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Anthony J. Burke and Carolina Silva Marques

Catalytic Arylation Methods

From the Academic Lab to Industrial Processes

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Anthony J. Burke dedicates this book to his late father Dominic, for instilling a curiosity about the world we live in, and his mother Phyllis, for her constant support.

Carolina S. Marques would like to dedicate this book to her parents Lita and Zeca and her sister Gaby.

Preface

Many years ago, one of the authors (AJB) had the pleasure of conducting his first arylation reaction – which was a Heck–Mizoroki reaction between an activated pyrimidine and methyl acrylate – and he was struck by the simplicity and efficacy of the coupling process. Thus, a keen interest in these reactions was awakened, and this has been manifested in the recent research activities conducted in this group.

The book's main aim is an attempt to consolidate the body of key research over the last 10 years (and up to around 2014) on various catalytic methods which involve an arylation process; in most cases, transition metals are used, but there are some rare examples of the use of organocatalysts – a situation that we predict will definitely change in the near future due to the significant advances that have been made in this extremely competitive field of catalysis.

It should also be noted that in general all the chapters, except for one, are concerned with arylation processes that involve catalyzed aryl group transfer; the one chapter outside of this “genre” (Chapter 9) deals with the very important strategy of construction of the aryl unit via cycloaddition reaction approaches.

Our philosophy is a practical or a “hands-on” approach, as we put a strong emphasis on the applications of these methodologies for the synthesis of interesting compounds, such as active pharmaceutical ingredients (APIs) and agrichemicals as well as the components of functional materials. We also provide some simple selected experiments that the reader might have an interest in carrying out, particularly those from academic or educational environments. We have shown the importance of such molecules in the drug discovery, chemical biology, and electronics fields.

The book is organized into nine distinct chapters, each terminating with a short conclusion. Our bibliography is very extensive; however, the reader will note that overall there is a very strong reliance on recent literature (from the last 4–5 years), as so many major developments have taken place during this period, particularly in the field of C–H functionalization. One other reason is that many important reviews have been published in recent times on specific catalytic processes that involve arylation, and to avoid unnecessary repetition, we avoided repeating this material.

In Chapter 1, the authors present a general overview of the classical cross-coupling methods, such as Heck–Mizoroki, Suzuki–Miyaura, Sonogashira, Kumada, Negishi, Ullmann coupling, and modern methods for biaryl unit synthesis, with metals such as Fe and Co. This is a very extensive chapter.

In Chapter 2, which in many ways is an extension of Chapter 1 and much connected to Chapter 4, the authors present a general overview of the most common X–H (X = N, O, S) arylation methods, which have suffered an explosion of developments over the last 10 years or so. Methods, such as Buchwald–Hartwig and Chan–Lam–Evans coupling, are at the forefront of this chapter. This is a very extensive chapter.

In Chapter 3, the authors present a general overview on decarboxylative coupling reactions catalyzed by transition-metal catalysts. This is actually a very short chapter.

In Chapter 4, again, in many ways an extension of Chapters 1 and 2, the authors present a general overview of the most common C–H activation (or functionalization) arylation methods, which have suffered an explosion in activity and interest in the last 10 years or so. This is a very extensive chapter. There is a considerable overlap between some aspects of this chapter and those of Chapters 1 and 2.

In Chapter 5, the authors present a review of the state of the art of conjugated aryl 1,4-additions using transition-metal catalyzed systems. There is a strong emphasis on catalytic asymmetric additions with efficient chiral catalysts in response to the amenability of this method for obtaining enantiomerically pure compounds.

In Chapter 6, which is somewhat interconnected with Chapter 5, the catalytic arylation reactions at C=N bonds are discussed. Our group has made some key contributions to this area.

In Chapter 7, we focus on the arylation of carbonyl groups. Both enantioselective and nonasymmetric methods are discussed. The most important advances that have taken place in the last decade are presented.

In Chapter 8, which is complementary to the previous chapter, the direct arylation at the α-position of carbonyl compound substrates (e.g., amides and esters) is discussed. Once again, the catalytic systems and experimental conditions are carefully overviewed.

Chapter 9 is, in fact, different from all the other chapters, in that it involves the synthesis of aromatic rings from simpler precursors, instead of involving aryl transfer sequences. It homes in on basically one powerful strategy, the cycloaddition method, and here, the [2+2+2]-cyclotrimerization and the [3+2]-Huisgen cycloaddition and its more efficient modern variant, the “click-chemistry” copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions and the Bergman cyclization as well as the analogous Myers–Saito cyclization are discussed. The chapter is rich in many interesting examples, and focuses particularly on biomedical applications of azide–alkyne click-chemistry. This chapter will be of interest to readers in the biochemical and biological chemistry areas, as part of this material touches on these areas.

This project has been a very rewarding and enlightening experience to us, and I think, as a result, we have become a more knowledgeable pair of chemists, particularly in the field of catalytic arylation processes (a huge one, and rapidly getting bigger…).

Inevitably, with an ambitious project such as this, various errors will have “sneaked in” and “ambushed” our work: we apologize for this and hope our readers will understand. We also are aware that some literature material has not appeared, and again we apologize and hope our readers will understand that under the circumstances, it is impossible to include everything (particularly for such a massive field as catalytic arylations). What we selected was in fact material that we thought to be the most interesting to include.

The authors would like to thank the support and encouragement from their friends and family and from the Burke research group and other colleagues. AJB would particularly like to express his gratitude to his wife (Olivia) and kids (Simon and Daniel) for their tolerance and forbearance during the writing of this work.

