Pyrrole Wittig reaction

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 simplest available derivatives of pyrrole in this sense are pyrrolines (97) which are accessible by simple intramolecular aza-Wittig reaction of iminophosphorane 96, the latter being formed by a Staudinger reaction from -y-azidoketones (95), as shown in Scheme 44. The process occurs under neutral conditions, so that once the double bond is formed, it cannot isomerize (86TL1031 87NKK1250). 

Wittig reactions with pyrrole-2-aldehyde led to the esters (79) which were cyclisized to 3a-azaazulen-4-ones (80).104,105 4-Methylene-3a-aza-azulenes (81) have been obtained from 80 with stabilized phos-phoranes.36 Reaction of dimethyl acetylenedicarboxylate with 81 could not be achieved. A similar cycloaddition was successful in the synthesis of cycl[3,3,3]azines (2) (Section V). 

Vinylpyrroles and vinylindoles are extremely sensitive to acid-catalyzed dimerization and polymerization and it is significant that much of the early research was conducted on systems which were produced in situ. Even by this approach, the dimerization of, for example, 2-(3-indolyl)propene and l-(3-indolyl)-l-phenylethylene was difficult to prevent (see the formation of 110 and 120, Section 3.05.1.2.8). Similarly, although it is possible to isolate ethyl 2-(2- and 3-indolyl)propenoates, they appear to be extremely unstable at room temperature even in the absence of acid (81UP30500) to give [ 4 + 2] cycloadducts of the type (348) (cf. 77JCS(P1)1204>. For many years simple vinylpyrroles also eluded isolation, on account of their facile acid-catalyzed polymerization. Application of the Wittig reaction, however, permits the synthesis of vinyl-pyrroles and -indoles under relatively mild and neutral conditions (see Section 3.05.2.5). In contrast, heteroarylvinyl ketones, esters, nitriles and nitro compounds, obtained by condensation of the appropriate activated methylene compound with the heteroaryl aldehydes (see Section 3.05.2.5), are thermally stable and... 

Beckmann rearrangement, 4, 292 phototransposition, 4, 204 synthesis, 4, 223 Wittig reaction, 4, 294 Wolff-Kishner reduction, 4, 291 Pyrrole, 1-acyl-barrier to rotation, 4, 193 IR spectra, 4, 21, 181 rearrangement, 4, 41 synthesis, 4, 82 thermal rearrangement, 4, 202 Pyrrole, 2-acyl-acidity, 4, 297 cleavage, 4, 289 conformation, 4, 33... 

The pyrrole 19 was made by a Friedel-Crafts reaction on the known and deactivated pyrrole 25. The COiEt group deactivates C-3 and C-5 so reaction occurs at the only unaffected position. The electron-withdrawing CC Et group also makes the pyrrole less susceptible to Lewis acid degradation (chapter 39). The Wittig reaction with the ylid from 20 went in excellent yield but... 

Exposure of the substrate 174 to dimethyl acetal of azidoacetaldehyde in the presence of TMSOTf gives the intermediate 175, which affords the pyrrole 176 under conditions of intramolecular aza-Wittig reaction (Scheme 98) <2005JOC4751>. 

Compound 1295 undergoes a smooth reaction in boiling THE to produce triphenylphosphine oxide and l-(tri-fluoromethyl)-3/f-pyrrolizines 1296 that may be considered as a product of an intramolecular Wittig reaction (Scheme 247) <2006ARK55>. The tautomeric l//-pyrrolizine 1297 was not formed. When phosphorus ylides containing the trichloromethyl group 1298 were heated in THE the expected pyrrolizine 1299 was not formed, and the 2,2,2-trichloro-l-(l//-pyrrol-2-yl)ethanone 1300, dialkyl 2-butynedioate and triphenylphosphine were obtained instead (Scheme 248). 

Taking advantage of an intramolecular Wittig reaction, the a-amidoketones 316 underwent annulation to the 3-pyrrolines 317 upon treatment with the ylide 318 <199581151>. These intermediates could be further elaborated to the pyrroles 319 by base-induced elimination of benzenesulfinic acid (Scheme 37) <2000TL8969>. It should also be mentioned that a set of unusual 3-pyrroline-2-ones have been synthesized by Ugi s four-component reactions from phenacylamine hydrochloride, cyanoacetic acid, cyclohexyl isocyanide, and aldehydes, involving final formation of the C(3)-C(4) bond <1999H(50)463>. 

Wittig methodology has been used to prepare a variety of heterocyclic species, including cyclopentenones and cyclohexenones through the intramolecular Wittig reaction of 2-oxoalkylidenetriphenylphosphoranes (52) (Scheme 14), fluor-inated butanolides and butenolides, 2,5-disubstituted-pyrroles and -pyr-rolidenes, which utilised the phosphorane 4-[ 4-methylphenyl)sulfonyl]-l-... 

Trisubstituted pyrroles are obtained in 50-l(X)% yields by the addition of open chain analogs of a Reissert compound to the vinyltriphenylphosphonium cation, with subsequent cyclization by an intramolecular Wittig reaction and base-cataly elimination of HCN (Scheme 25). ... 

Cyclo-addition [76] (nitriloxide - isoxazole alkene —> isoxazoline), 1,3-dipolar cyclo-addition (pyrrole), Ugi 4-components reaction [75], Aza-Wittig reaction, N-alkylation [77], Stille reaction [78], Heck reaction [74], Pd-cata yzed amina-tion with primary and secondary alkyl- or aryl- ... 

Acenaphthyl)imino]tributylphosphoranes, [(2-azulenyl)imino]-tributylphosphorane or [(3-indenyl)imino]tributylphosphoranes interact with substrates such as a,j9-unsaturated ketones or BrCH2C(0)Ph to give acenaphthopyridine, azulenopyridine or pyrrole derivatives. Aza-Wittig reactions of ortho(vinyl) substituted aryliminotriphenyl phosphoranes provide routes to arylquinolines or benzoxazines. 

Deprotonation of the pyrrole N—H and addition of the anion to the alkenyl phosphonium salt gives an intermediate phosphonium ylide. This ylide undergoes intramolecular Wittig reaction to give the pyrrolizine 8. See E. E. Schweizer and K. K. Light, J. Am. Chem. Soc., 86 (1964), 2963. 

---