Strategies for Palladium-Catalyzed Non-directed and Directed C bond H Bond Functionalization

Strategies for Palladium-Catalyzed Non-directed and Directed C-H Bond Functionalization portrays the complete scope of these two aspects of C-H bond functionalization in a single volume for the first time. Featured topics include the influence of palladacyclic systems in C-H bond functionalization (need for newer catalytic systems for better efficiency), mechanistic aspect of the functionalization strategies leading to better systems, and applications of these methodologies to natural product synthesis and material synthesis.

• Addresses the involvement of catalytic systems (palladacycles) for better functionalization of (hetero)arenes to emphasize the need for developing better, more selective systems
• Covers the use of powerful mechanistic tools for understanding and assisting the development of better functionalization strategies
• Discusses the finer aspects of C-H bond functionalization, such as control of regioselectivity with or without directing groups
• Includes a chapter detailing the synthesis of naturally occurring molecules or functional molecules via both pathways for assessing the applicability of the functionalization strategies

• Language: English
• Publisher: Elsevier Science
• Release date: May 23, 2017
• ISBN: 9780128052556

Book preview

Strategies for Palladium-Catalyzed Non-Directed and Directed C H Bond Functionalization

Edited by

Anant R. Kapdi

Institute of Chemical Technology, Mumbai, India

Debabrata Maiti

Indian Institute of Technology, Mumbai, India

Latest Trends in Palladium Chemistry

Series Editors

Anant R. Kapdi

Debabrata Maiti

Table of Contents

Cover image

Title page

Copyright

List of Contributors

Foreword

Chapter 1. Introduction

Abstract

Chapter 2. Directed CH Bond Functionalization Strategies for Synthesis

Abstract

2.1 Introduction

2.2 Ortho-Palladated CH Bond Functionalization via Directing Group Effect

2.3 Conclusion

References

Chapter 3. Nondirected CH Bond Functionalizations of (Hetero)arenes

Abstract

3.1 Introduction

3.2 Reactions With Halides

3.3 Reactions With Pseudohalides

3.4 Conclusion

References

Chapter 4. Palladium-Catalyzed Directed Arylation of Unactivated C(sp³)H Bonds

Abstract

4.1 Introduction

4.2 Palladium-Catalyzed C(sp³)H Arylation Directed by Monodentate DGs

4.3 Palladium-Catalyzed C(sp³)H Arylation Directed by Bidentate DGs

4.4 Palladium-Catalyzed C(sp³)H Arylation Using Transient DGs

4.5 Palladium-Catalyzed Asymmetric C(sp³)H Arylation

4.6 Conclusions and Outlook

References

Chapter 5. CH Bond Functionalization at the Benzene Core of Indoles and Indolines (Excluding C-2 and C-3)

Abstract

5.1 Palladium-Catalyzed CH Bond Functionalization of Indole

5.2 Palladium-Catalyzed CH Bond Functionalization of Indolines

5.3 Conclusions

List of Abbreviations

References

Chapter 6. Palladium-Catalyzed Carbonylative and Carboxylative CH Functionalization Reactions: Importance and Role of Regioselectivity

Abstract

6.1 Introduction

6.2 Carbonylative CH Functionalization of Arenes in the Presence of Directing Group

6.3 Carbonylative C(sp²)H Functionalization of Heteroarenes

6.4 Carboxylative CH Bond Functionalization

6.5 Conclusion and Future Outlook

References

Chapter 7. Flow Chemistry Perspective for CH Bond Functionalization

Abstract

7.1 Introduction

7.2 Advantages of Using Continuous-Flow Microreactor Technology for CH Activation

7.3 Cross-Dehydrogenative Coupling in Continuous Flow

7.4 Rh-Catalyzed CH Activation Reactions in Continuous Flow

7.5 Palladium-Catalyzed C(sp³)H Activation Reactions in Continuous Flow

7.6 Ru-Catalyzed CH Activation Reactions in Continuous Flow

7.7 Intramolecular CH Activation Reactions in Continuous Flow

7.8 Ortho-Directed Hydrogen/Deuterium Isotope Exchange via Iridium-Catalyzed CH Activation

7.9 Conclusion

References

Chapter 8. Directed Meta-Selective CH Bond Functionalizations

Abstract

8.1 Introduction

8.2 Directing Group Assisted Meta-CH Functionalization

8.3 Ortho-Directing Group-Assisted and Norbornene-Mediated Meta-CH Functionalization

8.4 Formal Meta-CH Functionalization Using a Traceless Directing Group

8.5 Conclusion

Abbreviations

References

Chapter 9. Recent Advances in Distal Aliphatic sp³ CH Functionalization

Abstract

9.1 Introduction

9.2 Scope of Functionalization

9.4 Conclusion

References

Chapter 10. Palladacycles for Directed and Nondirected CH Bond Functionalization of (Hetero)arenes

