Science of Synthesis Knowledge Updates 2018 Vol. 1 E-Book

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

Seitenzahl: 983

Veröffentlichungsjahr: 2017

Beschreibung

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. Several 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.

The Editorial Board

July 2010

E. M. Carreira (Zurich, Switzerland)

C. P. Decicco (Princeton, USA)

A. Fuerstner (Muelheim, Germany)

G. Koch (Basel, Switzerland)

G. A. Molander (Philadelphia, USA)

E. Schaumann (Clausthal-Zellerfeld, Germany)

M. Shibasaki (Tokyo, Japan)

E. J. Thomas (Manchester, UK)

B. M. Trost (Stanford, USA)

Abstracts

3.5.13 Silver-Promoted Coupling Reactions

J.-M. Weibel, A. Blanc, and P. Pale

Silver salts or complexes promote a variety of useful C—C bond-forming transformations in organic synthesis, usually under very mild conditions. In these reactions, silver can be engaged either as catalyst or cocatalyst, or as an organometallic reagent. Organosilver species act as mild nucleophiles toward alkyl halides or epoxides, but also toward carbonyl and imine derivatives and related heterocycles such as pyridines or quinolines. Silver can promote the homocoupling of a variety of organometallic reagents, of heterocycles, and of electron-deficient alkenes upon addition of the corresponding fluoride salts. Silver also promotes the cross coupling of alkyl or aryl halides, alkenes and alkynes, and even (het) arenes. Furthermore, silver salts often improve the efficiency of palladium-catalyzed cross-coupling reactions, or coupling reactions involving C—H activation or decarboxylation.

Keywords: silver • C—C bond formation • homocoupling • cross coupling • catalysis

24.4.3.5 1-(Organosulfanyl)-, 1-(Organoselanyl)-, and 1-(Organotellanyl)alk-1-ynes

A. Ulfkjær and M. Pittelkow

This chapter is an update to the earlier Science of Synthesis review (Section 24.4.3) describing the synthesis of 1-(organochalcogeno) alk-1-ynes, where the chalcogen is sulfur, selenium, or tellurium. It covers the literature from the period 2005–2016. Many of the approaches to these molecules involve reaction of an acetylide with a suitable chalcogen source, but other methods include the formation of the C≡C bond by elimination, the reaction of a chalcogenide species with alkynes bearing a leaving group at the alkyne terminus, and various types of coupling reactions. Also covered in this update are the recent applications of the title compounds. The wide range of reactions reported shows the importance of these molecules as building blocks and key intermediates in organic synthesis.

Keywords: sulfides • selenides • tellurides • chalcogens • thioethers • alkynes • acetylenes • acetylides • cross coupling • substitution • alkylation • cycloaddition

31.5.1.1.18 Synthesis of Phenols and Phenolates by Substitution

C. González-Bello

This chapter is an update to the earlier Science of Synthesis review (Section 31.5.1.1) describing the synthesis of monohydric phenols by substitution approaches. It focuses on the literature published in the period 2007–2016, with a particular emphasis on the recent C—H activation methods and hydroxylation by substitution of diverse functional groups, including boronic acids, silanes, and halides.

Keywords: phenols • phenolates • hydroxylation • photooxidation • C—H bond activation • metal-catalyzed hydroxylation • arylboronic acids • arylsilanes • alkoxy (aryl) silanes • aryl halides

31.5.1.2.7 Synthesis of Phenols and Phenolates by Elimination

C. González-Bello

This chapter is an update to the earlier Science of Synthesis review (Section 31.5.1.2), published in 2007, describing the synthesis of monohydric phenols by elimination approaches. It focuses on recent, palladium-catalyzed arylation/aromatization methods as well as the nickel-catalyzed hydrogenolysis of diaryl ethers.

Keywords: phenols • aromatization • arylation • tandem reaction • hydrogenolysis • cyclohexanones • cyclohexenones • diaryl ethers • palladium • nickel

31.5.1.3.6 Synthesis of Phenols and Phenolates by Rearrangement

C. González-Bello

This chapter is an update to the earlier Science of Synthesis review (Section 31.5.1.3) describing the synthesis of monohydric phenols by rearrangement. It focuses on the literature published in the period 2007–2016, with a particular emphasis on anionic and Lewis acid mediated Fries-type rearrangements.

Keywords: phenols • Fries-type rearrangement • arylation • tandem reaction • hydrogenolysis • dienones • allyl aryl ethers • Lewis acids • C-glycosylphenols • chlorosilanes • O-arylcarbamates

31.5.1.4.3 Synthesis of Phenols and Phenolates with Retention of the Functional Group

C. González-Bello

This chapter is an update to the earlier Science of Synthesis review (Section 31.5.1.4) describing the functionalization of monohydric phenols. It focuses on the literature published in the period 2007–2016, with a particular emphasis on metal-catalyzed alkylation methods as well as trifluoromethylsulfanylation approaches.

Keywords: phenols • halogenation • metal-catalyzed alkylation • trifluoromethylsulfanylation • hydrogenolysis • chlorophenols • C—H alkylation

31.40.3 Arylphosphinic Acids and Derivatives

D. Virieux, T. Ayad, J.-L. Pirat, and J.-N. Volle

This chapter is an update to Section 31.40 and describes published methods for the synthesis of arylphosphinic acids and derivatives reported from 2007 to early 2016. Reports on the syntheses of arylphosphinic acids and derivatives are limited to arylphosphinic acids and arylphosphinates [Ar1R1P(O)OH and Ar1R1P(O)OR2, respectively], for which R1 and R2 are a hydrogen atom or any kind of hydrocarbon substituent (e.g., alkyl, aryl, hetaryl).

