TBDMSO TBDMSO RCHO TBDMSO PhO?s COpl PhO2S atalyst but it was subsequently found that simple protic and PhOs PhO2s Lewis acids could also be used to bring about cyclisations The dimerisation of propargylamines to under the influence of a example is shown in Scheme 30 PhOs 2 Scheme 30 EtO, C Isocyanides continue to be key intermediates in the synthesi of novel pyrroles. The Barton-Zard reaction(the base catalysed E addition of alkyl isocyanoacetates to nitroalkenes) has be used to prepare a variety of new pyrroles; in particular, Lashs COH group has made extensive use of the reaction as a route to pyrrolic intermediates for porphyrin synthesis starting fror 49 polycyclic aromatic nitro compounds. -s The fused pyrroles 52-54 are examples of compounds that have been obtained in a variety of new pyrroles. The little-used Zav yalov pyrrole s preparatively useful yields by this method. In an analogue of thesis, the cyclisation of enamino acl acids 48 to N-acetylpyrroles the Barton-Zard reaction, addition of the anions of alkyl iso- 49 with acetic anhydride and a base, has been reinvestigate cyanoacetates to a, B-unsaturated sulfones led to the formation and applied to the synthesis of some novel [cl-fused pyrroles. of a variety of unusually substituted pyrroles, including the Several new trifiuoromethylpyrroles have been prepared by a bicyclic pyrrole 56(60%)from the sulfone 55.86 Tosylmethy related base catalysed cyclisation of trifluoroacetylenamines. isocyanide(Tos MIC) has been used to make new [cJannelated involves the intermediacy of vinylogous amidinium salts. 7 pyrroles 87 and 3-arylpyrroles. By prior reaction with base and 3-Aminopyrrole-24-dicarboxylates 51 have been prepared by direct route to 2-trimethylstannylpyrroles 9 This provides the he acid catalysed cyclisation of enaminones 50"and an effi- basis for the preparation of other 2-substituted pyrroles. In a ient solid phase pyrrole synthesis is based on the condensation similar way, 3, 4-bis(trimeth hylsilyl)pyrrole can be used as a pre of resin bound enaminoamides with nitroalkenes 7y cursor of other B-substituted pyrroles; this has been prepared efficiently by 1, 3-dipolar cycloaddition of the azomethine ylide (i)POCla, CH2 Cla derived from the aziridine 57 to bis( trimethylsilyl)acetylene. 0 间BncH2CO2Et Pyrroledicarboxylic esters have been prepared by similar 1, 3- dipolar addition of benzotriazolylaziridines 58 to acetylenic 5 Indoles, indolizines and carbazoles Several useful new modifications of classical methods of indole CO2Et ROc. tion of indoles bearing oxygen substituents at NMe? avoid"abnormal"cyclisation on to the substituted carbon. A temporary tether was used in the cyclisation of the hydrazone 59: the tether was subsequently removed by reaction with sodium ethoxide to provide a route to the 7-hydroxy-4-nitro- An interesting new pyrrole synthesis was developed as part of indole. 2 A sulfonyloxy group in hydrazones 60 also directs a route to the antibiotic streptorubin B. An enyne metathesis cyclisation to give mainly 7-substituted indoles. The N-H reaction( Scheme 29)was used as the key step in constructing insertion reaction of rhodium carbenoids has been used by the pyrrolic core. Initially platinum(n) chloride was used as the Moody and Swann to construct a-arylamino ketone inter 2854 J Chem. Soc.. Perkin Trans. I.1999. 2849-28662854 J. Chem. Soc., Perkin Trans. 1, 1999, 2849–2866 a variety of new pyrroles. The little-used Zav’yalov pyrrole syn￾thesis, the cyclisation of enamino acids 48 to N-acetylpyrroles 49 with acetic anhydride and a base, has been reinvestigated and applied to the synthesis of some novel [c]-fused pyrroles.75 Several new trifluoromethylpyrroles have been prepared by a related base catalysed cyclisation of trifluoroacetylenamines.76 A synthesis of ethyl 3-arylpyrrole-2-carboxylates (Scheme 28) involves the intermediacy of vinylogous amidinium salts.77 3-Aminopyrrole-2,4-dicarboxylates 51 have been prepared by the acid catalysed cyclisation of enaminones 50 78 and an effi- cient solid phase pyrrole synthesis is based on the condensation of resin bound enaminoamides with nitroalkenes.79 An interesting new pyrrole synthesis was developed as part of a route to the antibiotic streptorubin B.80 An enyne metathesis reaction (Scheme 29) was used as the key step in constructing the pyrrolic core. Initially platinum() chloride was used as the Scheme 26 Scheme 27 Scheme 28 catalyst but it was subsequently found that simple protic and Lewis acids could also be used to bring about such cyclisations. The dimerisation of propargylamines to pyrroles proceeds under the influence of a lanthanide catalyst; an example is shown in Scheme 30.81 Isocyanides continue to be key intermediates in the synthesis of novel pyrroles. The Barton–Zard reaction (the base catalysed addition of alkyl isocyanoacetates to nitroalkenes) has been used to prepare a variety of new pyrroles; 82 in particular, Lash’s group has made extensive use of the reaction as a route to pyrrolic intermediates for porphyrin synthesis starting from polycyclic aromatic nitro compounds.83–85 The fused pyrroles 52–54 are examples of compounds that have been obtained in preparatively useful yields by this method. In an analogue of the Barton–Zard reaction, addition of the anions of alkyl iso￾cyanoacetates to α,β-unsaturated sulfones led to the formation of a variety of unusually substituted pyrroles, including the bicyclic pyrrole 56 (60%) from the sulfone 55. 86 Tosylmethyl isocyanide (TosMIC) has been used to make new [c]annelated pyrroles 87 and 3-arylpyrroles.88 By prior reaction with base and chlorotrimethylstannane, its addition to enones provided a direct route to 2-trimethylstannylpyrroles.89 This provides the basis for the preparation of other 2-substituted pyrroles. In a similar way, 3,4-bis(trimethylsilyl)pyrrole can be used as a pre￾cursor of other β-substituted pyrroles; this has been prepared efficiently by 1,3-dipolar cycloaddition of the azomethine ylide derived from the aziridine 57 to bis(trimethylsilyl)acetylene.90 Pyrroledicarboxylic esters have been prepared by similar 1,3- dipolar addition of benzotriazolylaziridines 58 to acetylenic esters.91 5 Indoles, indolizines and carbazoles Several useful new modifications of classical methods of indole synthesis have been described. Two variants of the Fischer indole cyclisation enable the method to be used for the prepar￾ation of indoles bearing oxygen substituents at C-7 and thus avoid “abnormal” cyclisation on to the substituted carbon. A temporary tether was used in the cyclisation of the hydrazone 59; the tether was subsequently removed by reaction with sodium ethoxide to provide a route to the 7-hydroxy-4-nitro￾indole.92 A sulfonyloxy group in hydrazones 60 also directs cyclisation to give mainly 7-substituted indoles.93 The N–H insertion reaction of rhodium carbenoids has been used by Moody and Swann to construct α-arylamino ketone inter￾Scheme 29 Scheme 30