Abstract

10.1 Introduction

10.2 Palladacycle PreCatalyst in CH Functionalization

10.3 Palladacycle Intermediate in CH Functionalization

10.4 Conclusion

Abbreviations

References

Chapter 11. Mechanistic/Organometallic Aspects of Palladium-Catalyzed CH Bond Functionalization

Abstract

11.1 Introduction

11.2 Early Findings

11.3 Palladium-Catalyzed CH Activation Pathways

11.4 Conclusion

Acknowledgments

List of Abbreviations

References

Chapter 12. Recent Developments in Palladium-Catalyzed Natural Product Synthesis via CH Activation

Abstract

12.1 Introduction

12.2 Total Synthesis of Aspidospermidine

12.3 Total Synthesis of (+) -Lithospermic Acid

12.4 Total Synthesis of Pipercyclobutanamide A

12.5 Total Synthesis of Piperarborenine B and D

12.6 Total Synthesis of Podophyllatoxin

12.7 Total Synthesis of Clavicipitic Acid

12.8 Total Synthesis of Hibispeptin A

12.9 Divergent Synthesis of Aeruginosins (sp³ CH Alkenylation and Arylation)

12.10 Total Synthesis of (+) Linoxepin

12.11 Rapid Total Synthesis of Rhazinal

12.12 Total Synthesis of Gamendazole

12.13 Total Synthesis of (+/−) Rhazinilam

12.14 Conclusion

References

Index

Copyright

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List of Contributors

Bhalchandra M. Bhanage,     Institute of Chemical Technology, Mumbai, Maharashtra, India

Aniruddha Dey,     Indian Institute of Technology Bombay, Mumbai, Maharashtra, India

Uttam Dhawa,     Indian Institute of Technology Bombay, Mumbai, Maharashtra, India

Ian J.S. Fairlamb,     University of York, York, United Kingdom

Prashant Gautam,     Institute of Chemical Technology, Mumbai, Maharashtra, India

Vijay Gayakhe,     Institute of Chemical Technology, Mumbai, Maharashtra, India

Aniket Gholap,     Institute of Chemical Technology, Mumbai, Maharashtra, India

Ye-Qiang Han,     Zhejiang University, Hangzhou, China

Fang Hu,     Zhejiang University, Hangzhou, China

Lin-Yu Jiao,     Northwest University, Xi’an, Shaanxi, PR China

Anant R. Kapdi,     Institute of Chemical Technology, Mumbai, Maharashtra, India

Fuk-Yee Kwong

The Hong Kong Polytechnic University, Kowloon, Hong Kong

The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

Gabriele Laudadio,     Eindhoven University of Technology, Eindhoven, The Netherlands

Gang Li,     Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, China

Bin Liu,     Zhejiang University, Hangzhou, China

Debabrata Maiti,     Indian Institute of Technology Bombay, Mumbai, Maharashtra, India

Timothy Noël,     Eindhoven University of Technology, Eindhoven, The Netherlands

Martin Oestreich,     Technical University of Berlin, Berlin, Germany

Benudhar Punji,     CSIR-National Chemical Laboratory (CSIR-NCL), Pune, Maharashtra, India

Bing-Feng Shi,     Zhejiang University, Hangzhou, China

Vineeta Soni,     CSIR-National Chemical Laboratory (CSIR-NCL), Pune, Maharashtra, India

Neetipalli Thrimurtulu,     Indian Institute of Technology Bombay, Mumbai, Maharashtra, India

Chandra M.R. Volla,     Indian Institute of Technology Bombay, Mumbai, Maharashtra, India

Shun-Man Wong,     The Hong Kong Polytechnic University, Kowloon, Hong Kong

Foreword

H bonds with close dissociation energies, achieving positional selectivity in intermolecular reactions continues to be the key challenge. While the early studies by Chatt and Fujiwara/Moritani (vide supraH activation, palladium catalysis displayed a yet unparalleled broad substrate scope.