Keywords: arylphosphinic acids • arylphosphinates • phosphines • phosphonites • phosphorus • phosphine oxides • arylation • transition-metal catalysis • esterification

32.2.6 Monofunctionalized Allenes

A. S. K. Hashmi

This chapter is an update to Science of Synthesis Section 32.2, covering the synthesis of allenes bearing one heteroatom substituent on the cumulated diene core. It covers the literature from 2008 to 2016. Many routes to these allenes start from alkynes, enynes, or propargylic systems and the syntheses proceed through substitution/rearrangement, but reactions involving the modification of an existing allene core are also included. In recent years, the synthesis of enantiomerically pure allenes has been of particular interest.

Keywords: allenes • haloallenes • allenyl ethers • allenyl sulfides • allenylamides • allenylamines • allenylphosphorus compounds • allenylsilanes • rearrangement • isomerization • alkynes • enynes • propargylic systems

3.12 General Aspects of Immobilized Biocatalysts and Their Applications in Flow

M. Bajić, P. Žnidaršič-Plazl, M. Kingston, and V. Hessel

This chapter is a comprehensive review of methods for the immobilization of biocatalysts, namely enzymes and whole cells, in microflow reactors. Immobilization on microchannel surfaces, in monoliths, hydrogels, membranes, or other internal structures within microreactors are described. The characteristics of packed-bed and magnetic-field-assisted microreactors and two-liquid-phase flow systems with immobilized biocatalysts and some applications are presented.

Keywords: enzymes • biocatalysis • immobilization • microfluidics • microreactors • miniaturized packed-bed reactors

Science of Synthesis Knowledge Updates 2018/1

Preface

Abstracts

Table of Contents

3.5.13 Silver-Promoted Coupling Reactions

J.-M. Weibel, A. Blanc, and P. Pale

24.4.3.5 1-(Organosulfanyl)-, 1-(Organoselanyl)-, and 1-(Organotellanyl) alk-1-ynes (Update 2018)

