylamines and 2,5-dimethoxytetrahydrofuran require the use of a mixture of pyridine and acetic acid as solvent.49 This synthetic method has also been adapted to provide a route to 3,4-dialkoxypyrroles.50 5-Trifluoromethylpyrroles have been prepared by a modified Hantzsch synthesis (Scheme 17) in which the use of preformed enamines avoids the side reaction that leads to furans.51 The use of organotin enamines, which are stable enough to be isolated and stored, also leads to pyrroles in high yields.52 The products of Knorr-type reductive con￾densation of 1,3-diketones with oximinocyanoacetate esters depend on whether dry or aqueous acetic acid is used as the solvent (Scheme 18).53 Glyoxal monophenylhydrazone has been used in Knorr-type condensations with β-keto esters to give 1,2,3,4-tetrasubstituted pyrroles.54 Atmospheric nitrogen has been used for the first time in place of the usual ammonia in the synthesis of pyrroles from 1,4-dicarbonyl compounds: the reaction involves the reduction of nitrogen by a mixture of titanium() chloride, chlorotrimethylsilane and lithium metal.55 Some cyclisation reactions that were previously used to syn￾thesise furans have been successfully adapted to the preparation of pyrroles. Thus, the imines 39, which are formed from the corresponding ketones and primary amines, spontaneously cyclise to pyrroles (Scheme 19).6 Some related palladium Scheme 17 Scheme 18