Synthesis of benzyl and <i>tert</i>‐butyl 3‐(2‐methoxycarbonylethyl)‐4‐methylpyrrole‐2‐carboxylates from methyl 4‐oxobutanoate

Drinan, Martin A.; Lash, Timothy D.

doi:10.1002/jhet.5570310144

Cited by 29 publications

(9 citation statements)

References 26 publications

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“…This synthetic method to obtain 24c was simpler than the reported procedure. [84][85][86] We initially planned to prepare acid free bilin chromophores by hydrolysis of the dimethyl ester groups at the C8 and C12 positions of the chromophores. However, it was found that an exocyclic olefin at the C3 position tends to migrate to endocyclic position (C2) under basic conditions at several synthetic stages toward PCB and its derivatives.…”

Section: Synthetic Strategy Of Bilin Chromophoresmentioning

confidence: 99%

Studies on the Structure and Function of Phytochromes as Photoreceptors Based on Synthetic Organic Chemistry

Inomata

2008

Bulletin of the Chemical Society of Japan

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Section: Synthetic Strategy Of Bilin Chromophoresmentioning

confidence: 99%

Studies on the Structure and Function of Phytochromes as Photoreceptors Based on Synthetic Organic Chemistry

Inomata

2008

Bulletin of the Chemical Society of Japan

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“…The side chain was introduced by using aldehyde 22a – d as electrophile and BF 3 etherate as catalyst 11. Aldehyde 22a was obtained by using a previously described procedure,12 whereas compounds 22b – d were prepared by hydrolysis and esterification of γ‐butyrolactone followed by Swern oxidation.…”

Section: Resultsmentioning

confidence: 99%

Synthetic Strategies for the Synthesis and Transformation of Substituted Pyrrolinones as Advanced Intermediates for Rhazinilam Analogues

Kholod

Vallat²,

Buciumas³

et al. 2014

Eur J Org Chem

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The biaryl core structure of rhazinilam with its fixed dihedral angle is a pivotal element for its unique in vitro cytotoxic activity. Most of the related natural products are oxidized versions of rhazinilam. Replacing the sensitive pyrrole ring by a pyrrolinone ring is the basis of our initial strategy towards rhazinilam analogues. With this goal, variants of the sequence crossed Mukaiyama aldol reaction followed by the Staudinger reaction were studied. Reacting a suitably substituted acetophenone with O‐methyl O‐trimethylsilyl ketene acetal gave pyrrolinones 8a and 8b in good to excellent yields. These intermediates could be transformed in four high‐yielding steps into the pyrrolic precursors 7a–c containing all the atoms necessary for the construction of rings A, B, and C of rhazinilam. Our studies illustrate a lack of stability of these intermediates. Alternative synthetic approaches towards this central biaryl core structure are described.

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“…The potassium carbonate was removed by filtration and washed with chloroform (100 ml). The solvent, including excess nitromethane, was evaporated under reduced pressure to give a colorless liquid, from which 11 was obtained in 60% yield (44.1 g) as a colorless oil after distillation under reduced pressure, bp 80-82 °C at 0.5 mm Hg, (lit [15] bp 74-82°C at 0.25 mm Hg). A by-product, dimethyl 4-nitro-1,7-heptanedioate, bp 140-150 °C at 0.5 mm Hg, was isolated as a viscous oil, 26.8 g (23%).…”

Section: Methodsmentioning

confidence: 99%

An improved coupling procedure for the barton‐zard pyrrole synthesis

Bobáľ¹,

Lightner²

2001

Journal of Heterocyclic Chem

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An improved final step in the Barton-Zard pyrrole synthesis uses inexpensive potassium carbonate as base in the coupling-cyclization reaction of vic-nitro-acetates with isocyanides. In this modification the isolated yields of synthetically useful 2-carboalkoxypyrroles (1a,b and 3) and 2-(p-toluenesulfonyl)pyrroles (2a,b) consistently rise to the 78-89% range. Conversion of 2a to 5-(p-toluenesulfonyl)-2-pyrrolinone 4 is conveniently and directly achieved by reaction with 30% hydrogen peroxide in acetic acid, thus circumventing the commonly used two step procedure involving bromination followed by solvolysis.J. Heterocyclic Chem., 38, 527 (2001).Pyrrole 2-esters have been synthesized by a wide variety of methods, and with appropriate substituents and a hydrogen at C(5), they have proved to be important components in the syntheses of dipyrroles, porphyrins and their homologs, and linear oligopyrroles [1][2][3]. 5H-Pyrroles, such as 1a, 1b and 3 (Figure 1), are typically prepared from 5-methylpyrroles 5 and 6 by removal of the methyl group [4], e.g., perchlorination to trichloromethyl, then hydrolysis to a carboxylic acid followed by decarboxylation. In order to improve the yields of 5H-pyrroles formed from pyrrole 5-carboxylic acids, the latter were decarboxylated in the presence of iodine, and the resulting 5-iodo pyrroles were de-iodinated by catalytic hydrogenolysis on palladium or platinum oxide [4c,e-j]. Thus, the benzyl ester of 5 has been converted to 1a in 4 steps and an overall yield of 28% by the following transformations: (5-methyl, 2-carbobenzyloxy) → (5-carboxy, 2-carbobenzyloxy) → (5-carboethoxy, 2-carbobenzyloxy) → (5-carboethoxy, 2-carboxy) 1a [4b]. Alternatively, rather than directly decarboxylating in the final step, (5-carboethoxy, 2-carboxy) was converted to (5-carboethoxy, 2-iodo) and then to 1a in 43% overall yield [4c]. Similarly, pyrrole 5 was converted to 1b by the sequence 5 (2-carboethoxy, 5-carboxy) 1b; however, a yield was not cited [4d]. The conversion was also achieved via the iodopyrrole (2-carboethoxy, 5-iodo) in overall yields ranging from 38-49% [4e-g]. Synthesis of the more elaborate pyrrole 3 from 6 was achieved in overall yields of 43-86% by sequence: 6 (2-carbobenzyloxy, 5-carboxy) → (2-carbobenzyloxy, 5-iodo) 3, where step 1 employed sulfuryl chloride and step 2 used iodine-potassium bicarbonate [4h-j].More recently, 1a and 3 have been synthesized directly and in fewer steps by pyrrole-forming cyclizations [5][6][7], including the Barton-Zard reaction [6] of the vic-nitroacetates (7a and 8) with the required isocyanoacetate ester: 9a to give 1a [5c], 9b to give 3 [7] in the presence of tetramethylguanidine (TMG) or 1,8-diazobicyclo[5.4.0]-undec-7-ene (DBU) (Scheme 1). Although no yield was cited for 1a [5c], related cyclizations gave 38-47% yields [5a,b]. No reports have appeared for the synthesis of 1b by the Barton-Zard reaction [6]; whereas, at least four such successful attempts have been published for the synthesis of 3 all using DBU as base, and all with yields 62-73% [...

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Synthesis of benzyl and tert‐butyl 3‐(2‐methoxycarbonylethyl)‐4‐methylpyrrole‐2‐carboxylates from methyl 4‐oxobutanoate

Cited by 29 publications

References 26 publications

Studies on the Structure and Function of Phytochromes as Photoreceptors Based on Synthetic Organic Chemistry

Studies on the Structure and Function of Phytochromes as Photoreceptors Based on Synthetic Organic Chemistry

Synthetic Strategies for the Synthesis and Transformation of Substituted Pyrrolinones as Advanced Intermediates for Rhazinilam Analogues

An improved coupling procedure for the barton‐zard pyrrole synthesis

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