Science of Synthesis Knowledge Updates 2014 Vol. 1 E-Book

• Herausgeber: Thieme
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1224

Veröffentlichungsjahr: 2014

Beschreibung

Science of Synthesis is a reference work for preparative methods in synthetic chemistry. Its product-based classification system enables chemists to easily find solutions to their synthetic problems.

Key Features:

• Critical selection of reliable synthetic methods, saving the researcher the time required to find procedures in the primary literature.
• Expertise provided by leading chemists.
• Detailed experimental procedures.
• The information is highly organized in a logical format to allow easy access to the relevant information.

The Science of Synthesis Editorial Board, together with the volume editors and authors, is constantly reviewing the whole field of synthetic organic chemistry as presented in Science of Synthesis and evaluating significant developments in synthetic methodology. Four annual volumes updating content across all categories ensure that you always have access to state-of-the-art synthetic methodology.

Leseprobe

Science of Synthesis

Science of Synthesis is the authoritative and comprehensive reference work for the entire field of organic and organometallic synthesis.

Science of Synthesis presents the important synthetic methods for all classes of compounds and includes:

Methods critically evaluated by leading scientists

Background information and detailed experimental procedures

Schemes and tables which illustrate the reaction scope

Preface

As the pace and breadth of research intensifies, organic synthesis is playing an increasingly central role in the discovery process within all imaginable areas of science: from pharmaceuticals, agrochemicals, and materials science to areas of biology and physics, the most impactful investigations are becoming more and more molecular. As an enabling science, synthetic organic chemistry is uniquely poised to provide access to compounds with exciting and valuable new properties. Organic molecules of extreme complexity can, given expert knowledge, be prepared with exquisite efficiency and selectivity, allowing virtually any phenomenon to be probed at levels never before imagined. With ready access to materials of remarkable structural diversity, critical studies can be conducted that reveal the intimate workings of chemical, biological, or physical processes with stunning detail.

The sheer variety of chemical structural space required for these investigations and the design elements necessary to assemble molecular targets of increasing intricacy place extraordinary demands on the individual synthetic methods used. They must be robust and provide reliably high yields on both small and large scales, have broad applicability, and exhibit high selectivity. Increasingly, synthetic approaches to organic molecules must take into account environmental sustainability. Thus, atom economy and the overall environmental impact of the transformations are taking on increased importance.

The need to provide a dependable source of information on evaluated synthetic methods in organic chemistry embracing these characteristics was first acknowledged over 100 years ago, when the highly regarded reference source Houben–Weyl Methoden der Organischen Chemie was first introduced. Recognizing the necessity to provide a modernized, comprehensive, and critical assessment of synthetic organic chemistry, in 2000 Thieme launched Science of Synthesis, Houben–Weyl Methods of Molecular Transformations. This effort, assembled by almost 1000 leading experts from both industry and academia, provides a balanced and critical analysis of the entire literature from the early 1800s until the year of publication. The accompanying online version of Science of Synthesis provides text, structure, substructure, and reaction searching capabilities by a powerful, yet easy-to-use, intuitive interface.

From 2010 onward, Science of Synthesis is being updated quarterly with high-quality content via Science of Synthesis Knowledge Updates. The goal of the Science of Synthesis Knowledge Updates is to provide a continuous review of the field of synthetic organic chemistry, with an eye toward evaluating and analyzing significant new developments in synthetic methods. A list of stringent criteria for inclusion of each synthetic transformation ensures that only the best and most reliable synthetic methods are incorporated. These efforts guarantee that Science of Synthesis will continue to be the most up-to-date electronic database available for the documentation of validated synthetic methods.

Also from 2010, Science of Synthesis includes the Science of Synthesis Reference Library, comprising volumes covering special topics of organic chemistry in a modular fashion, with six main classifications: (1) Classical, (2) Advances, (3) Transformations, (4) Applications, (5) Structures, and (6) Techniques. Titles will include Stereoselective Synthesis, Water in Organic Synthesis, and Asymmetric Organocatalysis, among others. With expertevaluated content focusing on subjects of particular current interest, the Science of Synthesis Reference Library complements the Science of Synthesis Knowledge Updates, to make Science of Synthesis the complete information source for the modern synthetic chemist.

The overarching goal of the Science of Synthesis Editorial Board is to make the suite of Science of Synthesis resources the first and foremost focal point for critically evaluated information on chemical transformations for those individuals involved in the design and construction of organic molecules.

Throughout the years, the chemical community has benefited tremendously from the outstanding contribution of hundreds of highly dedicated expert authors who have devoted their energies and intellectual capital to these projects. We thank all of these individuals for the heroic efforts they have made throughout the entire publication process to make Science of Synthesis a reference work of the highest integrity and quality.

July 2010

The Editorial Board

E. M. Carreira (Zurich, Switzerland)

C. P. Decicco (Princeton, USA)

A. Fuerstner (Muelheim, Germany)

G. A. Molander (Philadelphia, USA)

P. J. Reider (Princeton, USA)

E. Schaumann (Clausthal-Zellerfeld, Germany)

M. Shibasaki (Tokyo, Japan)

E. J. Thomas (Manchester, UK)

B. M. Trost (Stanford, USA)

Abstracts

1.7 Product Class 7: Organometallic Complexes of Iron

G. R. Stephenson

This chapter is a revision of the previous Science of Synthesis contribution describing methods for the synthesis of organometallic complexes of iron with hapticities between η6(arene complexes) and η1 (carbene complexes and σ-bonded complexes).

The main methods surveyed are the direct complexation of ligands, nucleophile addition to cationic complexes (which reduces the hapticity by one), protonation of unsaturated but non-coordinated sections of ligands or ligands bearing leaving groups (which increases the hapticity by one), and functional-group transformations of substituents on the haptyl ligand (which leaves the hapticity unchanged). Access to nonracemic complexes and the use of iron complexes in total synthesis are discussed.

Keywords: iron complexes · arene complexes · cyclohexadienyl complexes · diene complexes · π-allyl complexes · alkene complexes · alkyne complexes · metal–carbene complexes · carbonyl complexes · nucleophilic addition · regioselectivity · diastereoselectivity · asymmetric synthesis · enantioselectivity · enantiomeric resolution · kinetic resolution · total synthesis

1.7.8.17 Ferrocenes

G. R. Stephenson

This chapter is an update to the earlier Science of Synthesis Section 1.7.8 describing methods for the synthesis of ferrocenes. The focus is on the literature published between 2000 and early 2013. The main methods discussed are direct complexation of ligands, modification of cyclopentadienyl rings by electrophilic substitution or directed lithiation, and functional-group transformations in ferrocenyl side-chains. The access to nonracemic ferrocenes and to ferrocenes with configurationally defined side-chain chirality is discussed.

Keywords: iron complexes · ferrocenes · cyclopentadienyl complexes · acylation · lithiation · materials synthesis · bioorganometallic chemistry · diastereoselectivity · asymmetric synthesis · enantioselectivity · enantiomeric resolution · kinetic resolution · asymmetric catalysis

3.1.11 Organometallic Complexes of Zinc

X.-F. Wu

Zinc salts are abundant, inexpensive, nontoxic, and exhibit environmentally benign properties. As a result, organic chemists have been interested in using zinc salts as catalysts in organic synthesis during the last three decades. In this chapter, the main contributions on zinc-catalyzed organic synthesis are summarized and discussed. Many name reactions with zinc as catalyst are included, as well as zinc-catalyzed reduction and oxidation reactions.

Keywords: zinc catalysts · organic synthesis · asymmetric synthesis · C—C bond formation · C—N bond formation · C—O bond formation · reduction · oxidation

4.4.46 Product Subclass 46: Siloles

J. Kobayashi and T. Kawashima

This chapter describes methods for the synthesis of siloles and benzannulated analogues (benzosiloles and dibenzosiloles). Classical routes to siloles involve the nucleophilic attack of a carbanion onto the silicon atom, but more recent developments involving different approaches are included as well.

Keywords: siloles · benzosiloles · dibenzosiloles · reductive cyclization · C—C bond formation · transmetalation

20.5.9.2 2,2-Diheteroatom-Substituted Alkanoic Acid Esters

T. L. March and P. J. Duggan

This chapter is an update to the earlier Science of Synthesis contribution describing methods for the preparation of 2,2-diheteroatom-substituted alkanoic acid esters, and covers the literature published in the period 2007–2012. A major focus has been on the development of stereoselective Reformatsky and conjugate addition reactions, while atom-transfer radical addition and cyclization methods continue to attract strong interest.

Keywords: carbon—halogen bonds · carbon—heteroatom bonds · chlorination · conjugate addition · coumarins · esters · fluorine compounds · Friedel–Crafts acylation · haloalkylation · halogenation · hetero-Diels–Alder reaction · atom-transfer radical addition · atom-transfer radical cyclization · Reformatsky reaction

26.8.4 Aryl Ketones

J. D. Sellars

This chapter is an update to the earlier Science of Synthesis contribution describing methods for the synthesis of aryl ketones. It focuses on the literature published in the period 2003–2013.

