A new class of optically active pyrrole derivatives: (3R)-3-(pyrrol-1-yl)alk-1-enes from d-α-aminoacids

Settambolo, Roberta; Guazzelli, Giuditta; Mengali, L.; Mandoli, Alessandro; Lazzaroni, Raffaello

doi:10.1016/s0957-4166(03)00524-x

Cited by 18 publications

(10 citation statements)

References 19 publications

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“…Settambolo et al [14] reported synthesis of (3R)-3-(Pyrrol-1-yl) but-1-ene (35), (3R)-4-methyl-3-(pyrrol-1-yl) pent-1-ene (36), (3R)-3-(pyrrol-1-yl) hex-1-ene (37) in high enantiomeric excess (>92%) were prepared starting from D-α-amino acids (31). The crucial steps in the synthesis, reduction (DIBAH) of the corresponding pyrrolyl esters (33) to the corresponding Figure 1 Showing the different reagents in reactants (15)(16)(17)(18) and products (20)(21)(22)(23).…”

Section: Methodsmentioning

confidence: 99%

Simple and Multi-Component Synthesis of Pyrrole Heterocycles

Dar¹,

Mir²,

Zaman³

et al. 2017

Synth Catal

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Pyrroles is the special class of heterocyclic compounds with a broad spectrum of biological activities such as anti-inflammatory, antiproliferative, antihistaminic, anti-HIV, antifungal, antihelmintic and antiviral agents. Pyrrole is a five membered ring structure, with formula C 4 H 4 NH. The heterocyclic pyrroles are the ideal building blocks for different biologically efficient molecules including porphyrins and bile pigments. Therefore researchers are synthesizing these heterocycles through multi-stepped or single stepped pathways as target structures for biological studies. In this review, different synthetic protocols/methodologies are shown in which different entry molecules are converted into pyrrole derivatives, which are important from medicinal and pharmaceutical points of view.

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Section: Methodsmentioning

confidence: 99%

Simple and Multi-Component Synthesis of Pyrrole Heterocycles

Dar¹,

Mir²,

Zaman³

et al. 2017

Synth Catal

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“…(+)-(S)-3-Pyrrol-1-ylbut-1-ene (4a) 24 According to the procedure described above, the aldehyde 3a (2. …”

Section: (+)-(S)-3-pyrrol-1-ylhex-1-ene (4c); Typical Proceduresmentioning

confidence: 99%

“…24 L-aAmino acid methyl ester hydrochlorides 1a¢-c¢ were chosen to introduce both the stereogenic center and the useful ester functionality. L-Alanine and L-valine methyl ester hydrochlorides (1a¢ and 1b¢) were commercially available.…”

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confidence: 99%

“…L-Norvaline methyl ester hydrochloride (1c¢) was prepared from the corresponding L-amino acid 1c by treatment with gaseous hydrogen chloride in methanol (98% yield). Condensation of 1a¢-c¢ with 2,5-dimethoxytetrahydrofuran, according to a well-known procedure, 24 gave the corresponding 1H-pyrrole derivatives 2a-c in good yield (70-92%) and excellent enantiomeric excess (99%). Esters 2a-c were chemoselectively transformed into aldehydes 3a-c by treatment with one molar diisobutylaluminum hydride in hexane (1.8 equiv) at -78°C; the excess of the reducing agent was destroyed with methanol, and the resulting solution was hydrolyzed with Rochelle salt, at the same temperature.…”

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confidence: 99%

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Crucial Role of β-Elimination in Determining Regio- and Chemoselectivity of the Rhodium-Catalyzed Hydroformylation of N-Allylpyrroles: A New Approach to 5,6-Dihydroindolizines