A. Ulfkjær and M. Pittelkow

31.5.1.1.18 Synthesis of Phenols and Phenolates by Substitution (Update 2018)

C. González-Bello

31.5.1.2.7 Synthesis of Phenols and Phenolates by Elimination (Update 2018)

C. González-Bello

31.5.1.3.6 Synthesis of Phenols and Phenolates by Rearrangement (Update 2018)

C. González-Bello

31.5.1.4.3 Synthesis of Phenols and Phenolates with Retention of the Functional Group (Update 2018)

C. González-Bello

31.40.3 Arylphosphinic Acids and Derivatives (Update 2018)

D. Virieux, T. Ayad, J.-L. Pirat, and J.-N. Volle

32.2.6 Monofunctionalized Allenes (Update 2018)

A. S. K. Hashmi

3.12 General Aspects of Immobilized Biocatalysts and Their Applications in Flow

M. Bajić, P. Žnidaršič-Plazl, M. Kingston, and V. Hessel

Author Index

Abbreviations

Table of Contents

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

3.5 Product Class 5: Organometallic Complexes of Silver

3.5.13 Silver-Promoted Coupling Reactions

J.-M. Weibel, A. Blanc, and P. Pale

3.5.13 Silver-Promoted Coupling Reactions

3.5.13.1 Organosilver Compounds as Nucleophiles

3.5.13.1.1 Nucleophilic Substitution

3.5.13.1.1.1 Method 1: Alkylations with Organosilver Compounds

3.5.13.1.1.1.1 Variation 1: Reactions of Silver Acetylides with Alkyl Halides

3.5.13.1.1.1.2 Variation 2: Reactions of Alkenylsilver Compounds with Alkyl Halides

3.5.13.1.1.2 Method 2: Epoxide Opening with Silver Acetylides

3.5.13.1.2 Nucleophilic Addition via Organosilver Compounds

3.5.13.1.2.1 Method 1: Alkynylation of Carbonyl Derivatives with Silver Acetylides

3.5.13.1.2.1.1 Variation 1: Reactions of Silver Acetylides with Acyl Halides

3.5.13.1.2.1.2 Variation 2: Reactions of Silver Acetylides with Aldehydes and Ketones

3.5.13.1.2.1.3 Variation 3: Reactions of In Situ Formed Silver Acetylides with Aldehydes and Ketones

3.5.13.1.2.1.4 Variation 4: Reactions of Silver Acetylides with Oxonium Intermediates

3.5.13.1.2.1.5 Variation 5: Reactions of Silver Acetylides with Carbon Dioxide

3.5.13.1.2.2 Method 2: Alkynylation of Imine Derivatives with Silver Acetylides

3.5.13.1.2.2.1 Variation 1: Reactions of Silver Acetylides with Imidoyl Chlorides

3.5.13.1.2.2.2 Variation 2: Reactions of Silver Acetylides with Iminium Salts

3.5.13.1.2.2.3 Variation 3: Addition Reaction between Alkynes and Imines Promoted by Silver

3.5.13.1.2.2.4 Variation 4: A3 Coupling Promoted by Silver

3.5.13.1.2.3 Method 3: Decarboxylative Addition of Arenecarboxylic Acids to Aldehydes and Imine Derivatives

3.5.13.2 Silver-Promoted Homocoupling Reactions

3.5.13.2.1 Method 1: Stoichiometric Homocoupling of Grignard Reagents

3.5.13.2.2 Method 2: Catalytic Homocoupling of Grignard Reagents

3.5.13.2.3 Method 3: Homocoupling of Alkenyllithium Reagents

3.5.13.2.4 Method 4: Homocoupling of Organosilicate Reagents

3.5.13.2.5 Method 5: Homocoupling of Boronic Acids

3.5.13.2.6 Method 6: Homocoupling of Alkylboranes

3.5.13.2.7 Method 7: Homocoupling of Fluoroalkenes

3.5.13.2.8 Method 8: Homocoupling of Alkynes

3.5.13.2.9 Method 9: Homocoupling of Thiophenes

3.5.13.2.10 Method 10: Decarboxylative Homocoupling of Benzoic Acids and Related Heteroaromatic Derivatives

3.5.13.3 Silver-Promoted Cross-Coupling Reactions

3.5.13.3.1 Silver-Promoted Cross Coupling of Alkyl Halides

3.5.13.3.1.1 Method 1: Silver-Catalyzed Benzylation and Allylation with Grignard Reagents and Related Organometallics

3.5.13.3.2 Silver-Promoted Cross Coupling with Alkenes

3.5.13.3.2.1 Method 1: Silver-Catalyzed Alkylation of Alkenes with Cyclopropanols

3.5.13.3.2.2 Method 2: Silver-Promoted Alkylation of Alkenes with Fluoroalkenes

3.5.13.3.2.3 Method 3: Silver-Promoted Trifluoromethylation of Alkenes

3.5.13.3.3 Silver-Promoted Cross Coupling of Alkynes

3.5.13.3.3.1 Method 1: Silver-Catalyzed Alkynylation of Aryl Halides

3.5.13.3.3.2 Method 2: Silver-Promoted Alkynylation of 1,3-Dicarbonyl Compounds

3.5.13.3.3.3 Method 3: Silver-Promoted Alkynylation of Benzamides and Related Heterocycles

3.5.13.3.4 Silver-Catalyzed Cross Coupling of Aryl Halides

3.5.13.3.4.1 Method 1: Silver-Catalyzed Coupling with Arylboronic Acids

3.5.13.3.4.2 Method 2: Silver-Catalyzed Coupling with Malononitrile

3.5.13.3.5 Silver-Promoted Cross Coupling of (Het) Arenes

3.5.13.3.5.1 Method 1: Silver-Promoted Trifluoromethylation of Benzene Derivatives

3.5.13.3.5.2 Method 2: Silver-Promoted ortho-Trifluoromethylation of Aryl Triazenes

3.5.13.3.5.3 Method 3: Silver-Promoted Fluoroalkylation of Aromatic Triazenes

3.5.13.3.5.4 Method 4: Silver-Promoted Trifluoromethylation of Arynes

3.5.13.3.5.5 Method 5: Silver-Catalyzed Alkenylation of Furans

3.5.13.3.5.6 Method 6: Silver-Catalyzed Cross Coupling of Five-Membered Heterocycles

3.5.13.4 Silver as Cocatalyst in Palladium-Promoted Cross-Coupling Reactions

3.5.13.4.1 Silver as Cocatalyst in Heck-Type Reactions

3.5.13.4.1.1 Method 1: Coupling of Vinylsilanes

3.5.13.4.1.2 Method 2: Coupling of Allylic Alcohols

3.5.13.4.1.3 Method 3: Coupling of Allenes

3.5.13.4.1.4 Method 4: Coupling of Alkenes

3.5.13.4.1.5 Method 5: Coupling of Dienes

3.5.13.4.1.6 Method 6: Intramolecular Coupling

3.5.13.4.2 Silver as Cocatalyst in Suzuki–Miyaura-Type Reactions

3.5.13.4.2.1 Method 1: Coupling of Arylboronic Acids

3.5.13.4.2.2 Method 2: Coupling of Alkenylboronic Acids

3.5.13.4.2.3 Method 3: Coupling of Alkylboronic Acids

3.5.13.4.2.4 Method 4: Coupling of Vinylboronates

3.5.13.4.2.5 Method 5: Coupling of Alkylboranes

3.5.13.4.3 Silver as Cocatalyst in Stille-Type Reactions

3.5.13.4.3.1 Method 1: Coupling of Stannylpyridines with Aryl Halides

3.5.13.4.3.2 Method 2: Coupling of Naphthylstannanes with Aryl Iodides

3.5.13.4.4 Silver as Cocatalyst in Hiyama-Type Reactions

3.5.13.4.4.1 Method 1: Coupling of Silanols with Aryl Halides

3.5.13.4.4.2 Method 2: Coupling of 2-Silylpyridines with Aryl Iodides

3.5.13.4.5 Silver as Cocatalyst in Sonogashira-Type Reactions

3.5.13.4.5.1 Method 1: Coupling of Terminal Alkynes

3.5.13.4.5.1.1 Variation 1: Silver as Cocatalyst in the Coupling of Terminal Alkynes with Aryl or Alkenyl Halides or Trifluoromethanesulfonates