Keywords: aryl ketones · arynes · C—H activation · Friedel–Crafts acylation · Fries rearrangement · hydroacylation · organometallic reagents · supported catalysis

Science of Synthesis Knowledge Updates 2014/1

Preface

Abstracts

Table of Contents

1.7 Product Class 7: Organometallic Complexes of Iron

G. R. Stephenson

1.7.8.17 Ferrocenes (Update 2014)

G. R. Stephenson

3.1.11 Organometallic Complexes of Zinc (Update 2014)

X.-F. Wu

4.4.46 Product Subclass 46: Siloles

J. Kobayashi and T. Kawashima

20.5.9.2 2,2-Diheteroatom-Substituted Alkanoic Acid Esters (Update 2014)

T. L. March and P. J. Duggan

26.8.4 Aryl Ketones (Update 2014)

J. D. Sellars

Author Index

Abbreviations

Table of Contents

Volume 1: Compounds with Transition Metal–Carbon π-Bonds and Compounds of Groups 10 – 8 (Ni, Pd, Pt, Co, Rh, Ir, Fe, Ru, Os)

1.7 Product Class 7: Organometallic Complexes of Iron

G. R. Stephenson

1.7 Product Class 7: Organometallic Complexes of Iron

1.7.1 Product Subclass 1: Iron–Arene Complexes

Synthesis of Product Subclass 1

1.7.1.1 Method 1: Direct Complexation of Arenes

1.7.1.2 Method 2: Iron-Catalyzed Cycloaromatization

1.7.1.3 Method 3: Modification of η6-Complexes

1.7.1.3.1 Variation 1: Replacement of Chloride in Chlorobenzene Complexes by Nucleophiles

1.7.1.3.2 Variation 2: Use of Palladium-Catalyzed Coupling in the Presence of Cationic Iron–Cyclopentadienyl Complexes

1.7.1.3.3 Variation 3: Use of Nucleophilic Complexes Obtained by Deprotonation of Arene–Cyclopentadienyliron Complexes

1.7.1.3.4 Variation 4: Ligand Modification by Ring-Closing Metathesis

1.7.1.3.5 Variation 5: Nucleophile Addition to a Carbonyl Ligand

1.7.1.3.6 Variation 6: Modification of Functional Groups in the Presence of Cationic Iron–Cyclopentadienyl Complexes

Applications of Product Subclass 1 in Organic Synthesis

1.7.1.4 Method 4: Metal Removal To Give Organic Products

1.7.2 Product Subclass 2: Iron–Dienyl Complexes

Synthesis of Product Subclass 2

1.7.2.1 Method 1: Direct Complexation

1.7.2.1.1 Variation 1: Reaction of Cyclopentadienyl Anions with Iron Salts

1.7.2.1.2 Variation 2: Transfer of Cyclopentadienyliron

1.7.2.1.3 Variation 3: From Neutral Cyclopentadiene Derivatives

1.7.2.2 Method 2: Modification of η5-Cyclopentadienyl Complexes

1.7.2.2.1 Variation 1: Friedel–Crafts Acylation of Ferrocene Complexes

1.7.2.2.2 Variation 2: Metalation of Ferrocene Complexes

1.7.2.2.3 Variation 3: Modification of Functional Groups on Ferrocene Complexes

1.7.2.2.4 Variation 4: Redox Chemistry at the Metal of Ferrocene Complexes

1.7.2.2.5 Variation 5: Protonation at Iron

1.7.2.2.6 Variation 6: Manipulation of Di-μ-carbonyldicarbonylbis (η5-cyclopentadienyl)diiron

1.7.2.3 Method 3: Preparation by Hydride Abstraction

1.7.2.3.1 Variation 1: Regioisomer Preparation without Rearrangement

1.7.2.3.2 Variation 2: Regioisomer Preparation with Rearrangement

1.7.2.4 Method 4: Preparation from η4-Triene Complexes with Electrophiles

1.7.2.5 Method 5: Preparation from Dienol Complexes with Acid

1.7.2.5.1 Variation 1: Without Rearrangement

1.7.2.5.2 Variation 2: With Rearrangement

1.7.2.6 Method 6: Preparation by Demethoxylation in Acid

1.7.2.7 Method 7: Preparation by Oxidation with Thallium(III) Salts

1.7.2.8 Method 8: Preparation from Dienone Complexes

1.7.2.9 Method 9: Preparation from η6-Complexes

1.7.2.9.1 Variation 1: Nucleophile Addition to η6-Complexes at the π-System

1.7.2.9.2 Variation 2: Dealkoxylation of η6-Complexes

1.7.2.10 Method 10: Nucleophile Addition to η5-Complexes

1.7.2.10.1 Variation 1: Addition at the π-System

1.7.2.10.2 Variation 2: Addition next to the π-System

1.7.2.10.3 Variation 3: Addition at a Carbonyl Group

1.7.2.11 Method 11: Access to Salts by a Sequence of Nucleophile Addition and Leaving-Group Removal

1.7.2.11.1 Variation 1: Without Rearrangement

1.7.2.11.2 Variation 2: With Rearrangement

1.7.2.12 Method 12: Preparation by Opening Cyclopropane Rings

1.7.2.13 Method 13: Preparation of Nonracemic Complexes

1.7.2.13.1 Variation 1: From Ferrocene Complexes by Asymmetric Induction

1.7.2.13.2 Variation 2: From Complexes Originating from Resolution or Asymmetric Induction

1.7.2.13.3 Variation 3: From Complexes Originating from Biological Sources

Applications of Product Subclass 2 in Organic Synthesis

1.7.2.14 Method 14: Metal Removal To Give Organic Products

1.7.2.14.1 Variation 1: From Ferrocene Complexes

1.7.2.14.2 Variation 2: From Cationic η5-Ligated Tricarbonyliron Complexes

1.7.2.14.3 Variation 3: From η5-Cyclopentadienyl–Iron Complexes Formed by Nucleophilic Addition to η6-Complexes

1.7.3 Product Subclass 3: Iron–Diene Complexes

Synthesis of Product Subclass 3

1.7.3.1 Method 1: Preparation by Complexation

1.7.3.1.1 Variation 1: From Dienes without Rearrangement

1.7.3.1.2 Variation 2: From Dienes with Rearrangement

1.7.3.1.3 Variation 3: From Arenes by In Situ Reduction

1.7.3.1.4 Variation 4: From Dienes and Alkynes by Reaction with η1-Complexes

1.7.3.1.5 Variation 5: From Chromium Fischer Carbene Complexes

1.7.3.1.6 Variation 6: From Cycloheptatrienes and Cyclohexadienones by Reduction

1.7.3.1.7 Variation 7: From Dihydrothiophene 1,1-Dioxides

1.7.3.1.8 Variation 8: From Allyl Alcohols

1.7.3.1.9 Variation 9: From Dihalides, Allyl Halides, and Phosphate Esters

1.7.3.1.10 Variation 10: From Pyrones

1.7.3.1.11 Variation 11: From Dimethylcyclopropenes

1.7.3.1.12 Variation 12: From Vinylcyclopropanes

1.7.3.1.13 Variation 13: From Allenes via Trimethylenemethane Lactones

1.7.3.2 Method 2: Preparation from η3, η1-Complexes

1.7.3.2.1 Variation 1: From Ferralactone Complexes

1.7.3.2.2 Variation 2: From η3, η1-Complexes

1.7.3.2.3 Variation 3: Nucleophile Addition to Cationic η3, η1-Carbene Complexes

1.7.3.3 Method 3: Cyclodimerization of η2-Ligands

1.7.3.4 Method 4: Nucleophile Addition to η5-Complexes at the π-System

1.7.3.4.1 Variation 1: Cyclohexadienyl Complexes

1.7.3.4.2 Variation 2: Cycloheptadienyl Complexes

1.7.3.4.3 Variation 3: Cyclooctadienyl Complexes

1.7.3.4.4 Variation 4: Acyclic Dienyl Complexes

1.7.3.4.5 Variation 5: In Situ Generation of Acyclic Dienyl Complexes

1.7.3.4.6 Variation 6: Cyclopentadienyl Complexes

