Metal Free C-H Functionalization of Aromatics: Nucleophilic Displacement of Hydrogen

289 Pages·2014·33.61 MB·English

by  Valery Charushin

Topics in Heterocyclic Chemistry 37
Series Editors: B.U.W. Maes · J. Cossy · S. Polanc
Valery Charushin
Oleg Chupakhin Editors
Metal Free C–H
Functionalization
of Aromatics
Nucleophilic Displacement of Hydrogen
37
Topics in Heterocyclic Chemistry
SeriesEditors:
B.U.W. Maes, Antwerpen, Belgium
Janine Cossy, Paris, France
Slovenko Polanc, Ljubljana, Slovenia
Editorial Board:
D. Enders, Aachen, Germany
S.V. Ley, Cambridge, UK
G. Mehta, Bangalore, India
K.C. Nicolaou, La Jolla, CA, USA
R. Noyori, Hirosawa, Japan
L.E. Overmann, Irvine, CA, USA
A. Padwa, Atlanta, GA, USA
Aims and Scope
The series Topics in Heterocyclic Chemistry presents critical reviews on present
andfuturetrendsintheresearchofheterocycliccompounds.Overallthescopeisto
covertopicsdealingwithallareaswithinheterocyclicchemistry,bothexperimental
andtheoretical,ofinteresttothegeneralheterocyclicchemistrycommunity.
The series consists of topic related volumes edited by renowned editors with
contributionsofexpertsinthefield.
More information about this series at
http://www.springer.com/series/7081
Valery Charushin • Oleg Chupakhin
Editors
Metal Free C–H
Functionalization of
Aromatics
Nucleophilic Displacement of Hydrogen
With contributions by
V.N. Charushin • O.N. Chupakhin • I. Gallardo •
G. Guirado • A.V. Gulevskaya • Y. Kondo • M. Ma˛kosza •
A.F. Pozharskii • S. Shevelev • A. Starosotnikov •
K. Wojciechowski
Editors
ValeryCharushin OlegChupakhin
PostovskyInstituteofOrganicSynthesis; PostovskyInstituteofOrganicSynthesis;
UralFederalUniversity UralFederalUniversity
Ekaterinburg Ekaterinburg
Russia Russia
ISSN1861-9282 ISSN1861-9290(electronic)
ISBN978-3-319-07018-6 ISBN978-3-319-07019-3(eBook)
DOI10.1007/978-3-319-07019-3
SpringerChamHeidelbergNewYorkDordrechtLondon
LibraryofCongressControlNumber:2014946582
#SpringerInternationalPublishingSwitzerland2014
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Preface
One ofthe current trends indevelopment ofboth academic andindustrialorganic
synthesis is orientation of chemists on using “chlorine-free” ecologically benign
processes, based on direct methods of C–H functionalization of aromatic
compounds,avoidinghalogenatedstartingmaterialsorintermediates.
Thesynthesisandstructuralmodificationsofaromaticsystemshavealwaysbeen
asubjectofconsiderableinteresttomanychemists.Electrophilicaromaticsubsti-
tution of hydrogen S Ar and nucleophilic aromatic substitution of halogen and
E
other good leaving anionic groups S Aripso, became the main synthetic
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methodologiesandbasicindustrialprocessesofthelastcentury.Formanydecades
theyhavebeenexploitedbychemiststoobtainenormousnumberofderivativesof
thisimportantclassoforganiccompounds.
A great variety of effective metal-catalyzed cross-coupling reactions (Heck,
Stille, Suzuki-Mijaura, Sonogashira, Kumada, Negishi, Buchwald-Hartwig,
Hijama, and others) have been advanced during the last three decades, however
mostofthesecatalyticmethodsarealsobasedonusingarylhalogenides,asstarting
materials.Thesituationisfarfromidealfromanatomeconomypointofview(for
instance, bromination of aromatics – debromination), to say nothing of its poor
correspondence to other principles of the green chemistry. Besides that, metal-
catalyzed cross-coupling reactions often require the presence of palladium-
containingcatalysts andphosphorus-containingligands,tracesofwhich couldnot
be admitted in pharmaceutical products. This is why the roundtable of leading
globalpharmaceuticalcompanies,arrangedbytheAmericanChemicalSocietyand
Green Chemistry Institute, put the C–H activation of aromatics (including cross-
coupling reactions, avoiding the preparation of haloaromatics) in the list of
promising“aspirational”reactions(fordetailsee:[1]).
Webelievethatitisahightimetodrawattentionofbothacademicandindustrial
chemists to a relatively new synthetic methodology, which is based on the direct
metal-freenucleophilicdisplacementofhydrogeninaromaticsystems(S H).
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This volume of Topics in Heterocyclic Chemistry is composed of six chapters
presented by an international set of authors, which responded to our proposal to
v
vi Preface
review the recently published data on the S H reactions, proceeding without
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organometallicintermediates.
The chapter “Metal-Free С–Н Functionalization of Aromatic Compounds
Through the Action of Nucleophilic Reagents” by Valery Charushin and Oleg
Chupakhin (Postovsky Institute of Organic Synthesis; Ural Federal University,
Ekaterinburg, Russia) presents a general concept of the S H reactions. It is sup-
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posed to demonstrate a common character of the S H reactions, as a fundamental