3.5.13.4.5.1.2 Variation 2: Silver as Cocatalyst in the Coupling of Terminal Alkynes with Aryliodonium Salts

3.5.13.4.5.1.3 Variation 3: Silver as Cocatalyst in the Coupling of Terminal Alkynes with Arylboronic Acids or Boronates

3.5.13.4.5.1.4 Variation 4: Silver as Cocatalyst in the Coupling of Terminal Alkynes with Arylsiloxanes

3.5.13.4.5.2 Method 2: Coupling of Silylalkynes

3.5.13.5 Silver as Cocatalyst in Palladium-Promoted Coupling Reactions through C—H Activation

3.5.13.5.1 Silver as Cocatalyst in Electrophilic Aromatic Substitution

3.5.13.5.1.1 Method 1: Coupling of Aryl Halides with Arene Derivatives

3.5.13.5.1.2 Method 2: Coupling of Benzene Derivatives with Indoles

3.5.13.5.2 Silver as Activator or Cocatalyst in Directed Coupling Reactions

3.5.13.5.2.1 Method 1: Coupling with Nitrogen-Based Directing Groups

3.5.13.5.2.1.1 Variation 1: Silver as Activator in the Coupling of Aryl Iodides with Substituted Pyridines

3.5.13.5.2.1.2 Variation 2: Silver as Activator in the Coupling of Boronic Acids with Substituted Pyridines

3.5.13.5.2.1.3 Variation 3: Silver as Activator in the Coupling of Benzo[h]quinoline with Benzene Derivatives

3.5.13.5.2.2 Method 2: Coupling with Carboxylic Acid Derivatives as Directing Group

3.5.13.5.2.2.1 Variation 1: Silver as Activator in the Coupling of Aryl Iodides or Bromoalkynes with Anilides

3.5.13.5.2.2.2 Variation 2: Silver as Activator in the Coupling of Acrylates with Aryl Amides or Esters

3.5.13.5.2.3 Method 3: Coupling with a Carboxylic Acid as Directing Group

3.5.13.5.2.4 Method 4: Coupling with a Thiophene and Related Heterocycles as Directing Group

3.5.13.5.3 Silver as Activator in Cross-Coupling Reactions Involving Carbenoids

3.5.13.5.3.1 Method 1: Coupling of Aryl or Alkenyl Halides with Diazo Esters or Diazo Ketones

3.5.13.6 Silver as Cocatalyst or Activator in Decarboxylative Cross-Coupling Reactions

3.5.13.6.1 Silver as Activator in Decarboxylative Coupling of Arenecarboxylic Acids

3.5.13.6.1.1 Method 1: Decarboxylative Alkenylation of Arenecarboxylic Acids

3.5.13.6.1.2 Method 2: Decarboxylative Coupling of Arenecarboxylic Acids with Aryl Iodides or Diaryliodonium Salts

3.5.13.6.1.3 Method 3: Decarboxylative Coupling of Arenecarboxylic Acids with Organoboron Reagents

3.5.13.6.1.4 Method 4: Decarboxylative Coupling of Arenecarboxylic Acids with Nitroalkanes

3.5.13.6.2 Silver as Activator in Decarboxylative Couplings of Alkynoic Acids

3.5.13.6.2.1 Method 1: Decarboxylative Coupling of Alkynoic Acids with Organoboron Reagents

3.5.13.6.3 Silver as Activator in Decarboxylative Couplings of Arenecarboxylic Acids and C—H Activation

3.5.13.6.3.1 Method 1: Decarboxylative Coupling of Arenecarboxylic Acids with (Het) Arenes

3.5.13.6.3.2 Method 2: Decarboxylative Coupling of Arenecarboxylic Acids with Furans, Pyrroles, and Benzo[b]furans

Volume 24: Three Carbon—Heteroatom Bonds: Ketene Acetals and Yne—X Compounds

24.4 Product Class 4: 1-Heteroatom-Functionalized Alk-1-ynes

24.4.3.5 1-(Organosulfanyl)-, 1-(Organoselanyl)-, and 1-(Organotellanyl) alk-1-ynes

A. Ulfkjær and M. Pittelkow

24.4.3.5 1-(Organosulfanyl)-, 1-(Organoselanyl)-, and 1-(Organotellanyl) alk-1-ynes

24.4.3.5.1 (Organosulfanyl)-, (Organoselanyl)-, and (Organotellanyl) acetylenes

24.4.3.5.1.1 Synthesis of (Organosulfanyl)-, (Organoselanyl)-, and (Organotellanyl) acetylenes

24.4.3.5.1.1.1 Method 1: Synthesis from Alkali-Metal Acetylides

24.4.3.5.1.1.2 Method 2: Synthesis from Grignard Reagents

24.4.3.5.1.1.3 Method 3: Halogenation/Dehydrohalogenation Reactions

24.4.3.5.1.1.4 Method 4: Elimination Reactions

24.4.3.5.1.2 Applications of (Organosulfanyl)-, (Organoselanyl)-, and (Organotellanyl) acetylenes

24.4.3.5.1.2.1 Method 1: Nucleophilic Substitution Reactions with Alkali-Metal (Organochalcogeno) acetylides

24.4.3.5.1.2.1.1 Variation 1: Reaction of Acetylides with Chalcogen Electrophiles

24.4.3.5.1.2.1.2 Variation 2: Reaction of Acetylides with Carbonyl Electrophiles

24.4.3.5.1.2.1.3 Variation 3: Reaction of Acetylides with Haloalkane Electrophiles

24.4.3.5.1.2.2 Method 2: Addition Reactions of (Organochalcogeno) acetylenes

24.4.3.5.1.2.2.1 Variation 1: Addition of Organochalcogens To Form 1,1- and 1,2-Bis (organochalcogeno) alkenes

24.4.3.5.1.2.2.2 Variation 2: Addition of Other Reagents

24.4.3.5.1.2.3 Method 3: Cycloaddition Reactions of (Organochalcogeno) acetylenes

24.4.3.5.1.2.3.1 Variation 1: [2 + 2]-Cycloaddition Reactions

24.4.3.5.1.2.3.2 Variation 2: [2 + 3]-Cycloaddition Reactions

24.4.3.5.1.2.3.3 Variation 3: [2 +2+2]-Cycloaddition Reactions

24.4.3.5.1.2.4 Method 4: Additional Methods

24.4.3.5.2 Dialk-1-ynyl Sulfides, Selenides, and Tellurides

24.4.3.5.2.1 Synthesis of Dialk-1-ynyl Sulfides, Selenides, and Tellurides

24.4.3.5.2.1.1 Method 1: Synthesis from Alkali-Metal Acetylides

24.4.3.5.2.1.2 Method 2: Synthesis from Symmetrical Bis (aroylmethyl) Sulfides and Selenides

24.4.3.5.2.1.3 Method 3: Alkynylation of Sodium Hydrogen Sulfide

24.4.3.5.2.1.4 Method 4: Copper-Catalyzed Cross-Coupling Reactions

24.4.3.5.2.2 Applications of Dialk-1-ynyl Sulfides, Selenides, and Tellurides

24.4.3.5.2.2.1 Method 1: Stereoselective Reduction of Dialk-1-ynyl Sulfides

24.4.3.5.2.2.2 Method 2: Hydroalkoxylation and Hydrothiolation Reactions

24.4.3.5.2.2.3 Method 3: Reaction between Dialk-1-ynyl Sulfides and Metal Carbonyl Complexes

24.4.3.5.2.2.4 Method 4: Detelluration Reactions of Dialk-1-ynyl Tellurides

24.4.3.5.2.2.5 Method 5: Synthesis of Heterocyclic Compounds

24.4.3.5.2.2.5.1 Variation 1: 1,1-Carboboration and Frustrated Lewis Pair Addition Reactions

24.4.3.5.2.2.5.2 Variation 2: Alkylation of Sodium Sulfide

24.4.3.5.2.2.6 Method 6: Photorearrangement

24.4.3.5.3 1-(Alkylsulfanyl)- and 1-(Arylsulfanyl) alk-1-ynes and Their Selenium and Tellurium Analogues

