A new route for the synthesis of 5,6-dihydropyridin-2(1H)-ones, 2-pyridones and (4-hydroxy-2-oxopiperid-3-yl)pyridinium chlorides by intramolecular cyclization of N-3-oxoalkylchloroacetamide derivatives

Fisyuk, A. S.; Poendaev, N. V.; Bundel, Yurii G.

doi:10.1070/mc1998v008n01abeh000877

Cited by 16 publications

(5 citation statements)

References 20 publications

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“…In both cases a competing deacylation leading to the formation of the corresponding enamines 13b and 13c was observed. For enamide 14e the KOt-Bu protocol resulted in complete deacylation to 13b, the expected pyrid-2-one 15e was not detected, indicating that this method -as also concluded by Fisyuk et al for related compounds 17 -requires substituents that are able to stabilize a negative charge next to R 2 . The TMSOTf/DIPEA promoted intramolecular condensations of β-ketoenamides 14c-h are summarized in Table 2.…”

Section: Scheme 3 Preparation Of β-Ketoenamides 14a-hmentioning

confidence: 68%

Trimethylsilyl Trifluoromethanesulfonate-Promoted Cyclocondensation of β-Ketoenamides and Subsequent Nonaflation to Pyrid-2-yl and Pyrid-4-yl Nonaflates as Flexible Precursors for Polysubstituted Pyridines

2013

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The intramolecular condensation of β-ketoenamides to 2-and/or 4-pyridone derivatives using either KOt-Bu or trimethylsilyl trifluoromethanesulfonate/Hünig's base was investigated. Subsequent nonaflation of the cyclization products allowed a facile purification and further functionalization through Suzuki-Miyaura couplings leading to new highly substituted pyridine derivatives. The dependence of the regioselectivity of cyclocondensation on the structure of the β-ketoenamides is discussed.With its ubiquitous structural motif in biologically active compounds and functional materials pyridines belong without doubt to the most important heterocycles. 1 Since the early days of organic chemistry this has been motivating chemists to search for efficient methods to synthesize functionalized pyridine derivatives. 2,3 In recent years our group developed a remarkably flexible approach for the preparation of highly functionalized pyrid-4-ones 2 by a trimethylsilyl trifluoromethanesulfonate (TMSOTf)/basepromoted intramolecular condensation of β-ketoenamides 1 (Scheme 1). A mechanistic proposal for the TMSOTfpromoted cyclocondensation has previously been presented suggesting an aldol-type step of an enolate or its equivalent with the amide carbonyl group. 4 Suitable cyclization precursors can be synthesized by a three-component reaction of lithiated alkoxyallenes, nitriles, and carboxylic acids, 5 or by N-acylation of β-ketoenamines. Suitable enamines are easily accessible via amination of 1,3-diketones, 6 or by trapping the Blaise intermediate with acetic acid anhydride. 7,8 Conversion of 4-hydroxypyridines 3 (the tautomers of 2) into the corresponding nonafluorobutanesulfonates (nonaflates) 9 allows for versatile subsequent transformations through Pd-catalyzed crosscoupling reactions. 10,11 It is known that β-ketoenamides of type 5 bearing fairly acidic protons in α-position to the amide carbonyl moiety [R 6 = (het)aryl or electron-withdrawing substituents] cyclize under basic conditions to provide pyrid-2-one derivatives 6 (Scheme 2). 12, 13 We were therefore interested, if this kind of transformation would also be possible via a TMSOTf/base-promoted condensation. Furthermore, we wanted to explore the reactivity of β-ketoenamides 7 bearing two enolizable methylene groups. We envisioned that upon treatment with TMSOTf these compounds may cyclize via intermediate 8 to give pyrid-4-ones 9 (path a) as well as via 10 to give pyrid-2-ones 11 (path b).Scheme 1 Synthesis of highly functionalized pyridine derivatives via TMSOTf-promoted cyclocondensation of β-ketoenamides 1 (Nf = nonafluorobutanesulfonyl) Scheme 2 Cyclocondensation of β-ketoenamides to pyrid-2-ones 11 and/or pyrid-4-ones 9 R 1 NH O R 2 O R 3 TMSOTf/R 3 N HN R 2 O R 3 R 1 R 4 R 4 R 1 = (het)aryl, alkenyl, refs. 4, 5 and 7 2 N R 2 R 5 R 3 R 1 R 4 4 1) NfF or Nf 2 O 2) R 5 X, [Pd]

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Section: Scheme 3 Preparation Of β-Ketoenamides 14a-hmentioning

confidence: 68%

Trimethylsilyl Trifluoromethanesulfonate-Promoted Cyclocondensation of β-Ketoenamides and Subsequent Nonaflation to Pyrid-2-yl and Pyrid-4-yl Nonaflates as Flexible Precursors for Polysubstituted Pyridines

2013

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“…It is known that α-haloacetamides can be reduced in some cases when reacted with PPh 3 [ 10 ]. The interaction of compounds 1a-g with PPh 3 under heating in ethanolic or dioxane [ 11 ] solutions proceeds with low yields and in some cases is accompanied by the formation of side products. For instance, the acetal 3 has been separated as a side product by reaction of compound 1c with PPh 3 in ethanolic solution in presence of KI.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 5,6-Dihydropyridin-2(1H)-ones, 1,5,6,8,8a-Hexahydroisoquinolin-3(2H)-ones and 4a,5,6,7,8,8a-Hexahydroquinolin-2(1H)-ones by Intramolecular Wittig Reaction

Fisyuk

Poendaev

2002

Molecules

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“…Alternatively, the piperidine ring system could be assembled by cyclization of available acyclic precursors. In this manner, intramolecular cyclization of the corresponding α-functionalized N-(3-oxoalkyl)acetamides proceeding as Knoevenagel [ 3 , 4 ] or Wittig [ 5 ] reactions lead to 5,6-dihydropyridin-2(1H)-ones. To the best of our knowledge the intramolecular Darzens reaction of N-(3-oxoalkyl)chloroacetamides, which could make possible the preparation of cis -3,4-epoxypiperidin-2-ones, has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Cyclization of N-(3-Oxoalkyl)chloroacetamides Under Basic Conditions. Synthesis of cis-3,4-Epoxypiperidin-2-ones

Fisyuk¹,

Poendaev²

2002

Molecules

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A new route for the synthesis of 5,6-dihydropyridin-2(1H)-ones, 2-pyridones and (4-hydroxy-2-oxopiperid-3-yl)pyridinium chlorides by intramolecular cyclization of N-3-oxoalkylchloroacetamide derivatives

Cited by 16 publications

References 20 publications

Trimethylsilyl Trifluoromethanesulfonate-Promoted Cyclocondensation of β-Ketoenamides and Subsequent Nonaflation to Pyrid-2-yl and Pyrid-4-yl Nonaflates as Flexible Precursors for Polysubstituted Pyridines

Trimethylsilyl Trifluoromethanesulfonate-Promoted Cyclocondensation of β-Ketoenamides and Subsequent Nonaflation to Pyrid-2-yl and Pyrid-4-yl Nonaflates as Flexible Precursors for Polysubstituted Pyridines

Synthesis of 5,6-Dihydropyridin-2(1H)-ones, 1,5,6,8,8a-Hexahydroisoquinolin-3(2H)-ones and 4a,5,6,7,8,8a-Hexahydroquinolin-2(1H)-ones by Intramolecular Wittig Reaction

Cyclization of N-(3-Oxoalkyl)chloroacetamides Under Basic Conditions. Synthesis of cis-3,4-Epoxypiperidin-2-ones

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