1.7.3.5 Method 5: Metal-Centered Reduction of η5-Complexes at the π-System

1.7.3.6 Method 6: Modification of η4-Complexes

1.7.3.6.1 Variation 1: By Acylation

1.7.3.6.2 Variation 2: By Lithiation and Addition of Electrophiles

1.7.3.6.3 Variation 3: By Palladium Coupling

1.7.3.6.4 Variation 4: Cyclization Reactions of η4-Diene Complexes

1.7.3.6.5 Variation 5: Oxidative Cyclization of η4-Diene Complexes

1.7.3.6.6 Variation 6: Nucleophile Addition to η4-Complexes at the π-System

1.7.3.6.7 Variation 7: Nucleophile Addition to η4-Complexes at a Carbonyl Ligand

1.7.3.6.8 Variation 8: Nucleophile Addition to η4-Complexes next to the π-System

1.7.3.6.9 Variation 9: Reactions of Enolates and Silyl Enol Ethers

1.7.3.6.10 Variation 10: Epoxide Formation and Cyclopropanation next to the π-System

1.7.3.6.11 Variation 11: Diol Synthesis next to the π-System

1.7.3.6.12 Variation 12: Epoxide Opening next to the π-System

1.7.3.6.13 Variation 13: Cycloaddition Reactions next to the π-System

1.7.3.6.14 Variation 14: By 1,3-Migration of a Tricarbonyliron Group

1.7.3.6.15 Variation 15: Functionalization of Cycloheptatriene Complexes

1.7.3.7 Method 7: Complexation of Heterodienes

1.7.3.8 Method 8: Additional Methods for the Formation of η4-Complexes

1.7.3.8.1 Variation 1: Alkylation of η3-Anions

1.7.3.8.2 Variation 2: From Pentacarbonyliron by Nucleophile Addition at Carbonyl

1.7.3.8.3 Variation 3: Exchange of Carbonyl for Phosphines, Phosphites, and Nitrosonium

1.7.3.8.4 Variation 4: Radical and Carbene Methods in the Presence of Iron Complexes

1.7.3.9 Method 9: Preparation of Nonracemic Complexes

1.7.3.9.1 Variation 1: Asymmetric Complexation

1.7.3.9.2 Variation 2: Asymmetric Modification and Kinetic Resolution of η4-Complexes

1.7.3.9.3 Variation 3: By Asymmetric Induction and Kinetic Resolution with η5-Complexes

1.7.3.9.4 Variation 4: Classical Resolution of Chiral η4-Complexes

1.7.3.9.5 Variation 5: Kinetic Resolution of Chiral η4-Complexes

Applications of Product Subclass 3 in Organic Synthesis

1.7.3.10 Method 10: Metal Removal To Give Organic Products

1.7.3.10.1 Variation 1: Decomplexation without Ligand Modification

1.7.3.10.2 Variation 2: Decomplexation with Ligand Modification

1.7.3.11 Method 11: Reactions next to η3-Complexes, Followed by Rearrangement 110

1.7.4 Product Subclass 4: Iron–Allyl Complexes

Synthesis of Product Subclass 4

1.7.4.1 Method 1: Protonation of Diene Complexes

1.7.4.1.1 Variation 1: From η2-Complexes

1.7.4.1.2 Variation 2: From η4-Complexes

1.7.4.1.3 Variation 3: During Direct Complexation of Allyl Alcohols and Dienes in the Presence of Acid

1.7.4.2 Method 2: Preparation by Leaving-Group Displacement from η2-Complexes

1.7.4.3 Method 3: Preparation by Opening Vinyl Epoxides and Cyclopropanes

1.7.4.3.1 Variation 1: From Epoxides

1.7.4.3.2 Variation 2: From Aziridines

1.7.4.3.3 Variation 3: From Cyclopropanes

1.7.4.3.4 Variation 4: From Cyclobutanes

1.7.4.4 Method 4: Nucleophile Addition at a Complexed π-System

1.7.4.4.1 Variation 1: Nucleophile Addition to η4-Complexes

1.7.4.4.2 Variation 2: Nucleophile Addition to η5-Complexes

1.7.4.4.3 Variation 3: Modification of Functionality and Ligand Exchange

1.7.4.5 Method 5: Nucleophile Addition to η3-Complexes next to the π-System

1.7.4.6 Method 6: Nucleophile Addition at a Carbonyl Ligand

1.7.4.6.1 Variation 1: Nucleophile Addition to η4-Complexes

1.7.4.6.2 Variation 2: Nucleophile Addition to η2, η2-Complexes

1.7.4.7 Method 7: Additional Methods for the Formation of η3-Complexes

1.7.4.7.1 Variation 1: Anionic η3-Complexes

1.7.4.7.2 Variation 2: Modification by Carbonyl Insertion

1.7.4.7.3 Variation 3: Modification by Alkene Insertion

1.7.4.7.4 Variation 4: From η4-Vinylketene Complexes

1.7.4.7.5 Variation 5: Reductive Methods To Make Anionic η3-Complexes

1.7.4.7.6 Variation 6: Exchange of Carbonyl for Nitrosonium

1.7.4.8 Method 8: Preparation of Nonracemic Complexes

Applications of Product Subclass 4 in Organic Synthesis

1.7.4.9 Method 9: Metal Removal To Give Organic Products

1.7.5 Product Subclass 5: Iron–Alkene Complexes

Synthesis of Product Subclass 5

1.7.5.1 Method 1: Direct Complexation of Alkenes

1.7.5.1.1 Variation 1: Ligand Exchange with a Butene Complex

1.7.5.1.2 Variation 2: Reaction with Nonacarbonyldiiron

1.7.5.1.3 Variation 3: Reaction with Pentacarbonyliron

1.7.5.2 Method 2: Preparation by Hydride Abstraction from η1-Complexes

1.7.5.3 Method 3: Preparation by Protonation of η1-Complexes

1.7.5.3.1 Variation 1: Protonation of η1-Allyl Complexes

1.7.5.3.2 Variation 2: Removal of Leaving Groups from η1-Alkyl Complexes

1.7.5.3.3 Variation 3: Protonation at Iron

1.7.5.4 Method 4: Reactions of η1-Allyl Complexes with Electrophiles

1.7.5.4.1 Variation 1: Reaction with Aldehydes and Ketones in the Presence of a Lewis Acid

1.7.5.4.2 Variation 2: Reaction with Activated Alkenes

1.7.5.4.3 Variation 3: Reaction with η2-Alkene Complexes

1.7.5.4.4 Variation 4: Reaction with η5-Dienyl Complexes

1.7.5.5 Method 5: Nucleophile Addition at a Complexed π-System

1.7.5.5.1 Variation 1: Nucleophile Addition to η2-Complexes

1.7.5.5.2 Variation 2: Nucleophile Addition to η3-Complexes

1.7.5.5.3 Variation 3: Nucleophile Addition to η4-Complexes

1.7.5.5.4 Variation 4: Nucleophile Addition to η5-Complexes

1.7.5.6 Method 6: Preparation of Nonracemic Complexes

Applications of Product Subclass 5 in Organic Synthesis

1.7.5.7 Method 7: Metal Removal To Give Organic Products

1.7.6 Product Subclass 6: Iron–Carbene Complexes

Synthesis of Product Subclass 6

1.7.6.1 Method 1: Preparation by the Fischer Carbene Method

1.7.6.2 Method 2: From Azadiene Iron Complexes

1.7.6.3 Method 3: Removal of Leaving Groups from Metal–Alkyl Complexes

1.7.6.4 Method 4: Formation of Iron–N-Heterocyclic Carbene Complexes

1.7.6.5 Method 5: Modification of Other Carbene Complexes

1.7.6.5.1 Variation 1: Exchange of Substituents at the Carbene Complex

1.7.6.5.2 Variation 2: Reaction at Functional Groups Adjacent to the Carbene Complex

1.7.6.5.3 Variation 3: Photolysis of Carbene Complexes

1.7.6.6 Method 6: Preparation by Ring Expansion

1.7.6.7 Method 7: Preparation of Bridging Carbene Complexes