24.4.3.5.3.1 Synthesis of 1-(Alkylsulfanyl)- and 1-(Arylsulfanyl) alk-1-ynes and Their Selenium and Tellurium Analogues

24.4.3.5.3.1.1 Method 1: Synthesis from Metal Acetylides, Molecular Chalcogens, and Haloalkanes

24.4.3.5.3.1.2 Method 2: Synthesis from Metal Acetylides and Electrophilic Chalcogen Species

24.4.3.5.3.1.3 Method 3: Synthesis from Metal (Organochalcogeno) acetylides

24.4.3.5.3.1.4 Method 4: Synthesis from Grignard Reagents

24.4.3.5.3.1.5 Method 5: Elimination Reactions

24.4.3.5.3.1.6 Method 6: Nucleophilic Substitution Reactions

24.4.3.5.3.1.7 Method 7: Cross-Coupling Reactions

24.4.3.5.3.1.7.1 Variation 1: Copper(I)-Catalyzed Cross-Coupling Reactions

24.4.3.5.3.1.7.2 Variation 2: Copper (II)-Catalyzed Cross-Coupling Reactions

24.4.3.5.3.1.7.3 Variation 3: Palladium (II)-Catalyzed Cross-Coupling Reactions

24.4.3.5.3.1.7.4 Variation 4: Indium (III)-Catalyzed Cross-Coupling Reactions

24.4.3.5.3.1.7.5 Variation 5: Cross-Coupling Reactions Catalyzed by Metallic Nanoparticles

24.4.3.5.3.1.7.6 Variation 6: Cross-Coupling Reactions Catalyzed by Other Metals

24.4.3.5.3.1.8 Method 8: Trifluoromethylchalcogenation Reactions

24.4.3.5.3.1.9 Method 9: Coordination Reactions with Organometallic Complexes

24.4.3.5.3.1.10 Method 10: Alkynylation Reactions Using Hypervalent Reagents

24.4.3.5.3.1.10.1 Variation 1: Reactions Using Hypervalent Iodine Reagents

24.4.3.5.3.1.10.2 Variation 2: Reactions Using Hypervalent Sulfur Reagents

24.4.3.5.3.1.10.3 Variation 3: Reactions Using Hypervalent Bromine Reagents

24.4.3.5.3.1.11 Method 11: Base-Catalyzed Isomerization of Terminal Alkynes

24.4.3.5.3.1.12 Method 12: Base-Catalyzed Ring-Opening Reactions of Thia- and Selenadiazoles

24.4.3.5.3.1.13 Method 13: Additional Methods

24.4.3.5.3.2 Applications of 1-(Alkylsulfanyl)- and 1-(Arylsulfanyl) alk-1-ynes and Their Selenium and Tellurium Analogues

24.4.3.5.3.2.1 Method 1: Substitution Reactions of (Organochalcogeno) acetylenes

24.4.3.5.3.2.2 Method 2: Addition Reactions of (Organochalcogeno) acetylenes

24.4.3.5.3.2.2.1 Variation 1: Addition of Organochalcogens To Form 1,1- and 1,2-Bis (organochalcogeno) alkenes

24.4.3.5.3.2.2.2 Variation 2: Addition of Organometallics

24.4.3.5.3.2.2.3 Variation 3: Addition of Other Reagents

24.4.3.5.3.2.3 Method 3: Cycloaddition Reactions of (Organochalcogeno) acetylenes

24.4.3.5.3.2.3.1 Variation 1: [2 + 2]-Cycloaddition Reactions

24.4.3.5.3.2.3.2 Variation 2: [2 + 3]-Cycloaddition Reactions

24.4.3.5.3.2.3.3 Variation 3: [2 + 4]-Cycloaddition Reactions

24.4.3.5.3.2.3.4 Variation 4: Other Cycloaddition Reactions

24.4.3.5.3.2.4 Method 4: Sigmatropic Rearrangements of (Organochalcogeno) acetylenes

24.4.3.5.3.2.5 Method 5: Cyclization Reactions of (Organochalcogeno) acetylenes

24.4.3.5.3.2.5.1 Variation 1: Electrophilic Cyclization Reactions

24.4.3.5.3.2.5.2 Variation 2: Acid-Catalyzed Cyclization Reactions

24.4.3.5.3.2.5.3 Variation 3: Base-Catalyzed Cyclization Reactions

24.4.3.5.3.2.5.4 Variation 4: Cyclization of 4-Oxa- and 4-Azahepta-1,6-diynes and Other Diynes

24.4.3.5.3.2.5.5 Variation 5: Cyclization of 3-Sulfanyl- and 3-Selanylpropargyl Alcohols

24.4.3.5.3.2.5.6 Variation 6: Cyclization of Ethynyl Dithiocarbamates

24.4.3.5.3.2.5.7 Variation 7: Metal-Catalyzed Cycloisomerization Reactions

24.4.3.5.3.2.6 Method 6: Transition-Metal-Coordinated Complexes of (Organochalcogeno) acetylenes

24.4.3.5.3.2.7 Method 7: Dechalcogenation Reactions of (Organochalcogeno) acetylenes

24.4.3.5.3.2.8 Method 8: Acid Hydrolysis of (Organochalcogeno) acetylenes

24.4.3.5.3.2.9 Method 9: Base-Catalyzed Isomerization of the Alkyne in (Organochalcogeno) acetylenes

24.4.3.5.3.2.10 Method 10: Oxidation Reactions of 1-(Alkylsulfanyl)- and 1-(Arylsulfanyl) alk-1-ynes

24.4.3.5.3.2.11 Method 11: Additional Methods

24.4.3.5.4 1-(Vinylsulfanyl)-, 1-(Vinylselanyl)-, and 1-(Vinyltellanyl) alk-1-ynes

