Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines

Nadiia V. Pikun; Natalya P. Kolesnyk; Eduard B. Rusanov; Aiva Plotniece; Martins Rucins; Arkadij Sobolev; Yuriy G. Shermolovich

doi:10.1016/j.tet.2018.04.075

Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines

Nadiia V. Pikun, Natalya P. Kolesnyk, Eduard B. Rusanov, Aiva Plotniece, Martins Rucins, Arkadij Sobolev, Yuriy G. Shermolovich (Corresponding Author)

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Electrophilic fluorination of Hantzsch-type 1,4-dihydropyridines with Selectfluor^® led to the formation of new fluorinated 2,6-heptanediones - dialkyl 2,4-diacetyl-2,4-difluoro-3-phenylpentanedioates. Novel 2,6-heptanedione derivatives in reaction with hydrazine hydrate easily form 6-amino-4,7-difluoro-3-hydroxy-1,3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octanes instead of the corresponding diazepine derivatives. The obtained 2-оxa-6-azabicyclo[2,2,2]octanes are thermally stable at the temperatures below 50°С. At higher temperatures rearrangement of 2-oxa-6-azabicyclo[2,2,2]octanes offers new fluorine-containing pyrazolinone derivatives - alkyl esters of 2-fluoro-2-((4-fluoro-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)-3-oxobutanoates.

Original language	English
Pages (from-to)	2884-2890
Number of pages	7
Journal	Tetrahedron
Volume	74
Issue number	23
DOIs	https://doi.org/10.1016/j.tet.2018.04.075
Publication status	Published - 7 Jun 2018
Externally published	Yes

Keywords*

1,4-Dihydropyridines
2,4-Diacetyl-2,4-difluoro-3-phenylpentanedioates
2-Oxa-6-azabicyclo[2.2.2]octanes
Electrophilic fluorination
Selectfluor

Field of Science*

1.4 Chemical sciences
3.1 Basic medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

Access to Document

10.1016/j.tet.2018.04.075

Cite this

@article{f5cb52494a29416a993c2bbac6aa8115,

title = "Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines",

abstract = "Electrophilic fluorination of Hantzsch-type 1,4-dihydropyridines with Selectfluor{\textregistered} led to the formation of new fluorinated 2,6-heptanediones - dialkyl 2,4-diacetyl-2,4-difluoro-3-phenylpentanedioates. Novel 2,6-heptanedione derivatives in reaction with hydrazine hydrate easily form 6-amino-4,7-difluoro-3-hydroxy-1,3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octanes instead of the corresponding diazepine derivatives. The obtained 2-оxa-6-azabicyclo[2,2,2]octanes are thermally stable at the temperatures below 50°С. At higher temperatures rearrangement of 2-oxa-6-azabicyclo[2,2,2]octanes offers new fluorine-containing pyrazolinone derivatives - alkyl esters of 2-fluoro-2-((4-fluoro-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)-3-oxobutanoates.",

keywords = "1,4-Dihydropyridines, 2,4-Diacetyl-2,4-difluoro-3-phenylpentanedioates, 2-Oxa-6-azabicyclo[2.2.2]octanes, Electrophilic fluorination, Selectfluor",

author = "Pikun, {Nadiia V.} and Kolesnyk, {Natalya P.} and Rusanov, {Eduard B.} and Aiva Plotniece and Martins Rucins and Arkadij Sobolev and Shermolovich, {Yuriy G.}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",

year = "2018",

month = jun,

day = "7",

doi = "10.1016/j.tet.2018.04.075",

language = "English",

volume = "74",

pages = "2884--2890",

journal = "Tetrahedron",

issn = "0040-4020",

publisher = "Elsevier Ltd.",

number = "23",

}

TY - JOUR

T1 - Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines

AU - Pikun, Nadiia V.

AU - Kolesnyk, Natalya P.

AU - Rusanov, Eduard B.

AU - Plotniece, Aiva

AU - Rucins, Martins

AU - Sobolev, Arkadij

AU - Shermolovich, Yuriy G.

PY - 2018/6/7

Y1 - 2018/6/7

N2 - Electrophilic fluorination of Hantzsch-type 1,4-dihydropyridines with Selectfluor® led to the formation of new fluorinated 2,6-heptanediones - dialkyl 2,4-diacetyl-2,4-difluoro-3-phenylpentanedioates. Novel 2,6-heptanedione derivatives in reaction with hydrazine hydrate easily form 6-amino-4,7-difluoro-3-hydroxy-1,3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octanes instead of the corresponding diazepine derivatives. The obtained 2-оxa-6-azabicyclo[2,2,2]octanes are thermally stable at the temperatures below 50°С. At higher temperatures rearrangement of 2-oxa-6-azabicyclo[2,2,2]octanes offers new fluorine-containing pyrazolinone derivatives - alkyl esters of 2-fluoro-2-((4-fluoro-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)-3-oxobutanoates.

AB - Electrophilic fluorination of Hantzsch-type 1,4-dihydropyridines with Selectfluor® led to the formation of new fluorinated 2,6-heptanediones - dialkyl 2,4-diacetyl-2,4-difluoro-3-phenylpentanedioates. Novel 2,6-heptanedione derivatives in reaction with hydrazine hydrate easily form 6-amino-4,7-difluoro-3-hydroxy-1,3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octanes instead of the corresponding diazepine derivatives. The obtained 2-оxa-6-azabicyclo[2,2,2]octanes are thermally stable at the temperatures below 50°С. At higher temperatures rearrangement of 2-oxa-6-azabicyclo[2,2,2]octanes offers new fluorine-containing pyrazolinone derivatives - alkyl esters of 2-fluoro-2-((4-fluoro-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)-3-oxobutanoates.

KW - 1,4-Dihydropyridines

KW - 2,4-Diacetyl-2,4-difluoro-3-phenylpentanedioates

KW - 2-Oxa-6-azabicyclo[2.2.2]octanes

KW - Electrophilic fluorination

KW - Selectfluor

UR - http://www.scopus.com/inward/record.url?scp=85046170403&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2018.04.075

DO - 10.1016/j.tet.2018.04.075

M3 - Article

AN - SCOPUS:85046170403

SN - 0040-4020

VL - 74

SP - 2884

EP - 2890

JO - Tetrahedron

JF - Tetrahedron

IS - 23

ER -

Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines

Abstract

Keywords*

Field of Science*

Publication Type*

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