Heterocycles from Transition Metal Catalysis (eBook)

Contents 8
Foreword 10
Abbreviations 12
INTRODUCTION TO CATALYSIS 14
1.1 GENERAL CONSIDERATIONS 14
1.2 THE ELEMENTARY STEPS OF CATALYTIC REACTIONS 16
1.3 CLASSIFICATION OF THE CATALYTIC PROCESSES ON THE BASIS OF THE ELECTRONIC CHARACTER OF THE REAGENTS 27
1.4 REFERENCES 28
OVERVIEW OF CARBON-CARBON AND CARBON- HETEROATOM BOND FORMING REACTIONS 31
2.1. CROSS-COUPLING REACTIONS 31
2.2. HECK REACTION 33
2.3. BUCHWALD-HARTWIG REACTION 34
2.4. REACTIONS PROCEEDING WITH CO INSERTION 36
2.5. COPPER CATALYZED PROCESSES 38
2.6. REFERENCES 39
THE SYNTHESIS OF FIVE MEMBERED RINGS 41
3.1 TRANSMETALATION ROUTE 41
3.2 INSERTION ROUTE 45
3.3 CARBON-HETEROATOM BOND FORMATION 55
3.4 OTHER PROCESSES 68
THE SYNTHESIS OF SIX MEMBERED RINGS 78
4.1 TRANSMETALATION ROUTE 78
4.2 INSERTION ROUTE 81
4.3 CARBON-HETEROATOM BOND FORMATION 85
4.4 OTHER PROCESSES 89
4.5 REFERENCES 95
THE SYNTHESIS OF OTHER RING SYSTEMS 97
5.1 TRANSMETALATION ROUTE 97
5.2 INSERTION ROUTE 98
5.3 CARBON-HETEROATOM BOND FORMATION 100
5.4 OTHER PROCESSES 103
5.5 REFERENCES 105
THE FUNCTIONALIZATION OF FIVE MEMBERED RINGS 107
6.1 TRANSMETALATION ROUTE 107
6.2 INSERTION ROUTE 127
6.3 CARBON-HETEROATOM BOND FORMATION 132
6.4 OTHER PROCESSES 138
6.5 REFERENCES 142
THE FUNCTIONALIZATION OF SIX MEMBERED RINGS 147
7.1 TRANSMETALATION ROUTE 147
7.2 INSERTION ROUTE 165
7.3 CARBON-HETEROATOM BOND FORMATION 174
7.4 OTHER PROCESSES 178
7.5 REFERENCES 181
THE FUNCTIONALIZATION OF OTHER RING SYSTEMS 185
8.1 TRANSMETALATION ROUTE 185
8.2 INSERTION ROUTE 198
8.3 CARBON-HETEROATOM BOND FORMATION 200
8.4 OTHER PROCESSES 201
8.5 REFERENCES 203
INDEX 205

Chapter 7
THE FUNCTIONALIZATION OF SIX MEMBERED RINGS (p. 137-138)

The transition metal catalyzed functionalization of six membered heterocycles constitutes a major chapter of this book. The abundance of examples might be tracked down to two reasons: i) the large number of available haloazines, ii) the marked reactivity of haloazines in catalytic reactions, which originates in their electron deficient nature. In general the reactivity of a 2-chloropyridine derivative is comparable to a bromoarene, while a bromopyridine behaves more like an iodobenzene derivative. The increasing number of nitrogen atoms in the ring makes chlopyridazines or chloropyrimidines reactive enough to participate in transition metal catalyzed processes. The potential biological activity of six membered heterocyclic systems and their abundance as structural motif in natural products drove synthetic chemists to exploit their transformations. This chapter is mainly dedicated to the reactions of monocyclic six membered heterocycles and their benzologues. The chemistry of other condensed systems of importance, such as purines and pyrons, is discussed in Chapter 8.

7.1 TRANSMETALATION ROUTE
Probably the most thoroughly studied transition metal catalyzed transformation of six membered systems is their participation in crosscoupling reactions. Due to the vastness of this field we present only some representative examples for the different reaction types. In this chapter reactions where a haloazine is used to introduce the six membered ring on the palladium in the oxidative addition and processes, where the azine moiety is transferred onto the catalyst in a transmetalation step will be discussed parallel. The featured reactions were divided into subclasses along the commonly used name reactions.

Suzuki coupling

The availability of reagents and their functional group tolerance led to the emergence of Suzuki coupling as the most utilized cross-coupling reaction of the recent years.1 Either haloazines are coupled with an organoboron reagent, or the azines are converted into boronate esters, boronic acids or boranes and react with aryl halides, the reaction usually proceeds equally well. The examples presented below will focus more on the latter case, the coupling of hetarylboron compounds.2 The coupling of pyrone derivatives is discussed in Chapter 8.1.

In equation 7.1. a 4-chloropyridine was coupled with diethyl(3- pyridyl)borane.3 The reaction was run in aqueous THF in the presence of potassium carbonate. The role of the base is to facilitate the transmetalation step through the formation of a borate ion, as organoboranes are usually not nucleophilic enough to transfer their organic moiety onto the palladium. An alternate function of the base is to increase the electrophilicity of the palladium through exchange of the halide to carbonate.