The authors would also like to thank our editor Dr. Anne Brennführer and her team, Lesley Fenske and Claudia Nussbeck, at Wiley-VCH for their enormous patience with us, and for keeping us focused and within “reasonable distance” from the initial deadline set at the beginning. We would also like to acknowledge the mercurial and professional work conducted by our copy-editor, Esakki Rahini, and her team at SPi Global.

Anthony J. Burke

Carolina S. Marques

Evora, Portugal

October 2014

It should be noted that the topic of phase-transfer catalyst has not been included in this book.

List of Abbreviations

Ac acetyl
ABPP activity-based protein profiling
acac acetylacetonate
AChE acetylcholine esterase
Ad adamantyl
Ar aryl
BCN bicyclo[6.1.0]non-4-yne
BINAP 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl
BINOL [1,1′-binaphthalene]-2,2′-diol
BQ benzoquinone
BOM benzyloxymethyl
Bn benzyl
bpy 2,2′-bypiridine
Bu buthyl
Cat catalyst
CATPHOS 12,12′-bis(diphenylphosphino)-9,9′,10,10′-tetrahydro-11,11′-bi-9,10-ethenoanthracene
Cbz benzyloxycarbonyl
CDC cross-dehydrogenative coupling
CHD 1,4-cyclohexadiene
CMD concerted metallation deprotonation
COD cyclooctadiene
coe cyclooctene
Cp cyclopentadienyl
CPME cyclopentyl methyl ether
CSA camphorsulfonic acid
CTAB cetyltrimethylammonium
CuAAC copper(I)-catalyzed azide-alkyne cycloaddition
CuTC copper(I) thiophen-2-carboxylate
Cy cyclohexyl
DABCO 1,4-diazabicyclo[2.2.2]octane
dba trans, trans-dibenzylideneacetone
DCE dichloroethane
dcype 1,2-bis-(dicyclohexylphosphino) ethane
DFT density functional theory
DIOP (2,3-o-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane
Dipimp 2-(2,6-diisopropylphenyl)iminomethylpyridine
DMA dimethylacetamide
DME 1,2-dimethoxyethane
DMF N,N-dimethylformamide
dmphen 2,9-dimethyl-1,10-phenanthroline
DMSO dimethyl sulfoxide
dppb 1,4-bis(diphenylphosphino)butane
dppe diphenylphosphinethane
dppf 1,1′-bis(diphenylphosphino)ferrocene
DPPP 1,3-bis(diphenylphosphino)propane
DSC dye sensitized solar cells
DTBP 2,6-di-tert-butylpyridine
dtbpf di-tert-butylphosphino ferrocene
EA elementar analysis
ee enantiomeric excess
EI electron ionization
Et ethyl
er enantiomeric ratio
ESI electrospray ionization
EWG electron withdrawing group
Fc ferrocenyl
GC gas chromatography
GLC gas-liquid chromatography
GPC gel-permeation-chromatography
HCV hepatitis C virus
HheC halohydrin dehalogenase
HMDS hexamethyldisilazane
HMPA hexamethylphosphoramide
HPLC high performance liquid chromatography
HQ hydroquinone
HRMS high resolution mass spectrometry
IL ionic liquid
IMS industrial methylated spirits (approximate composition is EtOH 94%, MeOH 5%, and water 1%)
IPA iso-propyl alcohol
IR infra-red
IPr 1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene
KIE kinetic isotope effect
LDA lithium diisopropylamide
LHMDS lithium hexamethyldisilizane
Me methyl
Mes mesityl group
MNP magnetic nanoparticles
MOP (+)-2-(diphenylphosphino)-2′-methoxy-1,1′-binaphthyl
MPEG monomethylated poly(ethylene glycol)
MS molecular sieves
Ms mesyl
MTBE methyl tert-butyl ether
NLO non-linear optical properties
NHC N-heterocyclic carbene
NMM N-methyl morpholine
NMP N-methylpyrrolidinone
NMR nuclear magnetic resonance
Nuc nucleophile
OTf triflate
PDI polydispersity index
PG protecting group
Ph phenyl
Pht phthalimidoyl
Pin pinacol
PMP 4-methoxyphenyl
iPr iso-propyl
PTFE poly(tetrafluoroethene)
RAFT reversible addition-fragmentation chain transfer
Rx reaction
SEM scanning electron microscopy [2-(Trimethylsilyl)ethoxy]methylacetal
SIPr 1,3-bis-(2,6-diisopropylphenyl)-4,5-dihydroximidazol-2-ylidene
SiaNAz N-azidoacetyl sialic acid
SPAAC strain-promoted azide-alkyne cycloaddition
SPhos 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl
TASF tris(diethylamino)sulfonium difluoro(trimethyl)silicate
TBAA tetrabutylammonium acetate
TBAB tetra-n-butylammonium bromide
TBAC tetrabutylammonium chloride
TBAF tetrabutylammonium fluoride
TBS tert-butyldimethylsilyl
TBTA tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine
TEMPO 2,2,6,6-tetramethyl-1-piperidinyloxy
Tf trifluoromethanesulfonyl (trifyl)
TFA trifluoroacetic acid
TGS target guided synthesis
THF tetrahydrofuran
THPTA tris(3-hydroxypropyltriazolylmethyl)amine
TIPS triisopropylsilyl group
TLC thin-layer-chromatography
TMP 2,2,6,6-tetramethylpiperidyl
TMEDA N,N,N′,N′-tetramethylethane-1,2-diamine
TMS tetramethylsilane
TOF time-of-flight
TON turn over number
Tol tolyl
TPPTS 3,3′,3″-phosphanetriyltris(benzenesulfonic acid) trisodium salt (sodium triphenylphosphine trisulfonate)
TPP triphenylphosphane
tr retention time (for HPLC or GC)
Ts 4-toluenesulfonyl
XPhos 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl