Pyrrole, synthesis

An interesting pyrrole synthesis is based on an application of a copper catalyzed 1,4-addition of an activated CH2 group to a conjugated ene— dizo system [89]. 

Another approach to pyrrole synthesis is based on transition metal catalyzed rearrangement of azirines [57]. 

Arizines also afford pyrrole through catalyzed cycloaddition reactions [57.  

In the past, some groups have looked at the catalytic [3-1-2] cycloaddition as a route to pyrroles. Again, the advantage is the atom-economic2il aspect of the procedure. 

The first report was made by Saikachi et al. [98] in 1979. They reacted dimethyl acetylenedicar-boxylate and methyl propiolate with /j-tosylmethyl isocyanide in the presence of DBU to give the corresponding pyrroles in low yields (7% and 12%, respectively). 

19) These molecules were of interest to us due to our research program on the synthesis of libraries of pyrrolidine analogues possessing a-glucosidase inhibitir properties [96]. 

MeOC0H4, P-CF3C0H4, isopropenyl, H,C02Et2), COMe (Ph), CONEt2 (Ph), 

In 2009, de Meijere s group reported on the formal cycloaddition of a-metallated methyl isocyanides onto the triple bond of electron-deficient acetylenes, giving oligosubstituted pyrroles. The reaction showed broad scope (24 examples, 25-97% yield). In addition, a related novel Cu(l)-mediated synthesis of 2,3-disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides was reported (11 examples, 5-88% yield) [99,100]. 

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Knoevenagel reaction Knorr pyrrole synthesis. Kolbe>Schmitt reaction Leuckart reaction Mannich reaction... 

The Piloty-Robinson pyrrole synthesis (74JOC2575,18JCS639) may be viewed as a monocyclic equivalent of the Fischer indole synthesis. The conversion of ketazines into pyrroles under strongly acidic conditions apparently proceeds through a [3,3] sigmatropic rearrange-... 

Remarkably few examples of this type of ring construction are available. The cobalt carbonyl hydride catalyzed hydroformylation of A/,A/ -diallylcarbamates has provided 3-pyrrolidinones (Scheme 61a) (81JOC4433). The pyrrole synthesis shown in Scheme 61b depends on Michael addition of ethyl a-lithioisocyanoacetate to ethyl a-isocyanocrotonate (77LA1174). 

The addition of 1,3-dicarbonyl compounds to /3-chloroazoalkenes is the basis of a pyrrole synthesis (Scheme 70a) 81TL1059). Pyrroles are also obtained by the reaction of enamines with azoalkenes (Scheme 70b) (79TL2969,81TL1475), and the copper(II) chloride catalyzed addition of 1,3-dicarbonyl compounds to arylazoalkenes (Scheme 70c) (82JOC684). 

The use of a vinylphosphonium salt as the source of the QQ fragment instead of the more commonly employed 1,2-dicarbonyl substrate is illustrated by the pyrrole synthesis in Scheme 79b (8UOC2570). A particularly interesting feature is the intramolecular Wittig reaction with an amide carbonyl group. A very useful synthesis of pyrroles depends upon the addition of the anion of p-toluenesulfonylmethyl isocyanide (TOSMIC) to a,/3-unsatur-... 

The exploration of the chemistry of azirines has led to the discovery of several pyrrole syntheses. From a mechanistic viewpoint the simplest is based upon their ability to behave as a-amino ketone equivalents in reactions analogous to the Knorr pyrrole synthesis cf. Section 3.03.3.2.2), as illustrated in Schemes 91a and 91b for reactions with carbanions. Parallel reactions with enamines or a-keto phosphorus ylides can be effected with electron-deficient 2//-azirines (Scheme 91c). Conversely, electron-rich azirines react with electron deficient alkynes (Scheme 91d). 

H-pyran synthesis from, 3, 759 bis(trimethylsiloxy) in pyrrole synthesis, 4, 333 chromene synthesis from, 3, 750 cycloaddition reactions with isocyanates, azetidin-2-ones from, 7, 261 dihydropyran synthesis from, 3, 771 fuiyl... 