1.7.6.8 Method 8: Reduction of Cationic μ-CH Bridging Carbyne Complexes

1.7.6.9 Method 9: Preparation of Nonracemic Complexes

Applications of Product Subclass 6 in Organic Synthesis

1.7.6.10 Method 10: Cyclopropanation by Transfer of Diazo Esters

1.7.6.11 Method 11: C—H Insertion Reactions

1.7.6.12 Method 12: Cyclization with Alkynes To Form Naphthols and Furans

1.7.6.13 Method 13: Removal of the Metal by Oxidation

1.7.7 Product Subclass 7: Iron–η1-Alkyl, -Alkenyl, -Alkynyl, and -Heteroatom-Bound Complexes

Synthesis of Product Subclass 7

1.7.7.1 Method 1: Metal Addition to Electrophiles

1.7.7.2 Method 2: Metal Addition to Nucleophiles/Lewis Bases

1.7.7.3 Method 3: Nucleophile Addition and Deprotonation Reactions

1.7.7.4 Method 4: Additional Methods for the Formation of η1-Alkyl Complexes

1.7.7.4.1 Variation 1: Nucleophile Addition to η1-Carbene Complexes

1.7.7.4.2 Variation 2: Nucleophile Addition to η2-Alkyne Complexes

1.7.7.4.3 Variation 3: Nucleophile Addition to Dicarbonyl(η5-cyclopentadienyl)iron Halides

1.7.7.4.4 Variation 4: Nucleophile Addition to Carbonyl Complexes

1.7.7.4.5 Variation 5: η1-Aryl and η1-Alkynyl Complexes by Catalyzed Coupling Reactions

1.7.7.4.6 Variation 6: η1-Alkynyl Complexes from Alkynes

1.7.7.4.7 Variation 7: Deprotonation of η2-Alkene Complexes

1.7.7.4.8 Variation 8: Introduction of Sulfur and Selenium to Di-μ-carbonyldicarbonylbis(η5-cyclopentadienyl)diiron

1.7.7.5 Method 5: Reactions of Allyl Complexes

1.7.7.5.1 Variation 1: η1-Allyl Complexes

1.7.7.5.2 Variation 2: η3-Allyl Complexes

1.7.7.6 Method 6: Modification of Ligands in η1-Complexes

1.7.7.7 Method 7: Preparation of Nonracemic Complexes

Applications of Product Subclass 7 in Organic Synthesis

1.7.7.8 Method 8: Oxidation of η1-Products

1.7.7.8.1 Variation 1: Metal Removal To Generate a Carboxylic Acid

1.7.7.8.2 Variation 2: Metal Removal To Generate an Ester

1.7.7.8.3 Variation 3: Metal Removal To Generate an Amide

1.7.7.8.4 Variation 4: Metal Removal To Generate Alkyl Bromides or Epoxides

1.7.7.8.5 Variation 5: Metal Removal To Generate Ketones and Lactones

1.7.7.8.6 Variation 6: Reactions as Arylating Agents

1.7.7.8.7 Variation 7: Metal Removal with Transmetalation to Mercury

1.7.7.9 Method 9: Additional Methods for Decomplexation of η1-Alkyl Complexes

1.7.7.9.1 Variation 1: Disproportionation of η1-Products

1.7.7.9.2 Variation 2: Photochemical Dimerization

1.7.7.9.3 Variation 3: Asymmetric Cycloaddition

1.7.7.10 Method 10: Formation and Reaction of Oxyallyl Cation Complexes

1.7.7.10.1 Variation 1: [4 + 3] Cycloaddition

1.7.7.10.2 Variation 2: [2 + 3] Cycloaddition

1.7.7.10.3 Variation 3: Electrophilic Substitution

1.7.7.11 Method 11: Application of Collman's Reagent and Related Tetracarbonylferrate Salts

1.7.7.11.1 Variation 1: Cyclization to Alkenes

1.7.7.11.2 Variation 2: Reductions with the Tetracarbonylhydroferrate Complex

1.7.8.17 Ferrocenes

G. R. Stephenson

1.7.8.17 Ferrocenes

1.7.8.17.1 Synthesis of Ferrocenes

1.7.8.17.1.1 Method 1: Monosubstituted and 1,1′-Disubstituted Ferrocenes by Metal-Mediated Procedures

1.7.8.17.1.1.1 Variation 1: Synthesis of Halogenated Ferrocenes

1.7.8.17.1.1.2 Variation 2: Synthesis of Hydroxy- and Alkoxyferrocenes and 1,1′-Dihydroxyferrocene

1.7.8.17.1.1.3 Variation 3: Synthesis of Aminoferrocenes and 1,1′-Diaminoferrocenes

1.7.8.17.1.1.4 Variation 4: Synthesis of Carboxyferrocene, Formylferrocene, 1,1′-Dicarboxyferrocene, and 1,1′-Diformylferrocene

1.7.8.17.1.1.5 Variation 5: Synthesis of 1′-Formyl-2,5-dimethylazaferrocene

1.7.8.17.1.2 Method 2: Acyl- and Alkenylferrocenes under Friedel–Crafts Conditions

1.7.8.17.1.2.1 Variation 1: Synthesis of Alkenylferrocenes and 1,1′-Dialkenylferrocenes

1.7.8.17.1.3 Method 3: Chiral Ferrocenylalkyl Alcohols and Ferrocenylalkylamines

1.7.8.17.1.3.1 Variation 1: Via Stereoselective Alkylation and Arylation of Formylferrocene

1.7.8.17.1.3.2 Variation 2: Via Stereoselective Reduction of Acyl Intermediates

1.7.8.17.1.3.3 Variation 3: Via Enzymatic Methods

1.7.8.17.1.4 Method 4: Oxazol-2-ylferrocenes

1.7.8.17.1.5 Method 5: Chiral Ferrocenyl Aminals

1.7.8.17.1.6 Method 6: Chiral Ferrocenyl Sulfoxides

1.7.8.17.1.7 Method 7: Chiral 1,2-Disubstituted Ferrocenes by Diastereoselective Functionalization

1.7.8.17.1.7.1 Variation 1: From 1-Ferrocenyl-N,N-dimethylethylamine

1.7.8.17.1.7.2 Variation 2: From (4,5-Dihydrooxazol-2-yl) ferrocenes

1.7.8.17.1.7.3 Variation 3: From Chiral Ferrocenyl Acetals and Aminals

1.7.8.17.1.7.4 Variation 4: From Chiral Ferrocenyl Sulfoxides

1.7.8.17.1.8 Method 8: C—C Bond Formation by Substitution of Ferrocenyl Alcohols

1.7.8.17.1.9 Method 9: Cross-Coupling Reactions of Iodoferrocene and Ferrocenylboronic Acid

1.7.8.17.1.10 Method 10: Chiral 1,2-Disubstituted Ferrocenes via Enantioselective Sparteine-Mediated Lithiation

1.7.8.17.1.11 Method 11: 1,1′,2-Trisubstituted Ferrocenes (BPPF-Type Ligands)

1.7.8.17.1.12 Method 12: Tetrasubstituted Ferrocenes from 1,1′-Bis(1-methoxyalkyl) ferrocenes

1.7.8.17.1.13 Method 13: Chiral Biferrocenes

1.7.8.17.2 Applications of Ferrocenes in Organic Synthesis

1.7.8.17.2.1 Method 1: Catalytic Enantioselective Hydrogenation

1.7.8.17.2.2 Method 2: Catalytic Enantioselective Hydroboration

1.7.8.17.2.3 Method 3: Catalytic Enantioselective Hydrosilylation

1.7.8.17.2.4 Method 4: Catalytic Enantioselective Allylic Substitution

1.7.8.17.2.5 Method 5: Catalytic Enantioselective Aldol Reactions

1.7.8.17.2.6 Method 6: Diethylzinc Addition to Aldehydes

1.7.8.17.2.7 Method 7: Michael Addition Reactions

1.7.8.17.2.8 Method 8: Asymmetric Arylation of Aldehydes

1.7.8.17.2.9 Method 9: Metal-Catalyzed [3 + 2] Cycloaddition

1.7.8.17.2.10 Method 10: Ring Opening of Azabenzonorbornadienes

1.7.8.17.2.11 Method 11: Applications as Bioactives

1.7.8.17.2.12 Method 12: Applications as Bioconjugates

1.7.8.17.2.13 Method 13: Applications in Electron Reservoirs and in Nonlinear Optics (NLO)

1.7.8.17.2.14 Method 14: Applications in Oligomers and Polymers

1.7.8.17.2.15 Method 15: Applications as Functional Devices

Volume 3: Compounds of Groups 12 and 11 (Zn, Cd, Hg, Cu, Ag, Au)