24.4.3.5.4.1 Synthesis of 1-(Vinylsulfanyl)-, 1-(Vinylselanyl)-, and 1-(Vinyltellanyl) alk-1-ynes

24.4.3.5.4.1.1 Method 1: Horner–Wittig Reaction

24.4.3.5.4.1.2 Method 2: Nucleophilic Ring Opening of Epoxides Followed by Elimination

24.4.3.5.4.1.3 Method 3: Reaction of Metal Acetylides with Bunte Salts

24.4.3.5.4.1.4 Method 4: Hydroalkoxylation and Hydrothiolation Reactions

24.4.3.5.4.1.5 Method 5: Copper-Catalyzed Cross-Coupling Reactions

24.4.3.5.4.2 Applications of 1-(Vinylsulfanyl)-, 1-(Vinylselanyl)-, and 1-(Vinyltellanyl) alk-1-ynes

24.4.3.5.4.2.1 Method 1: Oxidation of 1-(Vinylsulfanyl) alk-1-ynes

24.4.3.5.4.2.2 Method 2: Reaction between 1-(Vinylsulfanyl) alk-1-ynes and Carbonyl Metals

31.5 Product Class 5: Phenols and Phenolates

31.5.1.1.18 Synthesis of Phenols and Phenolates by Substitution

C. González-Bello

31.5.1.1.18 Synthesis of Phenols and Phenolates by Substitution

31.5.1.1.18.1 Method 1: Substitution of Hydrogen

31.5.1.1.18.1.1 Variation 1: Direct Oxidation with Nitrous Oxide or Hydrogen Peroxide

31.5.1.1.18.1.2 Variation 2: Photocatalysis

31.5.1.1.18.1.3 Variation 3: Activation of C—H Bonds

31.5.1.1.18.2 Method 2: Substitution of Arylboronic Acids

31.5.1.1.18.3 Method 3: Substitution of Arylsilanes and Alkoxy (aryl) silanes

31.5.1.1.18.4 Method 4: Substitution of Aryl Halides

31.5.1.2.7 Synthesis of Phenols and Phenolates by Elimination

C. González-Bello

31.5.1.2.7 Synthesis of Phenols and Phenolates by Elimination

31.5.1.2.7.1 Method 1: Aromatization of Cyclohexanones and Cyclohexenones

31.5.1.2.7.2 Method 2: Hydrogenolysis of Diaryl Ethers

31.5.1.3.6 Synthesis of Phenols and Phenolates by Rearrangement

C. González-Bello

31.5.1.3.6 Synthesis of Phenols and Phenolates by Rearrangement

31.5.1.3.6.1 Method 1: Rearrangement of Allyl Aryl Ethers

31.5.1.3.6.2 Method 2: Rearrangement of Dienones

31.5.1.3.6.3 Method 3: Rearrangement of Phenolic Esters and Related Reactions

31.5.1.4.3 Synthesis of Phenols and Phenolates with Retention of the Functional Group

C. González-Bello

31.5.1.4.3 Synthesis of Phenols and Phenolates with Retention of the Functional Group

31.5.1.4.3.1 Method 1: Halogenation of Phenols

31.5.1.4.3.2 Method 2: Alkylation and Acylation of Phenols

31.5.1.4.3.3 Method 3: Trifluoromethylsulfanylation of Phenols

31.40 Product Class 40: Arylphosphinic Acids and Derivatives

31.40.3 Arylphosphinic Acids and Derivatives

D. Virieux, T. Ayad, J.-L. Pirat, and J.-N. Volle

31.40.3 Arylphosphinic Acids and Derivatives

31.40.3.1 Arylphosphinic Acids

31.40.3.1.1 Synthesis from Tricoordinate Phosphorus Derivatives

31.40.3.1.1.1 Method 1: Synthesis From Phosphines by Cleavage of a P—C Bond and Oxidation

31.40.3.1.2 Synthesis from Tetracoordinate Phosphorus Derivatives

31.40.3.1.2.1 Method 1: Arylation of Phosphinic Acid or Derivatives

31.40.3.1.2.1.1 Variation 1: Palladium-Catalyzed Arylation of Anilinium Phosphinate

31.40.3.1.2.1.2 Variation 2: Copper-Catalyzed Arylation of H-Phosphinic Acids

31.40.3.1.2.2 Method 2: Modification of Aryl Groups: ortho-Lithiation of Diarylphosphinic Acids

31.40.3.1.2.3 Method 3: Alkylation of H-Phosphinic Acids

31.40.3.1.2.3.1 Variation 1: Palladium-Catalyzed Reactions of Alcohols

31.40.3.1.2.3.2 Variation 2: Alkylation of Aryl-H-phosphinic Acids with Ketones

31.40.3.1.2.3.3 Variation 3: Addition to Alkenes or Alkynes

31.40.3.2 Arylphosphinic Esters

31.40.3.2.1 Synthesis from Tricoordinate Phosphorus Derivatives

31.40.3.2.1.1 Method 1: Synthesis from Phosphines by Cleavage of a P—C Bond

31.40.3.2.1.2 Method 2: Synthesis from Arylphosphonites

31.40.3.2.1.2.1 Variation 1: Copper-Catalyzed Arylation of Arylphosphonites

31.40.3.2.1.2.2 Variation 2: Lanthanum-Catalyzed Arylation of Arylphosphonites

31.40.3.2.1.2.3 Variation 3: Bismuth-Catalyzed Arylation of Arylphosphonites

31.40.3.2.1.2.4 Variation 4: Arylation Reactions of Phosphonites with Arynes