Dicarbonyl compounds pyridazine synthesis from, 3, 45 pyrrole synthesis from, 4, 329 reactions... 

Ethylene, /3-(dimethylamino)-nitro-in pyrrole synthesis, 4, 334 Ethylene, dithienyl-in photochromic processes, 1, 387 Ethylene, furyl-2-nitro-dipole moments, 4, 555 Ethylene, l-(3-indolyl)-2-(pyridyl)-photocyclization, 4, 285 Ethylene, l-(2-methyl-3-indolyl)-l,2-diphenyl-synthesis, 4, 232 Ethylene, (phenylthio)-photocyclization thiophenes from, 4, 880 Ethylene carbonate C NMR, 6, 754 microwave spectroscopy, 6, 751 photochemical chlorination, 6, 769 synthesis, 6, 780 Ethylene oxide as pharmaceutical, 1, 157 thiophene synthesis from, 4, 899 Ethylene sulfate — see 2,2-dioxide under 1,3,2-Dioxathiolane... 

Furan, 2,5-dialkoxy-2-( 1 -hydroxyalkyl)-2,5-dihydro-ring expansion, 1, 425 Furan, 2,5-dialkoxytetrahydro-pyrrole synthesis from, 4, 330 Furan, 2,4-dialkyl-synthesis, 4, 661, 685 Furan, 2,5-dialkyl-... 

Imidazolium halides pyrolysis, 5, 449 Imidazolium ions acylation, 5, 402 H NMR, 5, 352 hydrogen exchange, 5, 417 nucleophilic attack, 5, 375 reactivity, 5, 375 ring opening, S, 375 Imidazolium oxides in pyrrole synthesis, 4, 344 Imidazolium perchlorate, 1,3-diphenyl-acylation, 5, 402 Imidazolium salts 1-acetyl-... 

Oxazine, dihydroin pyrrole synthesis, 4, 346 Oxazine, perhydro-polymers, 1, 291... 

Phosphonium hexafluorophosphate, benzotriazolyl-N-hydroxytris(dimethylamino)-in peptide synthesis, 5, 728 Phosphonium salts chromene synthesis from, 3, 753 reactions, 1, 531 Phosphonium salts, vinyl-in pyrrole synthesis, 4, 343 Phosphonium ylides in heterocyclic synthesis, 5, 165 Phosphoramide, triethylene-as pharmaceutical, 1, 157 Phosphoramide, triethylenethio-as pharmaceutical, 1, 157 Phosphorane, pentaphenyl-synthesis, 1, 532 Phosphoranes, 1, 527-537 Berry pseudorotation, 1, 529 bonding, 1, 528... 

Pyrrolo[3,2-6]pyrrole, N,N -dimethyl-UV spectra, 4, 1044 Pyrrolo[3,2-6]pyrrole, octahydro-synthesis, 4, 1081 Pyrrolopyrroles H NMR, 4, 1041 occurrence, 4, 1042 reactivity, 4, 1049 synthesis, 4, 1068 Pyrrolo[2,3-6]pyrroles ionization potentials, 4, 1046 synthesis, 4, 293, 1070 Pyrrolo[3,2-6]pyrroles synthesis, 6, 1009 Pyrrolo[3,2-6]pyrroles, dihydrosynthesis, 4, 1081 Pyrrolo[3,4-c]pyrroles applications, 4, 1083 Pyrroloquinolines... 

PAAL - KNORR Pyrrole Synthesis Pyrrole synthesis from 1,4-butanedlone and amines. 

The Barton-Zard (BZ) pyrrole synthesis is similar both to the van Leusen pyrrole synthesis that uses Michael acceptors and TosMlC (Section 6.7) and the Montforts pyrrole synthesis using a,P-unsaturated sulfones and alkyl a-isocyanoacetates." An alternative to the use of the reactive nitroalkenes 1 is their in situ generation from P-acetoxy nitroalkanes, which are readily prepared via the Henry reaction between an aldehyde and a nitroalkane followed by acetylation. Examples are shown later. 

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