H activation was illustrated by efficient syntheses of natural products, novel polymerization techniques, and the late-stage modification of bioactive compounds, such as nucleobases or peptides in a bioorthogonal fashion.

H activation chemistry will only be unleashed through the transition from academic research to industrial applications on scale.

Lutz Ackermann, Göttingen, August 2016

H functionalizations have revolutionized the efficiency of heterocycle syntheses, leading to an overall streamlining of the construction of increasingly complex target structures. Particularly, oxidative transformations were identified as versatile tools for the effective de novo synthesis of, among others, oxygen-, nitrogen-, and phosphorous-containing heterocycles.

H activation chemistry.

H metalations, largely with the aid of 4d transition metal catalysts based on palladium, rhodium, or ruthenium. Thereby, challenging heteroarene functionalizations proved ultimately viable under exceedingly mild reaction conditions.

H bonds.

Chapter 1

Introduction

Aniruddha Dey¹, Anant R. Kapdi² and Debabrata Maiti¹,    ¹Indian Institute of Technology Bombay, Mumbai, Maharashtra, India,    ²Institute of Chemical Technology, Mumbai, Maharashtra, India

Abstract

This is an introductory chapter discussing the variety of palladium-catalyzed C−H bond functionalization strategies in synthesis. A link to all the succeeding chapters has been made to allow readers to have a better idea about the flow of the book.

Keywords

Palladium-catalyzed; C−H bond functionalization; directed functionalization; nondirected functionalization; natural products; mechanisms

Organic chemistry has often been nominated as collateral to a celestial divinity bestowing Earth with the art of creation of life. Since the realization of a tangible cognizance about the prowess of this wonderful repository, mankind began their venture into developing deeper comprehension about the same. Theories akin to "VitalismH activation in recent years has further advanced the chain of development in regioselective functionalization. Additionally, curious quests to blend computational tools with synthetic methodology have unlocked a new field of inquiry and élan.

H functionalization-based strategies. Renowned research scholars have penned a collective treatise from their distinctive fields of interest, and pooled a coherent discussion about the fundamental concepts. Insightful and detailed address of the intricacies for the various methodologies further mark the cogent and analytical comprehension of the ideal mindsets of the 21st century chemists. However, the variety of metals used for catalytic conversions stands legion, and a vivid discourse encompassing all of them is beyond a corporeal attempt. Undoubtedly, the countable occasions in which palladium was used to perform such historical transformations are innumerable. This could be attributed to its greater catalytic efficiency, ease of procurement, and a multitude of advantages, coupled with the cost-effectiveness. Subsequent chapters in this book therefore revolve around chemical strategies which discern palladium as a catalyst, and thus rightfully recognize it as the protagonist in the book’s context (Fig. 1.1).

Figure 1.1 Schematic representation of the various aspects of palladium-catalyzed protocols covered in this book.

H activation-based transformation based on the effective and logical use of ligand control-based strategies.

H bond functionalization, Wong et al. discuss viable strategies undertaken for synthesis of biheteroarenes. The latter class of compounds enjoy a celebrated mention among a multitude of applicative fields like biological and pharmaceutical materials, and natural products, as well as in synthetic research. Correspondingly, a deep insight into the contemporary synthetic procedures which allow their production is significant. Wong et al. underline nondirected catalytic routes used in the last decade for effectuating the synthesis of biheteroarenes from simple starting precursors. These ensure cost-effective and greener alternatives to the directing group-based functionalization phenomenon. The chapter talks about strategies for palladium-catalyzed cross-coupling reactions between arenes/heteroarenes and arylhalides. Owing to the harsh synthetic procedures required for preparation of non-commercially available arylhalides, application of pseudohalides for biheteroarene synthesis is discussed as well.

H centers have been discussed by Dey et al. in a later chapter of this book.

C bond formation reactions are detailed in this chapter.

H carbonylation has been emphasized. Further, the same stretches over a discussion on carbonylation reactions with heterocyclic systems containing single or multiple heteroatoms. Carboxylative reactions which typify the use of CO2 as a reacting agent are also mentioned towards the close of the chapter.

H activation reactions that proceed with shorter time scales and precise selectivity. Integrated multistep synthesis coupled with effective scalability augment the attractiveness of this approach in a practical laboratory setup.

H functionalization chemistry: metaH functionalization at the distal meta- position of an arene. Pioneered by Yu in 2012, directed metaO bonds continues to make way at the metaH bond activation in an arene core. Gang Li pens a chronological sequence of the gradual evolution of meta-functionalization. The latter popularizes an emerging class of cleavable directors which were subsequently brought to operational existence by the Yu, Tan, Maiti, and Li groups to perform distinguished metaH olefination, acetoxylation, arylation, hydroxylation, and iodination.

