Pyrroles from dihydrofurans

Desulfurization. A synthesis of pyrroles from phenylthio dihydrofuran derivatives is mediated by HgCh-... 

The relative importance of through-bond (hyperconjugative) and through-space (homoconjugative) interactions between the heteroatom and the double bond in 2,5-dihydro-furan, -thiophene and -pyrrole has been the subject of a CNDO/S study (76ZN(A)215). This analysis concluded that the proportion of through-space interaction increased from 19% in the dihydrofuran and 20% for dihydrothiophene to 83% for the dihydropyrrole (cf. Section 2.3.3.9). 

Bromination of pyrrole with bromine gives mainly the thermodynamically more stable 3-bromo derivative, which is produced from the 2-isomer, formed initially under kinetic control, through isomerization catalyzed by the reaction product HBr. If N-bromosuccinimide is used for bromination, no HBr is produced and the 2-isomer dominates (8IJOC222I). Bromination of furan gave cis- and frans-2,5,-dibromo-2,5-dihydrofurans (isolated as the dimethoxy derivatives) in a ratio of 3 I (67BCJ130). A spectroscopic study carried out at low temperature (- 50°C) confirmed this ratio and also showed that 20% of trans-2,3-dibro-mo-2,3-dihydrofuran was formed (75CC875). It is not known whether these adducts (which demonstrate the competition between 1,4- and 1,2-addition) are intermediates along the pathway for bromine substitution, or whether they are produced in a separate equilibrium as is the case for bromination of benzo[6]furan. 

Nina A. Nedolya was born in Irkutsk (Russia) and educated in organic chemistry at the Irkutsk State University (Diploma 1972, PhD 1982, DSc 1998). From 1995 to 1999 she was associated with Prof. L. Brandsma at the Utrecht University (The Netherlands). In 1999 she obtained her second PhD from the Utrecht University. She is presently Head of the Research Group of Chemistry of Heterocyclic Compounds at A. E. Favorsky Irkutsk Institute of Chemistry. She is the author of over 210 review articles and research papers. She is also one of the inventors for 112 patents. She is interested in the chemistry of polyfunctional unsaturated heteroatomic systems (vinyl, allenyl, and alkynyl ethers and their derivatives, linear and cyclic heteropolyenes, hetero-cumulenes), including synthesis of important heterocycles, particularly pyrroles, thiophenes, thiazoles, imidazoles, dihydrofurans, dihydropyridines, pyridines, quinolines, dihydroazepines, and azepines, based on metallated allenes or alkynes and/or heterocumulenes. 

Some typical reactions of 1,1 -difluoroethene with nucleophiles are summarized in Scheme 2.18. Alkoxides [3], trialkylsilyl anion [4], ester enolates [5], and diphenylphosphinyl anion [6] attack the gem-difluorinated carbon of 5. However, it is noteworthy that nucleophilic substitution and proton abstraction are in some cases competitive, and thus s -butyl lithium abstracts the (3 -vinylic proton predominantly to generate vinyllithium. The lithium species can be trapped with an aldehyde, providing difluoroallyl alcohol, which is then hydrolyzed to a, (3-unsaturated carboxylic ester (11) [ 7 ] (Scheme 2.19). Some synthetically useful examples are shown in Schemes 2.20 and 2.21. Tetrathiafulvalene derivative (14) is prepared from difluorinated derivative (13) [8]. An elegant intramolecular version was demonstrated by Ichikawa, which provided a range of cyclized compounds (17), including dihydrofurans, thiophenes, pyrroles, and cyclopentenes, and also corresponding benzo derivatives (20) [2]. 

For example, reaction of methoxyallene with an allyHc alcohol under palladium catalysis yielded unsymmetrical mixed acetal 22a in 74% yield (Scheme 5(a)). Treatment of 22a with 10 mol% of Grubbs second generation catalyst 3, followed by add promoted aromatization yielded fiiran 12a in 79% isolated yield for the one-pot protocol. However, the nonpolar furan products were usually contaminated with (nonpolar) phosphine residues from the catalyst, which made the purification step problematic. Therefore, it was generally advantageous to purify the dihydrofuran intermediate prior to the aromatization step. In a similar manner to furans, allyftc sulfonamide 21a was converted to the N,0-acetal 23a in 63% yield under palladium catalysis. Then RCM followed by aromatization proceeded smoothly to provide the desired N-protected pyrrole 13a in 61% yield over two steps (Scheme 5(b)). This procedure can also be applied... 

The pyrrole and carbazole compounds (105) and (106) were prepared from the dihydrofuran derivative (107) as indicated in... 

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