Settambolo¹

2010

Synthesis

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Rhodium-catalyzed hydroformylation of the chiral (S)-3-alkyl-3-pyrrol-1-ylprop-1-enes at 100 atmospheres total pressure and 25°C led to the preferential formation of the branched 3-alkyl-2-methyl-3-pyrrol-1-ylpropanals. At 30 atmospheres and 125°C, the linear 4-alkyl-4-pyrrol-1-ylbutanals were obtained: these aldehydes are not the final products, but evolve into more stable 5,6-dihydroindolizines, with the same optical purity as the starting olefins, via a domino cyclization-dehydration process. According to the generally accepted mechanism for rhodium-catalyzed hydroformylation, the regioselectivity, and then the final chemoselectivity, can be rationalized by taking into account that while at room temperature no b-elimination occurs, at high temperature the belimination involves the branched rhodium-alkyl intermediate only.According to the generally accepted mechanism for the rhodium-catalyzed hydroformylation of olefins, 1 metal hydride addition to the double bond to give an isomeric metal-alkyl intermediates is a key step. This step can be reversible or nonreversible, depending on the substrate nature and the reaction conditions. Under mild conditions, i.e. at room temperature, the insertion is a nonreversible step; this is very important, because the regioselectivity for the formation of the branched b and the linear l rhodium-alkyl intermediates determines the regioselectivity for the formation of the final aldehydes B and L, respectively (Scheme 1). In contrast, if the alkyl formation is reversible, the selectivity-determining step will occur later, i.e. at the stage of the addition of carbon monoxide to the tricarbonyl species to give the tetracarbonyl species, as demonstrated by theoretical calculations in the case of hydroformylation of 1,1-diphenylethene at 100°C. 2 Both electronic and steric effects determine the regioselectivity of the formation of rhodium-alkyl complexes (Figure 1). Indeed, the hydroformylation under mild conditions of vinylaromatic substrates such as styrene, 3 vinylfurans, 4 vinylthiophenes, 5 vinylpyrroles, 6 and vinylpyridines 7 always provides a large predominance of the branched isomer over the linear one (B/L = 95:5 for styrene). As far as oxygen-containing substrates are concerned, vinyl ethers provide a regioisomeric ratio B/L of ≥ 80:20. 8 Under the same conditions, alkenes with a-hydrogens (i.e., linear alk-1-enes) give the two regioisomers in an almost 1:1 molar ratio. 9 An oxygen in the b-position to the vinyl group favors the formation of the branched isomers, as observed for allyl ethyl ether (B/L = 70:30) and similar substrates. 8 The linear isomers largely predominate over the branched ones in the hydroformylation of 3-alkyl-substituted alk-1-enes (e.g., 3-methylbut-1-ene). 10

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“…For example, the recent report of the synthesis of pyrroles from the methyl esters of alanine and norvaline gave high eeÕs; however, the yields were relatively moderate ($70%). 8 In addition, the mild reaction conditions are highlighted by the fact that sensitive products, which are prone to elimination reactions such as the pyrroles obtained from serine, b-alanine and (±)-methyl 4-amino-3-hydroxybutyrate were isolated in high yield. 9 In our hands, the latter product could not be isolated under the conventional Clauson-Kaas conditions due to rapid decomposition and formation of black tarry material.…”

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confidence: 99%

A new and high yielding synthesis of unstable pyrroles via a modified Clauson-Kaas reaction

Gourlay

Molesworth

Ryan

et al. 2006

Tetrahedron Letters

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Abstract-An investigation of the reaction requirements to effect the Clauson-Kaas pyrrole synthesis led to the formulation of a new procedure that avoids the contact of pyrroles to heat or strongly acidic conditions that cause decomposition of the desired products. The procedure involves mild hydrolysis of 2,5-dimethoxytetrahydrofuran in water to the activated species 2,5-dihydroxytetrahydrofuran that reacts with primary amines in an acetate buffer at room temperature to give N-substituted pyrroles in high yield. In the case of chiral amines, pyrrole formation proceeds with no detectable epimerisation. Acid-or heat-sensitive pyrroles are also obtained in high yield and purity.

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A new class of optically active pyrrole derivatives: (3R)-3-(pyrrol-1-yl)alk-1-enes from d-α-aminoacids

Cited by 18 publications

References 19 publications

Simple and Multi-Component Synthesis of Pyrrole Heterocycles

Simple and Multi-Component Synthesis of Pyrrole Heterocycles

Crucial Role of β-Elimination in Determining Regio- and Chemoselectivity of the Rhodium-Catalyzed Hydroformylation of N-Allylpyrroles: A New Approach to 5,6-Dihydroindolizines

A new and high yielding synthesis of unstable pyrroles via a modified Clauson-Kaas reaction

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