31.40.3.2.1.2.5 Variation 5: Bromotrimethylsilane-Catalyzed Arbuzov Rearrangement of Arylphosphonites

31.40.3.2.1.2.6 Variation 6: Intermolecular Abramov Reaction of Arylphosphonites

31.40.3.2.1.2.7 Variation 7: Intramolecular Abramov Reaction of Arylphosphonites

31.40.3.2.1.2.8 Variation 8: Reactions of Arylphosphonites with Imines

31.40.3.2.1.2.9 Variation 9: Reactions of Arylphosphonites with [(Acylamino) alkyl]phosphonium Salts

31.40.3.2.1.2.10 Variation 10: Reactions of Arylphosphonites with Dibromoalkenes

31.40.3.2.1.2.11 Variation 11: Four-Component Reaction of a Phosphonite, an Acrylate, an Aldehyde, and Water

31.40.3.2.1.3 Method 3: Hydrolysis of Phosphorochloridites

31.40.3.2.1.4 Method 4: α-Aminoalkylation of Aryl (dichloro) phosphines

31.40.3.2.2 Synthesis from Tetracoordinate Phosphorus Derivatives

31.40.3.2.2.1 Method 1: One-Pot Esterification/Palladium-Catalyzed Arylation of Anilinium Phosphinate

31.40.3.2.2.2 Method 2: Nucleophilic Arylation or Alkylation of Phosphonates

31.40.3.2.2.3 Method 3: Palladium-Catalyzed Arylation of H-Phosphinates

31.40.3.2.2.3.1 Variation 1: Reactions of Aryl Halides

31.40.3.2.2.3.2 Variation 2: Reactions of Aryl Sulfonate Esters

31.40.3.2.2.3.3 Variation 3: Reactions of Arylboronic Acids

31.40.3.2.2.3.4 Variation 4: Reactions of Aryl Hydrazines

31.40.3.2.2.3.5 Variation 5: Reactions of Triarylbismuths

31.40.3.2.2.4 Method 4: Nickel-Catalyzed Arylation of H-Phosphinates

31.40.3.2.2.4.1 Variation 1: Reactions of Aryl Halides and Aryl Sulfonate Esters

31.40.3.2.2.4.2 Variation 2: Reactions of Arylboronic Acids

31.40.3.2.2.4.3 Variation 3: Reactions of Aryl Pivalates

31.40.3.2.2.5 Method 5: Copper-Catalyzed Arylation of H-Phosphinates

31.40.3.2.2.5.1 Variation 1: Reactions of Aryl Halides

31.40.3.2.2.5.2 Variation 2: Reactions of Diaryliodonium Salts

31.40.3.2.2.5.3 Variation 3: C—H Activation of Indoles

31.40.3.2.2.5.4 Variation 4: Reactions of Tosylhydrazones

31.40.3.2.2.6 Method 6: Other Arylation Methods of H-Phosphinates

31.40.3.2.2.6.1 Variation 1: Gold-Catalyzed Reactions of Aryldiazonium Species

31.40.3.2.2.6.2 Variation 2: Reactions of Arynes

31.40.3.2.2.6.3 Variation 3: C—H Activation of Benzothiazoles

31.40.3.2.2.7 Method 7: Modification of Aryl Groups

31.40.3.2.2.7.1 Variation 1: Synthesis of Substituted Phenanthridines by Radical Phosphorylation of 2-Isocyanobiphenyls

31.40.3.2.2.7.2 Variation 2: Rhodium- and Ruthenium-Catalyzed Reactions

31.40.3.2.2.7.3 Variation 3: Intramolecular C—H Activation of Arenes

31.40.3.2.2.7.4 Variation 4: Phospho-Fries Rearrangement of Phosphonates

31.40.3.2.2.7.5 Variation 5: ortho-Lithiation of Phosphinimidic Amides

31.40.3.2.2.8 Method 8: Alkenylation Reactions of Arylphosphinates

31.40.3.2.2.8.1 Variation 1: Palladium-Catalyzed Reactions of Terminal Alkynes

31.40.3.2.2.8.2 Variation 2: Copper-Catalyzed Reactions of Terminal Alkynes

31.40.3.2.2.8.3 Variation 3: Copper-Catalyzed Coupling of Alkynoic Acids

31.40.3.2.2.8.4 Variation 4: Tributylphosphine-Catalyzed Hydrophosphinylation of Ethyl 3-Phenylpropynoate

31.40.3.2.2.8.5 Variation 5: Copper-Catalyzed Decarboxylative C—P Coupling Reaction of Cinnamic Acid Derivatives with Ethyl Phenyl-H-phosphinate

31.40.3.2.2.8.6 Variation 6: Copper-Catalyzed Oxidative Cross-Coupling Reaction of 1,1-Diphenylethene with Phenyl-H-phosphinates

31.40.3.2.2.8.7 Variation 7: Nickel-Catalyzed Decarboxylative C—P Coupling Reaction of Cinnamic Acid Derivatives with Ethyl Phenyl-H-phosphinate

31.40.3.2.2.8.8 Variation 8: Nickel(II)/Magnesium-Catalyzed Cross-Coupling Reaction of (2,2-Dibromovinyl) benzene with Aryl-H-phosphinates

31.40.3.2.2.8.9 Variation 9: Formation of Allenyl (aryl) phosphinates

31.40.3.2.2.8.10 Variation 10: Formation of 1,2-Oxaphospholenes by the Copper-Catalyzed Reaction of Oxazirconacyclopentenes with Dichloro (phenyl) phosphine

