Pyrroles with pyrrole aldehydes

Aldehydes and Ketones. Pyrrole aldehydes and ketones are somewhat less reactive than the corresponding benzenoid derivatives. The aldehydes do not undergo Cannizzaro or Perkin reactions but condense with a variety of compounds that contain active methylene groups. They also react with pyrroles under acidic conditions to form dipyrryhnethenes (26). The aldehydes can be reduced to the methyl or carbinol stmctures. The ketones undergo normal carbonyl reactions. 

A-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloaddition reactions with carbonyl compounds to give oxetanes. This is illustrated by the addition of furan and benzophenone to give the oxetane (138). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 139). The intermediate oxetane undergoes rearrangement under the reaction conditions (79JOC2949). 

A two-step procedure was required for the preparation of a diverse set of pyrrole-3-carboxylic acid derivatives. The diketone 15 was prepared using a functional homologation of a 6-ketoester 14 with different aldehydes followed by oxidation with PCC. The Paal-Knorr reaction was carried out in AcOH in a sealed tube under microwave irradiation (180 °C, 5-10 min) to give differently substituted pyrroles with a COOMe group in position 3 (Scheme 5). This group was further transformed to expand the diversity of the products prepared with this method [32]. 

Redistilled N, O-persilylated L-proline 438 reacts with pivaldehyde in pentane at ambient temperature to give the 0,N-acetal 439 in 78% yield in the presence of LDA this condenses, a to the carbonyl group, with N-alkyl-2-pyrrole aldehydes [48] (Scheme 5.14). 

Boiadjiev and Lightner synthesized fluorescent tricyclic-bridged pyrrinones such as 31 by base-catalyzed condensation-cyclization of pyrrolin-2-one 112 with pyrrole aldehyde 113 (Equation 24) <2005M553, 2005JOC689>. 

The use of Pd/C to effect decarbonylation reactions, which has long been known, is equally successful with pyrrole aldehydes, e.g., 204 to 205 [108]. 

Krausz el al. have synthesised two series of amino acid porphyrinylsugar derivatives (Fig. 5). One of them involves the coupling of adequate glycoporphyrin derivatives, prepared by pyrrole/aldehyde condensation methodology, with 9-fluorenylmethoxycarbonyl-L-alanine (Fmoc-L-alanine) to give the tri-, di-, and mono-alanine glycoporphyrin derivatives 54—57 after the deprotection step the other series (58) involves a glucosylamino acid moiety instead of the alanine in their preparation.21,44... 

Pyrroles and indoles have one further unique mode of lateral lithiation—deprotonation of an Af-methyl group (also an a lithiation). The reaction works particularly weU with an aldehyde director, temporarily protected as the a-amino alkoxide 565 (Scheme 228)°° . 

The oldest methods for synthesis involve the condensation-cyclization of trifluor-omethyl or fluoroalkyl pyrroles in the presence of a metal salt. These reactions afford tetrakis(fluoroalkyl) porphyrins. The electrophilic trifluoromethylation of porphyrins is selective and leads to /I-CF3 and meso-CVT, porphyrins. While condensation of meio-trifluoromethyl-dipyrromethane with an aldehyde in acidic medium is rather difficult, it proceeds with better yields and permits a selective introduction of trifluoromethyl groups in meso The Ruppert reagent (CF3TMS) has been used to... 

The condensation reaction of some selected furo[3,2-b]pyrrole aldehydes (8g, 266,267) with benzothiazolium salts was carried out in refluxing methanol with pyridine as catalyst giving 269a-d <2004MOL241>. 

The formation of 3-pyrrolylcarbinols (280) from the photochemically induced reaction of pyrrole, or its 1-alkyl derivatives, with aliphatic aldehydes and ketones is thought to proceed via an oxetane intermediate (279) (79JOC2949). In contrast, the analogous reaction of 1 -phenylpyrrole with benzophenone leads to the formation of the diphenyl(2-pyrrolyl)car-binol, whilst the oxetane (281) has been isolated from the photoaddition of 1-benzoylpyrrole and benzophenone (76JHC1037, B-77MI30500). 2-Benzoyl-1-methylpyrrole undergoes a normal Paterno-Buchi photocyclization with 2,3-dimethylbut-2-ene, via the n -> v triplet... 

The lithium derivatives of 1-substituted pyrroles and indoles provide another general route of access to 2-acyl pyrroles and indoles. The ketones can be obtained directly by reaction with aryl nitriles or acid halides but, at least for 1-benzenesulfonylindole, a two-step procedure involving reaction with an aldehyde followed by oxidation of the carbinol to the ketone is frequently more convenient (equation 179) (73JOC3324, 75JOC2613). This method is probably the most general route to 2-acylindoles, although many have also been prepared by direct Fischer cyclization (see Section 3.06.3.4.2). 

Scheme 2 Condensation of pyrrole with mixed aldehydes (ACHO BCHO/3 l). Formation of a mixture of meso-tetraary I porphyrins (A=B =Ar).

This above result was only obtained with maleimide as the dipolarophile. With dimethyl fumarate and fumaronitrile, A2-pyrrolines are obtained, probably because of the acidity of the hydrogen atoms a- to ester and nitrile functionalities. Reaction with alkynes produces pyrrole derivatives in good to excellent yields and with aromatic aldehydes leads regioselectively to oxazolidines in moderate yields.263... 

Pyridines and pyrroles can be formed in different pathways by Mail-lard reaction. The formation of 5-methyl pyrrole aldehyde and 6-methyl-3-pyridinole has been observed by Nyhammar et al (17) by the reaction of isotope labelled 3-deoxyosone with glycine. The 3-deoxy-hexosone represents an -dicarbonyl compound and in this way the Strecker degradation occurs. Another pathway is the reaction of fu-rans with ammonia. Under roast conditions, we have obtained primarily the corresponding pyrrole, whereas we found the corresponding py-... 

Pyrrole, like thiophene, does not react with benzophenone to give the corresponding oxetane. However, pyrrole reacts with aliphatic aldehydes and ketones to the corresponding 3-pyrryl carbinols. The alcohols derive from the cleavage of the corresponding oxetanes (Scheme 3.48) [94]. The yields increase when A -methylpyrrole is used as substrate, while the reactivity is depressed in the presence of substituents on the pyrrole ring. 

A novel Mannich reaction between A -alkoxycarbonylpyrroles 739, formaldehyde, and primary amine hydrochlorides catalyzed by Y(OTf)3 gave a monoaminoalkylation product 741 some times in good yield (14-81%) in aqueous media (Scheme 146) <2001TL461>. When formaldehyde was replaced by acetaldehyde or benzaldehyde, no reaction occurred. There was no formation of the 2,7-diazabicyclo[2.2.1]hept-5-ene 740 (through the aza-Diels-Alder reaction of an N-protected pyrrole with an aldehyde and amine salts by catalysis with triflate). 

An intramolecular reaction with primary amine as the nucleophile that was prepared in situ by the reduction of the nitro group in pyrrole 1319 resulted in the pyrrolo[2,Tf]benzo[/ ]diazepine 1320, which indicates that the amino group reacts via condensation with the aldehyde group rather than via substitution of the chloro group (Equation 287) <2005T5831>. 

Benzo[i7]thiophen-3-yl)pyrrole (37) was reacted sequentially with mesityl aldehyde, DDQ and Bp3-OEt2 to afford 4,4-difluoro-3,5-di(benzo [ 7]thiophen-3-yl)-8-mesityl-4-bora-3a,4a-diaza-s-indacene (156) (Equation (46)), a representative of the novel BODIPY fluorophore family in 34% overall yield (09CEJ5823). 

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