Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

Background: Atropisomers are very interesting stereoisomers having axial chirality resulting from restricted rotation around single bonds and are found in various classes of compounds. ortho-Substituted arylpyridines are an important group of them. A regio- and atropselective Suzuki–Miyaura cross-co...

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Main Authors: Piotr Pomarański, Piotr Roszkowski, Jan K. Maurin, Armand Budzianowski, Zbigniew Czarnocki
Format: Article
Language:English
Published: Beilstein-Institut 2018-09-01
Series:Beilstein Journal of Organic Chemistry
Subjects:
Online Access:https://doi.org/10.3762/bjoc.14.214
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spelling doaj-402e6e0decdd4c05aeade61bac57d3d32021-02-02T00:16:41ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972018-09-011412384239310.3762/bjoc.14.2141860-5397-14-214Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridinePiotr Pomarański0Piotr Roszkowski1Jan K. Maurin2Armand Budzianowski3Zbigniew Czarnocki4Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, PolandFaculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, PolandNational Medicines Institute, Chełmska 30/34, 00-725 Warsaw, PolandNational Centre for Nuclear Research, 05-400 Otwock-Świerk, PolandFaculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, PolandBackground: Atropisomers are very interesting stereoisomers having axial chirality resulting from restricted rotation around single bonds and are found in various classes of compounds. ortho-Substituted arylpyridines are an important group of them. A regio- and atropselective Suzuki–Miyaura cross-coupling reaction on 3,4,5-tribromo-2,6-dimethylpyridine was studied.Results: Reactions with various amounts of ortho-substituted phenylboronic acids with 3,4,5-tribromo-2,6-dimethylpyridine gave a series of mono- di- and triarylpyridine derivatives which allowed to draw conclusions about the order of substitution. Also, the observed selectivity in the case of ortho-methoxyphenylboronic acid suggested an additional metal O-chelation effect in the transition state, apparently not present in the ortho-chloro analogues. The rotational barrier in selected atropisomers was determined on the basis of HT NMR and thermal epimerisation experiments. The structure of most presented atropisomeric derivatives of 2,6-dimethylpyridine was confirmed by single-crystal X-ray analysis. Racemic chiral, differently substituted atropisomers were also examined by 1H NMR spectroscopy in the presence of a chiral solvating agent.Conclusion: This regio- and atropselectivity may be generally applicable to other arylpyridine systems. A regio- and atropselective Suzuki–Miyaura cross-coupling process has been observed, giving an efficient access to a class of atropisomeric compounds. An opposite selectivity using a differently ortho-substituted phenylbornic acid was observed.https://doi.org/10.3762/bjoc.14.214arylpyridinesatropisomerismcross-couplingpalladiumSuzuki–Miyaura reaction
collection DOAJ
language English
format Article
sources DOAJ
author Piotr Pomarański
Piotr Roszkowski
Jan K. Maurin
Armand Budzianowski
Zbigniew Czarnocki
spellingShingle Piotr Pomarański
Piotr Roszkowski
Jan K. Maurin
Armand Budzianowski
Zbigniew Czarnocki
Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine
Beilstein Journal of Organic Chemistry
arylpyridines
atropisomerism
cross-coupling
palladium
Suzuki–Miyaura reaction
author_facet Piotr Pomarański
Piotr Roszkowski
Jan K. Maurin
Armand Budzianowski
Zbigniew Czarnocki
author_sort Piotr Pomarański
title Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine
title_short Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine
title_full Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine
title_fullStr Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine
title_full_unstemmed Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine
title_sort some mechanistic aspects regarding the suzuki–miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine
publisher Beilstein-Institut
series Beilstein Journal of Organic Chemistry
issn 1860-5397
publishDate 2018-09-01
description Background: Atropisomers are very interesting stereoisomers having axial chirality resulting from restricted rotation around single bonds and are found in various classes of compounds. ortho-Substituted arylpyridines are an important group of them. A regio- and atropselective Suzuki–Miyaura cross-coupling reaction on 3,4,5-tribromo-2,6-dimethylpyridine was studied.Results: Reactions with various amounts of ortho-substituted phenylboronic acids with 3,4,5-tribromo-2,6-dimethylpyridine gave a series of mono- di- and triarylpyridine derivatives which allowed to draw conclusions about the order of substitution. Also, the observed selectivity in the case of ortho-methoxyphenylboronic acid suggested an additional metal O-chelation effect in the transition state, apparently not present in the ortho-chloro analogues. The rotational barrier in selected atropisomers was determined on the basis of HT NMR and thermal epimerisation experiments. The structure of most presented atropisomeric derivatives of 2,6-dimethylpyridine was confirmed by single-crystal X-ray analysis. Racemic chiral, differently substituted atropisomers were also examined by 1H NMR spectroscopy in the presence of a chiral solvating agent.Conclusion: This regio- and atropselectivity may be generally applicable to other arylpyridine systems. A regio- and atropselective Suzuki–Miyaura cross-coupling process has been observed, giving an efficient access to a class of atropisomeric compounds. An opposite selectivity using a differently ortho-substituted phenylbornic acid was observed.
topic arylpyridines
atropisomerism
cross-coupling
palladium
Suzuki–Miyaura reaction
url https://doi.org/10.3762/bjoc.14.214
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