3.1 Product Class 1: Organometallic Complexes of Zinc

3.1.11 Organometallic Complexes of Zinc

X.-F. Wu

3.1.11 Organometallic Complexes of Zinc

3.1.11.1 Zinc-Catalyzed Organic Transformations

3.1.11.1.1 Method 1: Zinc-Catalyzed C—C Bond-Forming Reactions

3.1.11.1.1.1 Variation 1: Zinc-Catalyzed Aldol Reaction

3.1.11.1.1.2 Variation 2: Zinc-Catalyzed Henry Reaction

3.1.11.1.1.3 Variation 3: Zinc-Catalyzed Mannich Reaction

3.1.11.1.1.4 Variation 4: Zinc-Catalyzed Michael Reaction

3.1.11.1.1.5 Variation 5: Zinc-Catalyzed Friedel–Crafts Reactions

3.1.11.1.1.6 Variation 6: Zinc-Catalyzed Alkynylation Reactions

3.1.11.1.1.7 Variation 7: Other Zinc-Catalyzed C—C Bond-Forming Reactions

3.1.11.1.2 Method 2: Zinc-Catalyzed C—N Bond-Forming Reactions

3.1.11.1.3 Method 3: Zinc-Catalyzed C—O Bond-Forming Reactions

3.1.11.1.4 Method 4: Zinc-Catalyzed Reduction Reactions

3.1.11.1.5 Method 5: Zinc-Catalyzed Oxidation Reactions

Volume 4: Compounds of Group 15 (As, Sb, Bi) and Silicon Compounds

4.4 Product Class 4: Silicon Compounds

4.4.46 Product Subclass 46: Siloles

J. Kobayashi and T. Kawashima

4.4.46 Product Subclass 46: Siloles

Synthesis of Product Subclass 46

4.4.46.1 Ring Synthesis from Acyclic Compounds

4.4.46.1.1 Method 1: Formation of One Si—C Bond of the Silole

4.4.46.1.1.1 Variation 1: Nucleophilic Addition of a Carbanion to the Silicon Atom

4.4.46.1.1.2 Variation 2: Intramolecular Hydrosilylation of Alkynes

4.4.46.1.1.3 Variation 3: Reductive Cyclization of Alkynes

4.4.46.1.1.4 Variation 4: Nucleophilic Addition of a Silyl Anion to Alkynes

4.4.46.1.1.5 Variation 5: Electrophilic Substitution of an Aromatic Ring with a Silyl Cation

4.4.46.1.1.6 Variation 6: Rhodium-Catalyzed Intramolecular trans-Bis-silylation of Alkynes

4.4.46.1.1.7 Variation 7: Gold-Catalyzed Intramolecular trans-Allylsilylation of Alkynes

4.4.46.1.1.8 Variation 8: Palladium-Catalyzed Intramolecular C(sp2)—Si Coupling via Cleavage of a C(sp3)—Si Bond

4.4.46.1.2 Method 2: Formation of C—C Bonds of the Silole

4.4.46.1.2.1 Variation 1: Reductive Cyclization of Dialkynylsilanes

4.4.46.1.2.2 Variation 2: Intramolecular Cross-Coupling Reaction of Diarylsilanes

4.4.46.1.2.3 Variation 3: Iridium-Catalyzed [2 + 2 + 2] Cycloaddition of Silicon-Bridged Diynes with Alkynes

4.4.46.1.2.4 Variation 4: Ring-Closing Metathesis of Alkenyl(2-alkenylphenyl) silanes

4.4.46.1.3 Method 3: Formation of Two Si—C Bonds of the Silole

4.4.46.1.3.1 Variation 1: Nucleophilic Attack of Dianions at the Silicon Atom

4.4.46.1.3.2 Variation 2: Transmetalation of Zirconium-Containing Metallacycles

4.4.46.1.3.3 Variation 3: Ruthenium-Catalyzed Double Hydrosilylation of Buta-1,3-diynes

4.4.46.1.4 Method 4: Formation of One Si—C and One C—C Bond of the Silole

4.4.46.1.4.1 Variation 1: Rhodium-Catalyzed Coupling of (2-Silylphenyl) boronic Acids with Alkynes

4.4.46.1.4.2 Variation 2: Palladium-Catalyzed Intermolecular Coupling of 2-Silylaryl Bromides with Alkynes

4.4.46.1.5 Method 5: Formation of Two Si—C Bonds and One C—C Bond of the Silole

4.4.46.1.5.1 Variation 1: Palladium-Catalyzed Coupling of Silylboronic Esters with Alkynes

4.4.46.1.6 Method 6: Rearrangement of a Rhodium–Alkene Complex

4.4.46.2 Ring Synthesis by Transformation from Another Ring System

4.4.46.2.1 Method 1: Ring Expansion of Silirenes

20.5 Product Class 5: Carboxylic Acid Esters

20.5.9.2 2,2-Diheteroatom-Substituted Alkanoic Acid Esters

T. L. March and P. J. Duggan

20.5.9.2 2,2-Diheteroatom-Substituted Alkanoic Acid Esters

20.5.9.2.1 Method 1: Formation from β, γ-Unsaturated α-Oxo Esters

20.5.9.2.2 Method 2: Formation from α-Sulfanyl and α-Thioxo Esters

20.5.9.2.2.1 Variation 1: Thia-Diels–Alder Reactions of Dithiooxalates

20.5.9.2.2.2 Variation 2: Desulfurizing Difluorination of 2-Sulfanylacetates

20.5.9.2.3 Method 3: Formation of 2,2-Dinitrogen-Substituted Esters

20.5.9.2.3.1 Variation 1: Formation of 2,2-Dinitrogen-Substituted Esters by Displacement of Halide

20.5.9.2.3.2 Variation 2: Formation of 2,2-Dinitrogen-Substituted Esters by Addition to α, β-Unsaturated Esters

20.5.9.2.3.3 Variation 3: Formation of 2,2-Dinitrogen-Substituted Esters by Addition to Imino- and Azocarboxylates

20.5.9.2.3.4 Variation 4: Formation of 2,2-Dinitrogen-Substituted Esters by α-Nitration of Esters

20.5.9.2.4 Method 4: Formation by Halogenation of β-Oxo Esters

20.5.9.2.5 Method 5: Formation by Nucleophilic Attack of the α-Carbon of Alkanoic Acid Esters

20.5.9.2.5.1 Variation 1: Metal-Mediated C—C Bond Formation from Trihaloacetates and 2,2-Difluoro-2-silylacetates

20.5.9.2.5.2 Variation 2: Nucleophilic Substitution at the α-Carbon of Dihaloacetates or Diheteroatom-Substituted Ketene Silyl Acetals

20.5.9.2.5.3 Variation 3: Nucleophilic Substitution of Alkyl Chloroformates

20.5.9.2.6 Method 6: Formation of α,α-Dihalo Esters by Radical-Mediated Transformations

20.5.9.2.7 Method 7: Difluorination of Acid Chlorides

Volume 26: Ketones

26.8 Product Class 8: Aryl Ketones

26.8.4 Aryl Ketones

J. D. Sellars

26.8.4 Aryl Ketones

26.8.4.1 Synthesis from Arenes

26.8.4.1.1 Friedel–Crafts Acylation

26.8.4.1.1.1 Method 1: Acylation Using Acid Chlorides or Anhydrides

26.8.4.1.1.1.1 Variation 1: With p-Block Metal Catalysts

26.8.4.1.1.1.2 Variation 2: With Transition-Metal Catalysts

26.8.4.1.1.1.3 Variation 3: With Lanthanides and Actinides

26.8.4.1.1.1.4 Variation 4: With Solid-Supported Catalysts

26.8.4.1.1.1.5 Variation 5: With Brønsted Acid Catalysts

26.8.4.1.1.2 Method 2: Acylation Using Carboxylic Acids

26.8.4.1.1.3 Method 3: Acylation Using Esters

26.8.4.2 Synthesis from Arylmetals

26.8.4.2.1 Method 1: Synthesis from Arenes via C—H Activation

26.8.4.2.2 Method 2: Synthesis from Arylboron Reagents

26.8.4.2.2.1 Variation 1: With Acid Chlorides or Anhydrides

26.8.4.2.2.2 Variation 2: With Esters

26.8.4.2.2.3 Variation 3: With Nitriles

26.8.4.2.2.4 Variation 4: With Aldehydes

26.8.4.2.3 Method 3: Synthesis from Carboxylic Acids

26.8.4.2.4 Method 4: Synthesis from Sulfinic Acids

26.8.4.3 Synthesis from Aryl Halides

26.8.4.3.1 Method 1: Synthesis via Organometallic Reagents

26.8.4.3.1.1 Variation 1: With Amides

26.8.4.3.1.2 Variation 2: With Acid Chlorides

26.8.4.3.1.3 Variation 3: With Vinyl Ethers/Acetates/Enamines/Enamides

26.8.4.3.1.4 Variation 4: With Hydrazones

26.8.4.3.2 Method 2: Carbonylation

26.8.4.4 Synthesis from Acyl Anion Equivalents

26.8.4.5 Synthesis via Oxidation

26.8.4.5.1 Method 1: Oxidation of Benzylic Alcohols

26.8.4.5.2 Method 2: Oxidation of Aryl Methylenes

26.8.4.6 Synthesis via Rearrangement

26.8.4.6.1 Method 1: Fries Rearrangement

26.8.4.6.2 Method 2: Alkyne Hydration/Rearrangement

26.8.4.7 Synthesis via Cycloaddition of Arynes

Author Index

Abbreviations

1.7 Product Class 7: Organometallic Complexes of Iron

G. R. Stephenson

General Introduction

This chapter supersedes the original ▶ Section 1.7 of Science of Synthesis, taking into account the literature published since 2000. Previously published information regarding this product class can be found in Houben–Weyl, Vol. 13/9a, pp 175–523. In ▶ Section 1.7, the chemistry of organometallic complexes of iron, with emphasis on their use as intermediates in organic synthesis, is surveyed.