H bonds catalyzed by palladium precatalysts. As discussed in H functionalization which have been made possible through the employment of an assortment of strategies.

In H bond functionalizations that are proposed with experimental evidence. Some of the described palladacycle intermediates are shown to be competent as catalyst precursors, coupled with their stability during the functionalization phenomenon.

H bond functionalization as part of its context. Gayakhe et al. present an account of the fundamental and key concepts behind the operation of organometallic catalysis. With the earlier reports about oxidative addition to H2, the authors discuss the basic mechanistic pathways involving electrophilic aromatic substitution and oxidative additions. Further, owing to the recent reports on the popularity of cyclometallation−demetallation (CMD)-based reaction schemes, an insight into the CMD mechanism is provided. Finally, the discussion concludes with mention of the Heck-type carbometallation pathways that lessen the requirement for any preactivation step. The latter is particularly popular in the case of palladium-catalyzed cross-coupling reactions.

H functionalization has been showcased as an effective method of ensuring functional group installation in a highly site-selective manner. Examples from recent literature reports are detailed with substantial analysis of the reaction pathways. This chapter is therefore important from the point of view of developing a sound concept about simplifying retrosynthetic disconnections in the course of synthesizing any complex molecules as the target motif.

H functionalization in recent times, aims to inculcate cognizance among the scientific fraternity about the same, and wishes to encourage chemists of both the present and future generations to contribute their ideas towards the welfare of the scientific community, as well as for all and sundry.

Chapter 2

Directed C H Bond Functionalization Strategies for Synthesis

Ian J.S. Fairlamb¹ and Anant R. Kapdi²,    ¹University of York, York, United Kingdom,    ²Institute of Chemical Technology, Mumbai, Maharashtra, India

Abstract

Palladium-catalyzed directed arylations have provided researchers with a useful handle to synthesize molecules of relevance without the requirement for modification of substrates. Different functional groups present on the molecules could commonly act as strongly or weakly coordinating ligands allowing the facile conversion of the substrates to the desired molecules. Major advances have taken place in this area in the past few years, which is the main focus of discussion in this chapter.

Keywords

Palladium-catalyzed; directed arylations; ortho-palladated; C–H activation; coordinating ligands

Contents

2.1 Introduction 9

H Bond Functionalization via Directing Group Effect 11

2.2.1 Effect of Coordination Capacity on Functionalization 11

2.3 Conclusion 45

References 46

2.1 Introduction

C bonds could be achieved via these processes, cost escalation for the multi-step reactions renders the overall process commercially less attractive. Circumventing this problem would involve the possibility of employing an unfunctionalized substrate that could be directly functionalized without the requirement for a prefunctionalization step.

H bonds could provide researchers with the required sustainable solution that could also be cost-effective.H bonds have now been replaced in recent years with efficient catalytic activation processes employing transition metals such as Ru, Cu, Fe, Ni, Rh, and Pd.³ Palladium, with its unique reactivity, has been at the forefront in these processes, allowing the functionalizations to be performed under milder conditions.

H bonds allowing selective functionalization (carbon, etc.

Figure 2.1 H bond activation.

H functionalization, is also undertaken. Most of the examples discussed herein are related to ortho-functionalization of aromatic substrates proceeding commonly via a cyclopalladated intermediate that governs the selectivity in these reactions. Functionalization of other sites on the benzene ring or on aliphatic substrates falls outside the scope of this chapter, and readers are advised to refer to some of the recent literature on this topic,⁴ as well as the further chapters of this book where these topics are discussed in depth by Li and Maiti.

2.2 Ortho-Palladated C H Bond Functionalization via Directing Group Effect

H bond functionalization are listed below:

(a) Strongly coordinating ligands: pyridine, anilide, urea, etc.

(b) Weakly coordinating ligands: ketone, hydroxyl, amides, phosphate, esters, sulfonamides, carbamates, formate esters, alkynes, alkenes, carboxylic acids, etc.

H bond functionalization reactions; however, based on the number of examples in literature, only the most applicable ligand systems (listed above) will be discussed in detail in this chapter.

2.2.1 Effect of Coordination Capacity on Functionalization

At the outset it is important to understand the effect of the coordinating power of ligand on the effectiveness of selective