NOTS 5097% Scheme 23 catalysed cyclisations of none p-tolylsulfonylhydrazones to Ar 1-(p-tolylsulfonylamino)aminopyrroles have been described. 6 Knight and co-workers have adapted their iodocyclisation reactions to provide routes 2, 5-disubstituted pyrroles with or ithout an iodo substituent at C-357-58 The methodology is illustrated in Scheme 20. The synthesis of methyl 2-aryl- pyrrole-3-carboxylates from methyl buta-2, 3-dienoate which is exemplified in Scheme 21 is conceptually quite different but probably involves the same kind of endo-cyclisation and induced dehydrohalogenation. s Other cyclisation reactions hat have been used for specifically substituted pyrroles include he reaction of the diene 44 with arylamines to give l-aryl l2, K CO3 2, 3, 4, 5-tetrakis( trifluoromethyl)pyrroles, the cyclisation of Meo 5-chloropent-3-en-2-one with homochiral NHTS 1-substituted 2-methylpyrroles6 and the reaction of the dienones 45 with various amines to give 1, 2, 5-trisubstituted DS ONE MO.C- Two three-component pyrrole syntheses are illustrated in cheme 2467 and in Scheme 25.6 The samarium(n) iodide catalysed condensation of alkylamines, aldehydes and nitro- alkanes gave 1, 2, 3, 4-tetrasubstituted pyrroles in moderate to methodology to construct intermediates from which 1, 2, 3- triarylpyrroles were obtained by acid catalysed cyclisation. CO Me CO Me R'NH + R2 CO,Me Scheme 24 Scheme 21 Other new cyclisation reactions in which the N-C2 bonds of pyrroles are formed are illustrated in Scheme 22and Scheme 23. I Trimethylsilyldiazomethyllithium is used to generate a vinylidene carbene 40 from which the five-membered ring is generated by intramolecular N-Hinsertion The oxime tosylate 41 probably cyclises by N-o insertion of the palladium catalyst ICO, H followed by an intramolecular Heck reaction. 2-Substituted-3- 66-74%Ph itropyrroles were isolated in good yield from the reaction of aminoacetaldehyde dimethyl acetal with B(methylthio)nitro- (Bt= benzotriazolyl alkenes 62 Scheme 25 TMSC(L)N2 C NHBn Furstner's remarkably short synthesis of the macrotricyclic core of roseophilin, a pyrrolic antitumour agent, incorporates a new and potentially more general method of synthesis of 2, 4-disubstituted pyrroles; the key steps are outlined in Scheme 26.,/ It includes the formation and reaction of tw Tt-allylpalladium intermediates A simple route to 2-(alkylthio)pyrroles is the base catalysed yclisation of allyl isothiocyanate followed by s-alkylation (Scheme 27). The use of isothiocyanate anions has been extended to the synthesis of more highly substituted 2-(alkyl Scheme 2? thio)pyrroles. A similarly mild synthesis of 2-arylpyrro is the opening of cyclopropane-1, 2-diammonium salts 47 with The aza-Wittig reaction of azido ketones 42 has been previ- aromatic aldehydes. The reactions go in buffered methanol at ously reported as a route to pyrrolines 43. These pyrrolines have room temperature and bis(alkylam n)salts can be used i now been efficiently converted into 2-aryl-3-halopyrroles by the same way bis-halogenation at C-3 with NCS or NBS followed by base B-Enaminocarbonyl compounds have been used to construct Chem Soc. perkin Trans. 1999. 2849-2866 2853J. Chem. Soc., Perkin Trans. 1, 1999, 2849–2866 2853 catalysed cyclisations of ynone p-tolylsulfonylhydrazones to 1-(p-tolylsulfonylamino)aminopyrroles have been described.56 Knight and co-workers have adapted their iodocyclisation reactions to provide routes 2,5-disubstituted pyrroles with or without an iodo substituent at C-3.57,58 The methodology is illustrated in Scheme 20.58 The synthesis of methyl 2-aryl￾pyrrole-3-carboxylates from methyl buta-2,3-dienoate which is exemplified in Scheme 21 is conceptually quite different but probably involves the same kind of endo-cyclisation and aromatisation steps.59 Other new cyclisation reactions in which the N–C2 bonds of pyrroles are formed are illustrated in Scheme 22 60 and Scheme 23.61 Trimethylsilyldiazomethyllithium is used to generate a vinylidene carbene 40 from which the five-membered ring is generated by intramolecular N–H insertion. The oxime tosylate 41 probably cyclises by N–O insertion of the palladium catalyst followed by an intramolecular Heck reaction. 2-Substituted-3- nitropyrroles were isolated in good yield from the reaction of aminoacetaldehyde dimethyl acetal with β-(methylthio)nitro￾alkenes.62 The aza-Wittig reaction of azido ketones 42 has been previ￾ously reported as a route to pyrrolines 43. These pyrrolines have now been efficiently converted into 2-aryl-3-halopyrroles by bis-halogenation at C-3 with NCS or NBS followed by base Scheme 19 Scheme 20 Scheme 21 Scheme 22 induced dehydrohalogenation.63 Other cyclisation reactions that have been used for specifically substituted pyrroles include the reaction of the diene 44 with arylamines to give 1-aryl- 2,3,4,5-tetrakis(trifluoromethyl)pyrroles,64 the cyclisation of 5-chloropent-3-en-2-one with homochiral amines to give chiral 1-substituted 2-methylpyrroles 65 and the reaction of the dienones 45 with various amines to give 1,2,5-trisubstituted pyrroles 46. 66 Two three-component pyrrole syntheses are illustrated in Scheme 24 67 and in Scheme 25.68 The samarium() iodide catalysed condensation of alkylamines, aldehydes and nitro￾alkanes gave 1,2,3,4-tetrasubstituted pyrroles in moderate to good yield. Katritzky and co-workers used benzotriazole methodology to construct intermediates from which 1,2,3- triarylpyrroles were obtained by acid catalysed cyclisation.68 Fürstner’s remarkably short synthesis of the macrotricyclic core of roseophilin, a pyrrolic antitumour agent, incorporates a new and potentially more general method of synthesis of 2,4-disubstituted pyrroles; the key steps are outlined in Scheme 26.69,70 It includes the formation and reaction of two π-allylpalladium intermediates. A simple route to 2-(alkylthio)pyrroles is the base catalysed cyclisation of allyl isothiocyanate followed by S-alkylation (Scheme 27).71,72 The use of isothiocyanate anions has been extended to the synthesis of more highly substituted 2-(alkyl￾thio)pyrroles.73 A similarly mild synthesis of 2-arylpyrroles is the opening of cyclopropane-1,2-diammonium salts 47 with aromatic aldehydes.74 The reactions go in buffered methanol at room temperature and bis(alkylammonium) salts can be used in the same way. β-Enaminocarbonyl compounds have been used to construct Scheme 23 Scheme 24 Scheme 25