The complexation of ligands, typically unsaturated hydrocarbons, dramatically alters the chemistry of the organic moiety, stabilizing structures that would otherwise be impossible to isolate, and, conversely, imparting reactivity on structures that are normally relatively unreactive. Often the reactivity of the metal complex is different from, and complementary to, the chemistry of the free ligand. Iron complexes of ligands ranging from η6 to η1 now have varied uses as intermediates in synthesis, and the reactivity patterns in the iron series follow those of complexes of other transition metals discussed elsewhere in Science of Synthesis. Because iron has the ability to stabilize a positive charge in π-complexes, reactions of π-bound ligands with nucleophiles make up the most generally used class of reactions in organoiron chemistry, providing valuable bond-forming procedures across the series η6 to η2, and typically forming products with hapticity one less than the starting material, as cationic electrophilic π-complexes tend to react at the terminus of the metal-bound portion of the ligand. (In Science of Synthesis, reactions are classified according to the products formed, therefore these reactions will be found in the sections describing the preparation of η5- to η1-structures.) Reactions with nucleophiles at internal positions produce structures with lower hapticity. In common with other organotransition-metal structures, organoiron complexes with η1-ligands exhibit σ-bond migrations to π-bound ligands and pairs of π-bound ligands can combine within the coordination sphere of the metal. These processes are typical of neutral structures of relatively low hapticity.

The subject area of ▶ Section 1.7 is similar to that of two far more extensive reviews of mononuclear iron complexes with hydrocarbon ligands, covering the periods through to 1981,[1–3] and between 1982 and 1994,[4] and citing over 2000 references; these have been followed by surveys of uses of iron complexes in synthesis in 1999[5,6] and 2000[7] for stoichiometric methods, and 2000[8] and 2004[9] for catalytic procedures. Information on specific compounds [e.g., pentacarbonyliron,[10] nonacarbonyldiiron,[11] (η4-benzylideneacetone) tricarbonyliron,[12] tricarbonyl(cyclobutadiene)iron,[13] tricarbonyl(cyclohexadiene)iron,[14] and tricarbonyl(cyclohexadienyl)iron tetrafluoroborate[15]] is also available in the Encyclopedia of Reagents for Organic Synthesis.

The history of the discovery of ferrocene has been reviewed,[16] and the first 50 years of the development of ferrocene chemistry was celebrated in a special article in 2002.[17] Ferrocene chemistry is described comprehensively in a classic series of annual surveys by Rockett and Marr up to 1989,[18] and in 2008 in a compilation edited by Štěpnička.[19] Iron fullerene complexes were reviewed in 1999.[20] There are also more recent surveys of specific classes of ferrocene-containing compounds, e.g. ferrocenophanes,[21] ferrocenyl heterocycles,[22] ferrocenes as rotary modules for molecular machines,[23] and polymers[24] (including liquid-crystalline polymers,[25] dendrimers,[26,27] and multichannel molecular receptors for cations and anions[28]) (see ▶ Sections 1.7.8.17.2.14 and 1.7.8.17.2.15). There is also a detailed Encyclopedia of Reagents for Organic Synthesis entry for ferrocene, as well as many ferrocenyl derivatives, by Pauson.[29]

Work on ferrocene synthesis directed toward the preparation of new classes of chiral amine and phosphine ligand structures, as well as molecules designed for the needs of materials science, in which ferrocene is incorporated in the final structure for functional effect, has also been reviewed.[30,31] The key aspect of enantioselective synthesis of multiply substituted ferrocenes has grown in importance over the years, and was reviewed in 2008,[32] 2009,[33,34] 2010,[35] and 2013.[36] Ligand classes with mixed planar and atom-centered chirality[37] and biferrocene-based ligands[38] have also been surveyed. The applications of chiral ferrocenyl ligands have been summarized.[39–42] There is also a more recent review (2010) on metallocyclic ferrocenyl ligands.[43]

▶ Section 1.7.8.17.2.12 gives examples of the uses of ferrocenyl compounds in biology. This relatively new topic has already been the subject of several reviews, including those on antitumor ferrocenes,[44] ferrocenyl conjugates of amino acids, peptides, and nucleic acids,[45–47] modulation of estrogen receptors,[48] and antimalarials.[49,50] The bioorganometallic chemistry of ferrocene was described in Chemical Reviews in 2004,[51] and the medicinal chemistry of ferrocenes was discussed in 2007.[52] The more general use of ferrocene derivatives in analytical chemistry was surveyed in 2008.[53]▶ Sections 1.7.8.17.2.4, 1.7.8.17.2.12, and 1.7.8.17.2.15 give examples of “click” chemistry involving ferrocene-containing components. The importance of this convenient strategy was reviewed in 2011.[54]

The tricarbonyliron chemistry of cyclic ligands was reviewed by Pearson[55] and Knölker,[56] and that of the acyclic ligands was covered by Grée[57,58] and Donaldson,[59,60] and also by Ong,[61] Thomas,[62] and Danks,[63] who reviewed the chemistry of tricarbonyliron triene complexes, vinylketene, vinylketenimine, and vinylallene complexes, and azadiene complexes, respectively. Enders and co-workers have reviewed iron-mediated allylic substitution.[64] Ley has surveyed ferralactone chemistry,[65] and Knölker has reviewed the use of azadiene complexes to prepare non-racemic tricarbonyliron diene complexes.[66] The photochemistry of iron sandwich complexes, discussed in ▶ Section 1.7.1.4 as a method to remove η6-ligands, has been reviewed by Astruc.[67]

Iron acyl chemistry has been reviewed by Davies.[68] New organic synthetic methods using iron carbonyl reagents were reviewed in 2000,[8] updating a summary of applications of dicarbonyl(cyclopentadienyl) ferrates collated by Rück-Braun in 1997.[69] Annual surveys of organoiron chemistry were presented until the early 1990s,[70] and in 2006[71] and 2011[72] summaries on this topic were published in the Encyclopedia of Inorganic Chemistry. There are numerous older or more specialized reviews and classic books[73] on the organic chemistry of iron.

Ferrocene does not hold the monopoly in organoiron chemistry for use in dendrimers or in bioanalysis (see above). The use of η6-ligands in dendrimer synthesis,[74] and carbonyliron complexes in analytical chemistry,[75] have also been the subject of reviews since the original version of ▶ Section 1.7 was published. The synthetic applications of cationic iron (and cobalt) carbonyl complexes were reviewed in 2009,[76] and the regiocontrol of the addition of nucleophiles to cationic organoiron complexes (see ▶ Sections 1.7.1.3.1, 1.7.2.9.1, 1.7.2.10, 1.7.4.4, and 1.7.5.5) has been categorized and related to a general description for a range of metal ligand systems in a chapter in Knochel's Handbook of Functionalized Organometallics (2005).[77]

The chirality of iron complexes follows the general pattern[78] of planar chirality of substituted organotransition-metal π-complexes. In the η6- to η2-series, a wide range of substitution patterns affords chiral structures and the stereochemical consequences of planar chirality in organoiron complexes is general across the η6- to η2-series. The metal typically imparts complete stereocontrol in the reactions at the coordinated ligand, so that chirality in the complex can be relayed perfectly to new stereogenic centers built in the ligand by the metal-mediated reaction. Direct nucleophile attack on electrophilic ligands proceeds “exo” (on the face opposite to the face of the ligand that carries the metal) while migration of ligands to the π-bound ligand has “endo” stereocontrol. Because the ligands in the planar-chiral η6-to η2-structures are unsymmetrically substituted, the regiocontrol of their reactions is an important issue, and there are consistent patterns of regioselectivity across the η6- to η2-series of organoiron structures, which correspond to the general control effects for transition-metal π-complexes.[79]

The range of structures discussed in ▶ Section 1.7 is wide (see ▶ Scheme 1), with π-complexes represented by hapticities from η6 to η1 (carbene), and a selection of σ-bonded structures, many of which also contain π-bonded regions to the same ligand. Because catalytic procedures are dealt with elsewhere in Science of Synthesis (classified in the sections dealing with the corresponding product class), the survey presented here is largely restricted to stoichiometric reactions. This need not make this the “second-best” chemistry for applications in organic synthesis if targets with several stereogenic features are addressed. When powerfully stereodirecting metal complexes are used stoichiometrically, they can impose diastereoselectivity on a series of reaction steps during a synthesis. Benefit is gained each time the metal is used. This approach is well represented in the σ-bonded ligand classes by the extensive synthetic utilization of the Davies/Liebeskind chiral iron–acyl complexes (see ▶ Sections 1.7.6.9, 1.7.7.4.4, and 1.7.7.7) in sequential elaborations that progressively build up a product structure, and in π-complexes by reaction sequences that exploit electrophilic organometallic structures in a series of reactions with nucleophiles. Each time a nucleophile adds to a π-complex, the extent of hapticity is reduced, and the charge changes. Thus, a cationic ηn-electrophile becomes a neutral η(n–1)-product. For an extended series of nucleophile additions, reactivation is needed, either by the cationic ηn-form being re-formed or by the metal–ligand assembly being modified, to change the charge on the metal without reversion to the original hapticity. The first is an iterative process, and the second is a linear process.[80]

▶ Scheme 1 Hapticity/Isoelectronic Relationships in Selected Organoiron Complexes

▶ Scheme 2 Related Structural Types in the Organoiron Series

An advantage of sequences of nucleophile addition, followed later by a reactivation step, is that the less-electrophilic forms can be present during the modification of adjacent functionality, or simply carried through conventional synthetic steps elsewhere in the molecule. Switching between powerfully electrophilic forms and less-reactive neutral structures introduces flexibility when sequences of metal-mediated steps are devised. This chemistry is firmly established and can be used with confidence at stages in the synthetic route where neutral (and hence only weakly electrophilic) π-complexes are present.

