Atropisomerism in Asymmetric Organic Synthesis

Presents new methodologies, strategies, and unique catalysts emerged in the oxidative heterocoupling area and tackles some everlasting challenges.

Auteur

*Shinobu Takizawa, PhD, is Professor at SANKEN, Osaka University, Japan. His current research focuses on developing environmentally friendly organic synthetic processes. **Mohamed S. H. Salem, PhD, is Assistant Professor at SANKEN, Osaka University, Japan. His current research focuses on developing green synthetic approaches for the bottom-up synthesis of functionalized small organic molecules with various material-based applications.*

Texte du rabat

Unique overview of the recent synthetic methodologies of the atropisomeric molecules and their numerous practical applications Atropisomerism in Asymmetric Organic Synthesis: Challenges and Applications presents new methodologies, strategies, unique catalysts, and solutions to challenges in the area of oxidative heterocoupling. After a general introduction for the concept of atropisomerism, this book focuses on the recent advances in the atroposelective synthesis of axially chiral compounds and how these advances had a significant impact on several applications in asymmetric catalysis and the synthesis of natural products. The book covers the recent examples of metal-catalyzed (Cu, Fe, Ru, V, etc) and organocatalyzed atroposelective syntheses of axially chiral compounds using diverse approaches, including cross-coupling reactions, ring-opening reactions, formation of new aromatic rings, and desymmetrization via functional group transformation. The impact of these efficient strategies on various applications in asymmetric catalysis, total synthesis of natural products, synthesis of polycyclic heteroaromatics (PHAs), and the drug industry is also addressed. Edited by two highly qualified academics, Atropisomerism in Asymmetric Organic Synthesis explores sample topics including:

• Iron- and ruthenium-catalyzed atroposelective synthesis of axially chiral compounds and the catalytic applications of multinuclear zinc complexes with axially chirality
• Vanadium-catalyzed atroposelective coupling of arenols and application in the synthesis of polycyclic heteroaromatics PHAs
• Mechanisms of atroposelective Suzuki-Miyaura coupling towards axially chiral biaryls and organocatalytic enantioselective formation of atropisomers
• Synthesis of atropisomers via enantioselective ring-opening reactions and the impact of axially chiral ligands and catalysts derived from atropisomeric binaphthyl structures
• Binaphthyl-based chiral DMAP derivatives in enantioselective transformations and catalytic atroposelective oxidative coupling in natural product synthesis Enabling readers to comprehensively understand the development history, research status, and potential of atropisomeric synthesis, Atropisomerism in Asymmetric Organic Synthesis is an essential, up-to-date reference for researchers and scientists in the field.

Contenu
Preface

PART I ATROPOSELECTIVE SYNTHESIS

1 Introduction

1.1. Molecular chirality and atropisomerism
1.2. Atropisomerism in asymmetric organic synthesis
1.3. Atropisomerism: Challenges and applications

2 Iron- and Ruthenium-catalyzed Atroposelective Synthesis of Axially Chiral Compounds
2.1. Introduction
2.2. Oxidative homocoupling of 2-naphthols to BINOL and its derivatives
2.3. Oxidative cross-coupling of 2-naphthols to asymmetric BINOLs
2.4. Oxidative spirocyclization of 2-naphthols
2.5. Conclusion

3 Vanadium-catalyzed Atroposelective Coupling of Arenols and Application in the Synthesis of Polycyclic Heteroaromatics PHAs
3.1. Introduction
3.2. Chiral vanadium catalysis in homo-coupling of hydroxycarbazoles
3.3. Chiral vanadium catalysis in hetero-coupling of hydroxycarbazole with 2-naphthols
3.4. Enantioselective synthesis of oxa[9]helicenes via chiral vanadium complex-catalyzed homo-couplings of polycyclic phenols
3.5. Enantioselective synthesis of oxaza[7]dehydrohelicenes via chiral vanadium complex-catalyzed hetero-couplings of 3-hydroxycarbazoles and 2-naphthols
3.6. Summary and Conclusion

4 Atroposelective Suzuki?Miyaura coupling towards Axially Chiral Biaryls: Mechanistic Insight
4.1. Introduction
4.2. Mechanism insight of SMC reaction and enantiodetermining step
4.3. Asymmetric SMC reaction
4.4. Conclusion

5 Organocatalytic Enantioselective Formation of Atropisomers
5.1. Introduction
5.2. Aminocatalysis
5.3. Brønsted base catalysis
5.4. Phase Transfer Catalysis
5.5. Chiral Phosphoric Acids
5.6. Conclusions

6 Synthesis of Atropisomers via Enantioselective Ring-Opening Reactions
6.1. Introduction
6.2. Asymmetric ring-opening of biaryl lactones and its derivatives
6.3. Asymmetric ring-opening reactions via C-I bond cleavage
6.4. Asymmetric ring-opening reactions via C-N and C-P bonds cleavage
6.5. Asymmetric ring-opening reactions via C-C and C-Si bonds cleavage
6.6. Asymmetric ring-opening reactions via C-O and C-S bonds cleavage
6.7. Oriented asymmetric ring-opening via transient pentacyclic metal species
6.8. Summary and Conclusions

PART II CHALLENGES AND APPLICATIONS

7 Axially Chiral Ligands and Catalysts Derived from Atropisomeric Binaphthyl Structures
7.1. Introduction
7.2. Chiral ligands derived from BINOLs
7.3. Chiral ligands derived from BINAMs
7.4. Chiral ligands derived from NOBINs
7.5. Chiral organocatalysts derived from BINOLs
7.6. Chiral organocatalysts derived from BINAMs
7.7. Chiral organocatalysts derived from NOBINs
7.8. Chiral ligands and catalysts derived from other Binaphthyl motifs
7.9. Summary and Outlook

8 Multinuclear Zinc Catalysts with Axially Chirality
8.1. Pioneering works on BINOL-Zn System
8.2. Enantioselective addition reaction of dialkylzinc to aldehydes using BINOL additive
8.3. Catalytic asymmetric alkynylation of aldehydes
8.4. Catalytic asymmetric Diels-Alder reaction
8.5. Catalytic asymmetric epoxidation of enones
8.6. Catalytic asymmetric direct Aldol reaction
8.7. Catalytic asymmetric iodofunctionalization of alkenes
8.8. Conclusions

9 Binaphthyl-based Chiral DMAP Derivatives in Enantioselective Transformations
9.1. Introduction
9.2. Binaphthyl-based chiral DMAP derivatives
9.3. Intramolecular acyl transfer reactions
9.4. Intermolecular acyl transfer reactions
9.5. Summary and Conclusions

10 Catalytic Atroposelective Oxidative Coupling in Natural Product Synthesis
10.1. Introduction
10.2. Copper-catalyzed asymmetric oxidative coupling to construct a chiral axis
10.3. Vanadium-catalyzed asymmetric oxidative coupling to construct a chiral axis
10.4. Enzymatic strategies to synthesize natural products via atroposelective coupling
10.5. Conclusion

11 Atropisomerism in Drug Discovery and Development
11.1. Introduction
11.2. Configuration assignment of atropisomeric drugs
11.3. Classification of atropisomeric drugs according to the rotational energy barrier
11.4. Analysis of atropisomeric drugs across the pharmaceutical market drugs
11.5. Introducing atropisomerism to modulate selectivity
11.6. Challenges for atropisomerism within drug discovery
11.7. Conclusions