Pyrrole-2-carbaldehyde synthesis

Mikhaleva, A.I., A.V. Ivanov, L.V. Skital tseva et al. 2009. An efficient route to 1-vinyl-pyrrole-2-carbaldehydes. Synthesis 4 587-590. 

An efficient synthesis of rigid tricyclic (5 5 5) nitrogen heterocycles 64 has been achieved via sequential and tandem Ugi/intramolecular Diels-Alder (IMDA) cycloaddition of pyrrole derivatives <2004JOC1207> and the trienes 477 were prepared by the acylaton of amines 475 with the anhydride 476. The amines 475 were in turn prepared starting from pyrrole-2-carbaldehyde. The triene 477 on heating in toluene at 80 °C for 15 h underwent the IMDA to afford the tricyclic compound 64 as a single diastereomer in quantitative yield. The sterically bulky N-substitutent on the triene 477 promoted cycloaddition under milder condition at 65 °C in toluene to provide the tricyclic compound 64 in quantitative yield (Scheme 108). 

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-f]pyrrole ring system 387 <2003T1477> and its derivatives was accomplished using the same synthetic sequence (Scheme 42). Starting with 2-methyl-benzo[ ]thiophene-3-carbaldehyde 388, an intermediate 389 was obtained. Treatment of bromo compound 389 with sodium azide in ethanol led to the stable triazoline 390. 1,3-Dipolar cycloreversion of 390 was induced by a catalytic amount of />-TsOH to give the parent 2//-benzo[4,5]thieno[2,3-c]pyrrole 387. Alternatively, direct treatment of bromo compound 389 with excess ammonia furnished 387 in one step. Compound 387 was treated with di-/-butyl dicarbonate and 4-dimethylaminopyridine (DMAP) to give iV-BOC derivative 391. Reaction of 389 with... 

Iodo-li/-pyrrole-2-carbaldehyde, used in the synthesis of nucleoside derivatives, was prepared via protection of the aldehyde group in l//-pyrrole-2-carbaldehyde with an iminium salt for the efficient w f -directed electrophilic substitution of the starting pyrrole followed by a treatment of the iminium salt with N-iodosuccinimide in acetonitrile then with sodium bicarbonate (57% two-step total yield) <2003BML4515>. 

Synthesis of 2-[5-(l//-pyrrol-2-yl)-2-thienyl]-l//-pyrrole 1355, monomer for polyconjugated polymers, is based on the reaction of l,4-di(l//-pyrrol-2-yl)-l,4-butanedione 1354 with Lawesson s reagent (Equation 292) <1997CM2876>. Compound 1356 was prepared by Triton B-catalyzed condensation of 17/-pyrrole-2-carbaldehyde and the appropriate nitrile derivative (Equation 293). 

The recently reported dilithiation of the azafulvene dimer (20) is the key step in a synthesis of 5-sub-stituted pyrrole-2-carbaldehydes. This synthesis offers a reasonable alternative to the Vilsmeier-Haack formylation for the synthesis of such compounds. An example is shown in Scheme 26. 

More promising results came from the reaction of 2-chloro-l-(methoxymethyl) indole-3-carbaldehyde (63) with a variety of nucleophiles, including pyrrole, indole, and imidazole. This chemistry was used for the synthesis of the unusual Trp-His fragment of Moroidin (65) [32]. Moreover, 2,5-dichloroindole-3-sulfone also undergoes nucleophilic replacement of the chlorine atom with imidazole to form a bioesteric analog (67) of L-737,126 (not shown), which inhibits HIV-1 reverse transcriptase [33]. 

Chiral Homo-Quadridentate Ligands. Chiral porphirines (PORPH) com-plexed to manganese(III) have been published recently as efficient epoxidation catalysts (97). The synthesis of the ligand is based on the condensation of enan-tiomerically pure [2.2]-p-cyclophane-4-carbaldehyde and pyrrol (Fig. 11). 

Another example deals with the direct synthesis of pyr-rol-2-carbaldehydes 598 and 601 to avoid installation of these moieties into preformed pyrroles. Therefore, it is necessary to change from a normal p-ketocarbonyl compound to a stabilized ketonitrile 596 to ensure only one possible reaction pathway toward the enamine (Scheme 13.150) [270]. 

Kathiravan and Raghxmathan reported the synthesis of pyrrole-fused polycyclic heterocycles via intramolecular 1,3-dipolar cycloaddition reaction of azomethine ylides derived from pyrrole-2-carbaldehyde 28 and secondary amino acids in IL [BM1M][BF4]. The methodology involved the synthesis of N-alkenyl carboxaldehyde from 28 followed by freafment with sarcosine in [BM1M][BF4] as reaction medium at 85-95 C for about 3h to afford pyrrolo-pyrrolidines 29 in good yield (Scheme 3). The same reaction when carried out in organic solvents such as toluene, methanol, and acetonitrile, the reactions observed were slow, giving product in low yield [80]. 

SCHEME 2.143 Synthesis of di(pyrrolyl)-dihydroimidazobenzimidazoles by oxidative aromatization of the Schiff bases, derivatives of pyrrole-2-carbaldehydes. 

Such stabilization is characteristic of pyrrole-2-carbaldehyde oximes and does not occur in other aromatic and aliphatic oximes. The stereospeciflc facile transformation of E-ZZ-isomer mixtures to pure salts of Z-isomer is the first known method for the synthesis of individual Z-isomers of aldoxime salts. 

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