▶ Scheme 3 Range of Cationic Organoiron Complexes, with Possible Regiodirecting Substituents[82–84]

In summary, powerful directing effects influence regio- and stereocontrol in the chemistry of organoiron π-complexes, and σ-bonded structures exhibit a useful range of insertion reactions. These properties have been exploited successfully in target-molecule synthesis (see ▶ Sections 1.7.1.4, 1.7.2.14, 1.7.3.10, 1.7.3.11, 1.7.4.9, 1.7.5.7, 1.7.6.10–1.7.6.13, and 1.7.7.8) and, in some cases, methods have been demonstrated in which repeated use of the metal has been achieved. Often the organoiron complexes need no chiral auxiliary ligands, as they possess planar chirality, yet this stereochemical feature dominates the outcome of many bond-forming reactions. Methods are available for obtaining them in nonracemic form (see ▶ Sections 1.7.2.13, 1.7.3.9, 1.7.4.8, 1.7.5.6, 1.7.6.9, and 1.7.7.7). Not all the metal complexes discussed in this section have the extreme stability needed for use in multistep synthesis, but many are amongst the most stable organometallic structures known and play a worthwhile role in synthetic procedures that give rise to an extensive selection of organic target molecules.

SAFETY:

Handling pentacarbonyliron requires care as this is a volatile, toxic substance, and the heavy vapor released into the air following a spillage is hard to contain in standard extraction facilities. The solid reagents nonacarbonyldiiron and dodecacarbonyltriiron present less of a problem because they are not volatile, though care must be taken concerning dust (particularly with nonacarbonyldiiron which is prepared as a light, flaky substance), and it should be remembered that reactions using nonacarbonyldiiron (and to a lesser extent other carbonyliron reagents) form pentacarbonyliron as a reaction byproduct, and this necessitates care in the workup procedures. Waste carbonyliron reagents can be quenched with bromine in glacial acetic acid. This process is vigorous, producing copious fumes, and should only be performed cautiously when working on scales above 1 gram. In the event of a spillage and exposure to pentacarbonyliron, it is advisable to seek medical help, since, if the exposure proves to have been severe, the onset of breathing difficulties can be some hours after the incident, perhaps during the night when immediate assistance is unavailable. These hazards, however, should be put into perspective. Many large research teams around the world have routinely handled carbonyliron reagents throughout the history of the development of this chemistry, even using pentacarbonyliron on 100-gram scales in unmodified high-efficiency fume cupboards (linear extraction rate >0.5 m·s–1, 50-cm sash opening), without unacceptable risks, and the chemistry of the neutral organoiron complexes and their electrophilic cationic derivatives has been explored over this time by hundreds of scientists, without encountering significant safety scares. The key to safe utilization is the correct training of investigators in the manipulation of the primary carbonyls themselves and, in particular, the availability of clear instructions setting out the procedure in the event of a spillage.

1.7.1 Product Subclass 1: Iron–Arene Complexes

The η6-arene complexes of iron are valued in organic synthesis because cationic examples react well with nucleophiles. The normal electrophilic substitution reactions of arenes are replaced by reactions in which the arene complexes themselves serve as the electrophiles (see ▶ Sections 1.7.1.3.1 and 1.7.2.9.1). FeCp is commonly used to denote Fe(η5-C5H5), while Fe(Cp*) denotes Fe(η5-C5Me5).

Synthesis of Product Subclass 1

1.7.1.1 Method 1: Direct Complexation of Arenes

The most widely used method of preparing η6-arene complexes of iron by direct complexation employs aluminum trichloride with iron salts or cyclopentadienyliron complexes including ferrocene (1). Reaction of hexamethylbenzene with iron(II) chloride and aluminum trichloride affords the dicationic bis-η6-arene complex [Fe(C6Me6)2](PF6)2, after ammonium hexafluorophosphate has been added to exchange counterions.[85] The product can be reduced with sodium amalgam to complete an improved route to a neutral 20-electron [Fe(C6Me6)2] complex, which can, in turn, be converted by oxidation into a 19-electron monocationic salt [Fe(C6Me6)2]PF6.[86]

Compounds that contain both η6- and η5-hydrocarbon ligands are by far the most typical class of iron–arene complexes. These [FeCp(arene)]+ monocationic complexes are commonly prepared from ferrocene (1) (see ▶ Section 1.7.2.1), by the action of aluminum trichloride and aluminum powder. For example, chlorobenzene and ferrocene afford (η6-chlorobenzene)(η5-cyclopentadienyl)iron(II) hexafluorophosphate. Chlorotoluene complex 2 is obtained from 4-chlorotoluene and ferrocene (1) and is precipitated with ammonium tetrafluoroborate (▶ Scheme 4); use of ammonium hexafluorophosphate leads to the same complex with an alternative counterion.[87] Use of dry solvents is not necessary in these reactions, and in the case of the complexation of toluene, for example, addition of a small quantity of water improves efficiency. The preparation of an η6-complex from the bowl-shaped fused tetraarene sumanene 4 by the aluminum/aluminum trichloride method (▶ Scheme 4) provides the first example of an organoiron complex on the inner (concave) surface of the bowl.[88]

▶ Scheme 4 Complexation of Aromatic Ligands by Transfer of Cyclopentadienyliron from Ferrocene[87–89]

Other iron complexes containing η5-ligands can be used as precursors. For example, bromodicarbonyl(η5-pentamethylcyclopentadienyl)iron reacts with arenes and aluminum trichloride to afford arene π-complexes.[90] Similarly, a chiral analogue of the sumanene complex is prepared using (S,S)-1,1′-di-sec-butylferrocene.[91] Variation of the Lewis acid can give improved procedures in difficult cases, as in the complexation of phenanthrene. Whereas the dihydrophenanthrene complex is satisfactorily obtained by the normal aluminum trichloride procedure, much better results are obtained for phenanthrene if trichlorotrimethyldialuminum is used in place of aluminum trichloride.[92] Mononuclear η6-naphthalene complexes, e.g. 3 (▶ Scheme 4), can be prepared,[89,93] but under harsh conditions reduction to Tetralin complexes is possible.[89] Transfer of the FeCp group from [FeCp(η6-pyrene)]+ provides a solution to the problem of partial reduction. The pyrene complex itself is easily obtained by the normal aluminum/aluminum trichloride method.[94] This process is useful for simple arenes as well. For example, 1,2-dimethoxybenzene is converted into the cationic FeCp complex in 82% yield; with the corresponding 1,3-regioisomer, an excellent (98%) yield is possible. The method described above can also be applied to the preparation of (η5-cyclopentadienyl)(η6-fluorene)iron hexafluorophosphate.[95]

(η6-Arene)(η5-cyclopentadienyl)iron(II) Tetrafluoroborates, e.g. 2; General Procedure Using a Liquid Aromatic Ligand Precursor:[87]

CAUTION:

Aluminum trichloride dust is a severe irritant to all tissues and reacts violently with water.

Powdered anhyd AlCl3 (4.0 g, 30 mmol) and Al powder (0.35 g, 0.013 mol) were added to a soln of ferrocene (1; 3.0 g, 16 mmol), using an excess of the aromatic ligand (e.g., 4-chlorotoluene) as the solvent (50 mL). The mixture was refluxed under N2 for 6 h. The color of the soln changed from orange through pale green to red-brown. After the soln was cooled, H2O (150 mL) was slowly added, and the mixture was stirred vigorously for several min. The aqueous layer was separated and washed with petroleum ether to remove unchanged ferrocene, and then a slight excess of aq NH4BF4 was added. The precipitate was collected and purified by reprecipitation from acetone by addition of Et2O; this afforded the product (e.g., 2); yield: 2.2–3.2 g (40–60%); mp 200–203 °C. The corresponding hexafluorophosphate salts are prepared using sat. aq NH4PF6 in place of NH4BF4.

(η5-Cyclopentadienyl)(η6-naphthalene)iron(II) Hexafluorophosphate (3); Typical Procedure Using a Solid Aromatic Ligand Precursor:[89]

CAUTION:

Aluminum trichloride dust is a severe irritant to all tissues and reacts violently with water.

