New Synthesis of 3-Trifluoromethylpyrroles by Condensation of Mesoionic 4-Trifluoroacetyl-1,3-oxazolium-5-olates with Phosphorus Ylides

Saijo, Ryosuke; Hagimoto, Yuri; Kawase, Masami

doi:10.1021/ol1018689

Cited by 33 publications

(9 citation statements)

References 19 publications

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“…Münchnones can be prepared from N ‐monosubstituted amino acids through an acylation/cyclodehydration sequence 5. Those with electron‐withdrawing groups (EWGs) at the 4‐position can be isolated as crystalline materials and are reasonably bench‐top stable.…”

Section: Survey Of Reaction Conditions[a]mentioning

confidence: 99%

Aryne Cycloaddition with Stable Münchnones: Synthesis of 9,10‐Dihydro‐9,10‐epiminoanthracenes and Isoindoles

2013

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Arynes react with stable münchnones in a [3+2] cycloaddition/A C H T U N G T R E N N U N G [4+2] cycloreversion sequence under mild conditions. The reaction initially affords isoindoles, but in the presence of excess arynes, these isoindole intermediates readily undergo a further aryne [4+2] cycloaddition to afford 9,10-dihydro-9,10-epiminoanthracenes in good to excellent yields. Controlling the reaction conditions to stop at the isoindole stage was attempted but proved difficult and limited. This chemistry further expands aryne dipolar cycloaddition chemistry with mesoionic substrates.Recently, we have reported that the cycloaddition of arynes with sydnones affords high yields of isoindazoles. Sydnones belong to a class of structures typically referred to as mesoionic rings, or cyclic 1,3-dipoles.[2] Other than sydnone, münchnone is another representative cyclic 1,3-dipole and is isoelectronic with sydnone. Although much less stable and more difficult to prepare than sydnones, münchnones have also attracted significant attention from the synthetic community, [3] although more often they are generated in situ. With our continuing interest in aryne cycloaddition chemistry, we were encouraged to examine the largely unprecedented cycloaddition of aryne with münch-nones. We envisioned that analogous to the cycloaddition with sydnones, the same chemistry with münchnones might lead to the formation of isoindoles. [4] Münchnones can be prepared from N-monosubstituted amino acids through an acylation/cyclodehydration sequence.[5] Those with electron-withdrawing groups (EWGs) at the 4-position can be isolated as crystalline materials and are reasonably bench-top stable. By using different acyl chlorides and anhydrides, we were able to prepare a number of münchnones in good to excellent yields from sarcosine. Unfortunately, preparation of diverse substituted münchnones remains difficult to us mainly because of isolation and purification problems.It should be remembered that for aryne cycloaddition with sydnones, the presence of EWGs at the 4-position shuts down the process.[1] For münchnones, such an EWG is a must for its stability for isolation. We hoped that replacement of the nitrogen at the 2 position by a carbon would allow for a slight increase in the electron density of the ring, and hence provide the desired reactivity with arynes. Indeed, münchnone 1 a reacted smoothly with the parent benzyne generated from 2 a at room temperature to afford two products, isoindole 3 a and a 1:2 adduct, 9,10-dihydro-9,10-epiminoanthracene 4 a (Table 1, entry 1). The formation of these two products can be explained by the mechanism illustrated in Scheme 1. Thus, 3 a was first formed by a [3+ 2] cycloaddition/A C H T U N G T R E N N U N G [4+2] cycloreversion sequence, while 4 a was apparently formed by a further [4 + 2] cycloaddition of 3 a with another molecule of benzyne. The latter [4 + 2] cycloaddition is a well-documented process. [4a, 6] The ratio of 3 a:4 a depends on the reaction conditions and the stoichiomet...