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property of aromatic and hetero-aromatic compounds, and to show the practical
valueofmetal-freeC–Hfunctionalizationofaromatics.
The chapter “Nucleophilic Substitution of Hydrogen in Arenes and
Heteroarenes” by Mieczysław Ma˛kosza and Krzysztof Wojciechowski (Institute
ofOrganicChemistry,ThePolishAcademyofSciences,Warsaw,Poland)provides
uswiththecomprehensivereviewonbothoxidativeandeliminativeversionsofthe
S H reactions, including the so-called vicarious nucleophilic substitution, which
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appearstobeaveryessentialpartoftheS Hmethodology.Indeed,thepresenceof
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a vicarious (auxiliary) group facilitates elimination of hydrogen with pair of
electronsfromtheintermediatesH-adducts.
The chapter “Direct Functionalization of C–H Fragments in Nitroarenes as a
Synthetic Pathway to Condensed N-Heterocycles”, authored by Svyatoslav
Shevelev and Alexey Starosotnikov (Zelinsky Institute of Organic Chemistry,
Moscow, Russia), deals with the direct functionalization of C–H fragments in
nitroarenes, followed by intramolecular cyclizations, as an effective synthetic
pathwaytocondensednitrogenheterocycles.
The chapter “C–H Functionalizations of Heteroaromatic N-Oxides”, prepared
by Yoshinori Kondo (Tohoku University, Sendai, Japan), gives an excellent
account of the recent advances in the field of nucleophilic C–H functionalization
of heteroaromatic N-oxides, by using metal-free S H processes, as attractive
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environmentallybenignmethodsoforganicsynthesis.
Thechapter“TheS H-AminationofAromaticCompounds”,authoredbyAnna
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Gulevskaya and Alexander Pozharsky (Rostov-on-Don University, Russia),
presentsacomprehensivereviewonthedirectS Haminationofelectron-deficient
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heteroaromaticcompounds.Recentadvancesinthisareaandmanynewaspectsof
the S H amination are discussed, including new types of reagents, metal-free
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catalysts, solvents and the hydride ion acceptors. The review shows that the S H
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amination is rather promising synthetic alternative to both classic and transition
metal-catalyzedamino-dehalogenationreactions.
Finally, the chapter “Electrochemical C–H Functionalization of Arenes ” by
IluminadaGallardoandGonzaloGuirado(UniversityofBarcelona,Spain)provide
us with an excellent review showing a practical importance of electrochemical
methods for the direct C–H functionalization of aromatic and heteroaromatic
compounds– avery promising area thathas been advancedsignificantly by these
authors.
It is worth noting that three chapters of this volume have been written by the
Russian chemists, and it seems to be a good opportunity to discuss the results
Preface vii
obtainedbytheseresearchgroupsandtoreflectproperlyaconsiderablebodyofthe
dataontheS HreactionspublishedintheRussianchemicaljournals.
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Webelievethatnumerousexamplesandmethodsforthedirectmetal-freeC–H
functionalizationofarenesandheteroarenes,presentedbyaninternationalteamof
chemistsinsixchaptersofthisvolume,arenotonlycomplementarytoeachother,
butalsocreatethewholepictureoftheS Hreactions,enablingonetoestimatetheir
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currentscope,syntheticpotentialandvalueas“chlorine-free”ecologicallybenign
processes.
In conclusion, we would like to express our sincere gratitude to all authors for
theirvaluablecontributions.AlsowearethankfultoprofessorBertMaes(Univer-
sity of Antwerp, Belgium), who encouraged us to prepare this volume, and
Elizabeth Hawkins and Tanja Jaeger from Springer DE for their help and fruitful
cooperation.
Finally,weareverymuchobligedtoourfamiliesfortheirpatienceandunder-
standingduringpreparationofthemanuscript.
Ekaterinburg,Russia ValeryCharushinandOlegChupakhin
9December2013
Reference
1.ConstableDJCetal(2007)GreenChem9:41.
.
Contents
Metal-FreeC–HFunctionalizationofAromaticCompounds
ThroughtheActionofNucleophilicReagents. . . . . . . . . . . . . . . . . . . . 1
ValeryN.CharushinandOlegN.Chupakhin
NucleophilicSubstitutionofHydrogeninArenesandHeteroarenes. . . 51
MieczysławMa˛koszaandKrzysztofWojciechowski
DirectFunctionalizationofC–HFragmentsinNitroarenes
asaSyntheticPathwaytoCondensedN-Heterocycles. . . . . . . . . . . . . . 107
SvyatoslavShevelevandAlexeyStarosotnikov
C–HFunctionalizationofHeteroaromaticN-Oxides. . . . . . . . . . . . . . . 155
YoshinoriKondo
TheSH-AminationofHeteroaromaticCompounds. . . . . . . . . . . . . . . . 179
N
AnnaV.GulevskayaandAlexanderF.Pozharskii
ElectrochemicalC–HFunctionalizationofArenesandHeteroarenes. . . 241
IluminadaGallardoandGonzaloGuirado
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
ix