A mixture of naphthalene (5.25 g, 41 mmol), ferrocene (1; 7.63 g, 41 mmol), AlCl3 (10.9 g, 82 mmol), and Al powder (1.1 g, 0.041 mol) was refluxed in methylcyclohexane (120 mL) under N2 for 16 h. The mixture was cooled and ice (50 g) was added. The organic layer was separated and washed with H2O (3 × 100 mL). The combined aqueous fractions were washed with cyclohexane (2 × 30 mL) and filtered into sat. aq NH4PF6. Crystallization (acetone/Et2O) of the precipitate gave the product as orange flakes; yield: 5.4 g (33%); mp 166–168 °C (dec).

1.7.1.2 Method 2: Iron-Catalyzed Cycloaromatization

In organic synthesis, steps that form C—C bonds have special significance, so creating the arene ligand in the same step that attaches the metal is an attractive procedure. The required enediyne starting materials are readily available by Sonogashira coupling {see Science of Synthesis, Vol. 43 [Polyynes, Arynes, Enynes, and Alkynes (Section 43.4.1.1.1)]}. In this way, tris(acetonitrile)(η6-pentamethylcyclopentadienyl)iron [Fe(Cp*)(NCMe)3] reacts at room temperature with dodeca-6-ene-4,8-diyne to give the corresponding 1,2-dipropylarene complex in 76% yield.[96] The reaction uses dry acetone as the solvent and γ-terpinene as a hydrogen donor.

1.7.1.3 Method 3: Modification of η6-Complexes

Because η6-complexes of cyclopentadienyliron are cationic, they are powerful electrophiles and reaction with nucleophiles provides a major method to modify the η6-ligand, and so effect the synthesis of new structures of this type. The initial product is an η5-complex (see ▶ Section 1.7.2.9), but aromatization can re-form the η6-bonding. In particular, when leaving groups are present on the η6-ligand, nucleophile addition followed by loss of the leaving group re-forms the η6-structure in a one-pot procedure. In contrast, deprotonation next to the cationic η6-complexes affords neutral structures that react with electrophiles to form η6-products. Thus, cationic η6-ligated starting materials can be used in reaction sequences that employ both nucleophiles and electrophiles to modify the structure of the ligand. Similarly, conventional reactions of the metal-bound ligand can provide access to new structures of this class.

1.7.1.3.1 Variation 1: Replacement of Chloride in Chlorobenzene Complexes by Nucleophiles

▶ Scheme 5 Preparation of Substituted Arene–Cyclopentadienyliron Complexes by Replacement of Chloro or Nitro Groups by Nucleophiles[82–84,106]

R

1

R

2

X

Nu

Conditions

Yield (%)

Ref

Me

H

Cl

CH(CO

2

Et)

2

CH

2

(CO

2

Et)

2

, K

2

CO

3

, THF, DMSO, reflux, 5 h

HCl, NH

4

PF

6

67

[

83

]

H

Cl

Cl

CHAc

2

CH

2

Ac

2

, KF, Celite, THF, DMSO

76

[

82

]

Cl

H

Cl

NH(CH

2

)

2

NH

2

H

2

N(CH

2

)

2

NH

2

, K

2

CO

3

, THF, rt, 14 h

89

[

106

]

Me

H

Cl

CH(CO

2

Et)CN

CH

2

(CO

2

Et) CN, K

2

CO

3

, DMF, rt, 10 h

HCl, NH

4

PF

6

91

[

84

]

H

Me

Cl

CH(CO

2

Et)CN

CH

2

(CO

2

Et) CN, K

2

CO

3

, DMF, rt, 10 h

HCl, NH

4

PF

6

82

[

84

]

H

H

NO

2

CH(CO

2

Bn)

2

CH

2

(CO

2

Bn)

2

, KF, Celite, THF, DMSO, rt, 5 h

HCl, NH

4

PF

6

72

[

82

]

1.7.1.3.2 Variation 2: Use of Palladium-Catalyzed Coupling in the Presence of Cationic Iron–Cyclopentadienyl Complexes

The utility of chlorobenzene–cyclopentadienyliron complexes is extended by application of palladium-catalyzed cross coupling to effect replacement of chloride by aryl, alkenyl, and alkynyl substituents. Coupling to arylstannanes proceeds under normal conditions with tetrakis(triphenylphosphine) palladium(0), despite the fact that the carbon center for oxidative addition is bound to iron within the π-complex; however, with the cyclopentadienyliron complex it is possible to isolate an organopalladium intermediate.[111] Palladium-mediated carbonylation is also possible in the presence of the cyclopentadienyliron cation group.[112]

1.7.1.3.3 Variation 3: Use of Nucleophilic Complexes Obtained by Deprotonation of Arene–Cyclopentadienyliron Complexes

The benzylic position of cationic (alkylbenzene)(cyclopentadienyl)iron complexes is easily deprotonated to afford neutral intermediates that are effective as nucleophiles. The structures are elaborated by reaction with alkyl halides. Reactions with multiply substituted arenes are possible, or multiple alkylation of (η5-cyclopentadienyl)(η6-toluene)iron hexafluorophosphate (7) can be performed. Thus, (η5-cyclopentadienyl)(η6-hexamethylbenzene)iron hexafluorophosphate is converted into the hexabutyl analogue by reaction with potassium hydroxide and 1-bromopropane in 1,2-dimethoxyethane.[113] Allyl groups are introduced in a similar way,[113] and in a stepwise reaction sequence, the hexabutenyl product can be further elaborated to afford branched structures.[114]

Reaction of (η5-cyclopentadienyl)(η6-toluene)iron hexafluorophosphate (7) with potassium tert-butoxide or hydroxide and benzyl bromide affords the tribenzylated product (▶ Scheme 6).[115] A p-xylene ligand can be hexaallylated,[116] and from the corresponding mesitylene complex a nonaallylated product is possible.[117] The nonaallylation method is improved by reaction at room temperature in 1,2-dimethoxyethane, giving η6-arene complex 8 in 95% yield.[118] Substituents on the cyclopentadienyl ring can participate in redox steps in deprotonation reactions of the hexamethylbenzene ligand. For example, [Fe(η5-C5H4CH2NHPr)(η6-C6Me6)]+ is converted into [Fe(η5-C5H4CH=NPr)(η6-C6Me5=CH2)], which then reacts further with carbon dioxide and acid to form the cationic species [Fe(η5-C5H4CHO)(η6-C6Me5CH2CO2H)]+.[119]

▶ Scheme 6 Introduction of Electrophiles α to the Aromatic Ring of Iron–Cyclopentadienyl Complexes[115,118]

1.7.1.3.4 Variation 4: Ligand Modification by Ring-Closing Metathesis

Triallylation of the toluene complex 7 (▶ Section 1.7.1.3.3) affords a substrate for alkene metathesis. Two of the three CH=CH2 groups can be joined to form a cyclopentene in the modified ligand. The reaction is performed in 65% yield using the first-generation Grubbs’ catalyst [benzylidene(dichloro)(tricyclohexylphosphine)ruthenium(IV); Ru(=CHPh)Cl2(PCy3)2] {see Science of Synthesis, Vol. 47a [Alkenes (Section 47.1.1.6)]} in dichloromethane for 4 hours at room temperature.[120] The remaining alkene groups can undergo intermolecular metathesis in low yield by heating at reflux in 1,1,2,2-tetrachloroethane for 3 days. The difference in reaction conditions shows that the initial intramolecular step is much easier, and this accounts for the selectivity of the ring-closing metathesis (RCM) procedure.

1.7.1.3.5 Variation 5: Nucleophile Addition to a Carbonyl Ligand

Although tricarbonyliron complexes of dienes (see ▶ Section 1.7.3) are common, the isoelectronic η6-arene complexes of dicarbonyliron are virtually unknown. The only known example is prepared by an unusual series of reactions. First, an aryllithium reagent is added to a carbonyl ligand in tricarbonyl(η2, η2-cycloocta-1,5-diene)iron(0), to form an acyl intermediate that reacts with Meerwein's reagent (triethyloxonium tetrafluoroborate) with addition of the resulting dicarbonyliron–carbene moiety (see ▶ Section 1.7.4.6.1) to the cyclooctadiene ligand and transfer of the dicarbonyliron group to the arene.[121] Also rare are η6-complexes of tricarbonyliron, but these are isoelectronic with diene–tricarbonyliron complexes if the six-membered ring contains two boron atoms; for the synthesis of these, Grevels’ reagent (see ▶ Section 1.7.3.1.1) is used for the transfer of tricarbonyliron to the ligand.[122]

1.7.1.3.6 Variation 6: Modification of Functional Groups in the Presence of Cationic Iron–Cyclopentadienyl Complexes

Hydrogenation of the metal-free ring of η6-naphthalene complexes is promoted by the disruption of aromaticity that occurs on complexation to the cyclopentadienyliron cation. Palladium on charcoal can be used at ambient temperature and pressure to afford Tetralin complexes.[123]