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Section: Survey Of Reaction Conditions[a]mentioning

confidence: 99%

Aryne Cycloaddition with Stable Münchnones: Synthesis of 9,10‐Dihydro‐9,10‐epiminoanthracenes and Isoindoles

2013

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“…All melting points were measured on a melting apparatus with microscope and hot stage and are uncorrected. Compounds 1j, 18 2a, 19 2f, 20 2b, 21 and 2d 22 and were prepared according to the reported procedure. Phenylboronic acid and other reagents were purchased from a local company and used as received.…”

Section: Methodsmentioning

confidence: 99%

Direct Amide Formation from N-Arylglycine Ethyl Esters and Carboxylic Acids Catalysed by Phenylboronic Acid

Huang

Sha

2013

Journal of Chemical Research

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“…Fig. 1) have also been shown to react smoothly (entries [5][6][7][8], and compound 4n has been obtained as a single regioisomer in a 90% yield (entry 8). N-Substituted 2,3-dihydroquinolin-4-ones were next examined (Table 4).…”

Section: Scheme 2 Initial Results Leading To An Acridone From a β-Lamentioning

confidence: 99%

“…Quéguiner reported a process involving nucleophilic aromatic substitution to afford the benzonaphthyridinone core (Scheme 1). 4 This ring system can also be prepared from 2-(phenylamino)nicotinic acid using either the strong acid PPA 5 or microwave irradiation 6 (Scheme 2). Dibenzonaphthyridinones have also been synthesized using PPA and a high temperature.…”

Section: Figurementioning

confidence: 99%

“…4 When the nucleophile is tethered to an electrophile, the nucleophilic addition can trigger subsequent electrophilic trapping of the aryl anion, leading to a formal σ-bond cleavage. 5 Amide functionality is one such tethered nucleophile-electrophile pair, where the nitrogen and the carbonyl serve as the nucleophile and the electrophile, respectively. Although amides typically undergo simple NH arylation, 4,6 amides with more electrophilic carbonyl groups, including trifluoroacetamides, trifluoromethanesulfinamides, 7 ureas, 8 and DMF 9 have been shown to undergo carbonyl-nitrogen cleavage.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Bioactive Nitrogen-Containing Heterocycles via Aryne Methodologies

Fang¹

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subsequently reacts with another molecule of aryne to form an acridone by extrusion of a molecule of ethylene. 2,3-Dihydroquinolin-4-ones react under the same reaction conditions to afford acridones. This is the first example of ethylene extrusion in aryne chemistry. Scheme 2. The reaction of β-lactam and aryne. Chapter 4 describes a project, which was published in Organic Letters in 2010 3 and in The Journal of Organic Chemistry in 2011 (Scheme 3). 4 This project involves a rapid and efficient synthesis of 2H-indazoles using a [3 + 2] dipolar cycloaddition of sydnones and arynes. A series of 2H-indazoles have been prepared in good to excellent yields using this protocol, and subsequent Pd-catalyzed coupling reactions can be applied to the halogenated products to generate a structurally diverse library of indazoles. This methodology has been highlighted in Synfacts. 5 Scheme 3. The sydnone project. Chapter 5 describes a project soon to be submitted for publication that details a methodology for synthesizing 2H-isoindoles and 9,10-dihydro-9,10-epiminoanthracenes from arynes and münchnones (Scheme 4). 2H-Isoindoles have been generated from arynes and münchnones by a [3 + 2] dipolar cycloaddition process under very mild reaction conditions. Due to the high reactivity of 2H-isoindoles with arynes, 9,10-dihydro-9,10-epiminoanthracenes are ultimately formed in the presence of arynes in good to excellent yields. Scheme 4. The münchnone project. Synthesis of 2H-Indazoles by the [ 3 + 2 ] Dipolar Cycloaddition of Sydnones with Arynes

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New Synthesis of 3-Trifluoromethylpyrroles by Condensation of Mesoionic 4-Trifluoroacetyl-1,3-oxazolium-5-olates with Phosphorus Ylides

Cited by 33 publications

References 19 publications

Aryne Cycloaddition with Stable Münchnones: Synthesis of 9,10‐Dihydro‐9,10‐epiminoanthracenes and Isoindoles

Aryne Cycloaddition with Stable Münchnones: Synthesis of 9,10‐Dihydro‐9,10‐epiminoanthracenes and Isoindoles

Direct Amide Formation from N-Arylglycine Ethyl Esters and Carboxylic Acids Catalysed by Phenylboronic Acid

Synthesis of Bioactive Nitrogen-Containing Heterocycles via Aryne Methodologies

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