Transacylation of α-Aryl-β-keto Esters

Nishiwaki, Nagatoshi; Nishida, Daisei; Ohnishi, T.; Hidaka, Fumie; Shimizu, Satoru; Tamura, Mina; Hori, Koichi; Tohda, Yasuo; Ariga, Masahiro

doi:10.1021/jo0344642

Cited by 22 publications

(20 citation statements)

References 22 publications

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“…Butylamine (2b) reacted in a similar manner with the keto nitrile 7 ( Table 1, run 2), however, bulkier amines such as isopropylamine (2c), tert-butylamine (2d), aniline (2e), and dipropylamine (2f) did not cause the cyclization (runs [3][4][5][6]. The high sensitivity to steric hindrance is likely due to the congestion around the reaction site of the intimate pair 11.…”

Section: A) Synthesis Of Vicinally Functionalized 14-dihydropyridinesmentioning

confidence: 99%

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Synthesis of vicinally functionalized 1,4-dihydropyridines and diazabicycles via a pseudo-intramolecular process

et al. 2014

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An α-nitro-δ-keto nitrile readily forms the corresponding ammonium salt immediately upon treatment with an amine. When the amine liberated under equilibrium, the nucleophilic amine and the electrophilic keto nitrile come close to each other to afford so-called an intimate pair. The spatial proximity realized an efficient reaction to give a 2-amino-3-nitro-1,4-dihydropyridine; the reaction proceeded like an intramolecular reaction although it is actually an intermolecular reaction, namely the pseudo-intramolecular reaction. The bifunctionality of the keto nitrile also enabled the pseudo-intramolecular imination followed by tandem cyclization leading to diazabicyclic frameworks.

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Section: A) Synthesis Of Vicinally Functionalized 14-dihydropyridinesmentioning

confidence: 99%

“…[3][4][5] In these reactions, the highly acidic keto ester reacted with the amine to form the corresponding ammonium salt 3 immediately. Then, under equilibrium, the electrophilic keto ester and the nucleophilic amine were regenerated simultaneously in close proximity.…”

Section: Scheme 1 the Concept Of The Pseudo-intramolecular Processmentioning

confidence: 99%

Synthesis of vicinally functionalized 1,4-dihydropyridines and diazabicycles via a pseudo-intramolecular process

et al. 2014

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“…The nitro group at the 3-position seems to activate the diester function at the vicinal position, however, no reasonable explanation has been given for the different reactivity between dimethyl and diethyl esters. Meanwhile, the acyl group of β-keto ester is considerably activated by a quinolyl group at the α-position, [ 18 ] and similar activation is achieved by a benzene ring ( Scheme 10 ) [ 39 ]. Thus, the bulkiness of the MeQone ring is considered to be an influential factor (See also Section 4.3 ).…”

Section: Reactivity Of Nitroquinolonesmentioning

confidence: 99%

“…While the β-diketone is converted to a pyrazole upon treatment with methylhydrazine at room temperature, deacylation proceeds under the same conditions in the case of β-keto esters ( Scheme 14 ). However, it is not necessary to employ the quinolyl group for activating the acyl group of β-keto ester because introduction of a phenyl group results in the similar activation [ 39 ]. Thus, the activation of an acyl group is not chemistry specific to MeQones.…”

Section: Unusual Reactivity Of 1-methyl-368-trinitroquinolone (Tmentioning

confidence: 99%

Chemistry of Nitroquinolones and Synthetic Application to Unnatural 1-Methyl-2-quinolone Derivatives

Nishiwaki

2010

Molecules

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The 1-methyl-2-quinolone (MeQone) framework is often found in alkaloids and recently attention was drawn to unnatural MeQone derivatives with the aim of finding new biologically active compounds, however, low reactivity of the MeQone framework prevents the syntheses of versatile derivatives. A nitro group is one of the useful activating groups for this framework that enables a concise chemical transformation. Among nitroquinolones, 1-methyl-3,6,8-trinitro-2-quinolone (TNQ) exhibits unusual reactivity favoring region-selective cine-substitutions that afford 4-substituted 1-methyl-6,8-dinitro-2-quinolones upon treatment with nucleophilic reagents. Contrary to this, 1-methyl-3,6-dinitro-2-quinolone (3,6-DNQ) does not undergo any reaction under the same conditions. The unusual reactivity of TNQ is caused by steric repulsion between the methyl group at the 1-position and the nitro group at the 8-position, which distorts the MeQone framework. As a result, the pyridone ring of TNQ loses aromaticity and acts rather as an activated nitroalkene. Indeed, the pyridone moiety of TNQ undergoes cycloaddition with electron-rich alkenes or dienes under mild conditions, whereby a new fused ring is constructed on the [c]-face of the MeQone. Consequently, TNQ can be used as a new scaffold leading to versatile unnatural MeQone derivatives.

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“…Meanwhile, we previously disclosed several efficient reactions, that proceed in a similar manner to an intramolecular reaction, even in the absence of additives . Of these reactions, transacylation is illustrated in Scheme .…”

Section: Introductionmentioning

confidence: 99%

Metal‐Free O‐Selective Direct Acylation of Amino Alcohols Through Pseudo‐Intramolecular Process

et al. 2019

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Efficient α‐aryl‐β‐keto ester acylation of amine accompanied by the elimination of ethyl phenylacetate was achieved owing to the pseudo‐intramolecular process. The eliminated ethyl phenylacetate could be recycled by conversion into an α‐aryl‐β‐keto ester upon treatment with an acyl chloride in the presence of lithium bis(trimethylsilyl)amide, by which the atom economy considerably increased. Acylation using an α‐aryl‐β‐keto ester is highly sensitive to the bulkiness of the nucleophile, which facilitated the regioselective‐acylation of the less hindered amino group in diamine without protecting the other. The transacylation of α‐aryl‐β‐keto ester with N‐alkylamino alcohol resulted in chemoselective O‐acylation without protecting the amino group because the hydroxy group was attracted to the reaction site of the keto ester by forming an ammonium salt. Transacylation was demonstrated to be a practically useful tool for organic synthesis because this protocol can be conducted under mild conditions with simple manipulations in the absence of any additives such as metal catalyst and base.

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Transacylation of α-Aryl-β-keto Esters

Cited by 22 publications

References 22 publications

Synthesis of vicinally functionalized 1,4-dihydropyridines and diazabicycles via a pseudo-intramolecular process

Synthesis of vicinally functionalized 1,4-dihydropyridines and diazabicycles via a pseudo-intramolecular process

Chemistry of Nitroquinolones and Synthetic Application to Unnatural 1-Methyl-2-quinolone Derivatives

Metal‐Free O‐Selective Direct Acylation of Amino Alcohols Through Pseudo‐Intramolecular Process

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