31.40.3.2.2.9 Method 9: Alkynylation Reactions of Arylphosphinates

31.40.3.2.2.9.1 Variation 1: Metal-Catalyzed Reactions of Terminal Alkynes

31.40.3.2.2.9.2 Variation 2: Reactions of Hypervalent Iodoalkynes

31.40.3.2.2.10 Method 10: Alkylation of H-Phosphinic Acids and Derivatives

31.40.3.2.2.10.1 Variation 1: Copper-Catalyzed Radical Hydrophosphinylation of Unactivated Alkenes

31.40.3.2.2.10.2 Variation 2: Nickel-Catalyzed Hydrophosphinylation of Unactivated Alkenes and Subsequent Palladium-Catalyzed Arylation of Alkylphosphinates

31.40.3.2.2.10.3 Variation 3: Silver-Catalyzed Radical Hydrophosphinylation of Unactivated Alkenes

31.40.3.2.2.10.4 Variation 4: Manganese-Mediated Chlorophosphinylation of Oct-1-ene with Ethyl Phenyl-H-phosphinate

31.40.3.2.2.10.5 Variation 5: Manganese(III)-Mediated Hydrophosphinylation/Lactonization Reaction of 4-Phenylpent-4-enoic Acid with Ethyl Phenyl-H-phosphinate

31.40.3.2.2.10.6 Variation 6: Silver-Promoted Radical Hydrophosphinylation of α,α-Diaryl Allylic Alcohols

31.40.3.2.2.10.7 Variation 7: Trimethylphosphine-Promoted Addition of Aryl-H- phosphinates to Vinylphosphoryl Compounds

31.40.3.2.2.10.8 Variation 8: Hydrophosphinylation/Cycloetherification Reaction of 4-Phenylpent-4-en-1-ol with Ethyl Phenyl-H-phosphinate

31.40.3.2.2.10.9 Variation 9: Air-Induced Anti-Markovnikov Addition of H-Phosphinates to Unactivated Alkenes

31.40.3.2.2.10.10 Variation 10: Tandem Esterification/Hydroxyalkylation of H-Phosphinic Acids

31.40.3.2.2.10.11 Variation 11: Formation of Aryl (benzoyl) phosphinates

31.40.3.2.2.10.12 Variation 12: Formation of β-Keto Arylphosphinates

31.40.3.2.2.10.13 Variation 13: Formation of Arylmethyl (aryl) phosphinates

31.40.3.2.2.11 Method 11: Formation of the P—O—C Unit

31.40.3.2.2.11.1 Variation 1: Benzoxaphosphole 1-Oxide Synthesis by Palladium-Catalyzed Intramolecular C—H Activation/C—O Cyclization

31.40.3.2.2.11.2 Variation 2: Direct Reaction of Arylphosphinic Acids with Alcohols under Microwave Activation

31.40.3.2.2.11.3 Variation 3: O-Alkylation of Diphenyl Phosphinic Acid by Alkyl Halides

31.40.3.2.2.11.4 Variation 4: Reaction of Arylphosphinic Acids with Alcohols by Formation of Mixed Anhydride Intermediates

31.40.3.2.2.11.5 Variation 5: Copper-Catalyzed Reaction of Secondary Arylphosphine Oxides with Alcohols

31.40.3.2.2.11.6 Variation 6: Rhodium-Catalyzed Reaction of Diphenylphosphine Oxide with Nitrobenzene Derivatives

31.40.3.2.2.11.7 Variation 7: Atherton–Todd Reaction of Alcohols with Diphenylphosphine Oxide

31.40.3.2.2.11.8 Variation 8: α-Phosphoryloxylation of Ketones with Diphenylphosphine Oxide

31.40.3.2.2.11.9 Variation 9: Phosphoryloxylation of Benzylic C—H Bonds with Diphenylphosphine Oxide

31.40.3.2.2.11.10 Variation 10: Reaction of Diphenylphosphine Oxide with Tetrahydrofuran and a Hypervalent Iodine Reagent

31.40.3.2.2.11.11 Variation 11: Phospha-Baeyer–Villiger Oxidation of a 7-Phosphanorbornene

31.40.3.2.2.11.12 Variation 12: Copper-Catalyzed Aerobic Oxidative Esterification of Phosphinic Acids

31.40.3.2.2.12 Method 12: Synthesis of Aryl-H-phosphinates from (Hydroxymethyl) phosphinates

32.2 Product Class 2: Monofunctionalized Allenes and Higher Cumulenes

32.2.6 Monofunctionalized Allenes

A. S. K. Hashmi

32.2.6 Monofunctionalized Allenes

32.2.6.1 Haloallenes

32.2.6.1.1 Method 1: Fluoroallenes by Isomerization of Propargylic Fluorides

32.2.6.1.2 Method 2: Haloallenes by Saucy–Marbet Rearrangement of 1-Haloalkynes

32.2.6.1.3 Method 3: Bromoallenes by Bromination/Isomerization of Propargylic Alcohols with a Copper(I)/Copper (0) Catalyst

32.2.6.1.4 Method 4: Chloro-, Bromo-, and Iodoallenes from Alkynes and Benzil

32.2.6.1.5 Method 5: Iodoallenes from Alkynes and Epoxides

32.2.6.1.6 Method 6: Bromoallenes by Mercury-Mediated Intramolecular Hydroalkoxylation of Bromo-1,3-enynes

32.2.6.1.7 Method 7: Bromo- and Iodoallenes by Ring-Opening of Alkynyl Epoxides

32.2.6.1.8 Method 8: Bromoallenes from Propargylic Alcohols Using Niobium (V) Bromide

32.2.6.1.9 Method 9: Bromoallenes from Propargyl Alcohols Using Triphenylphosphine/Carbon Tetrabromide

32.2.6.1.10 Method 10: Bromoallenes from 1,3-Enynes by Intramolecular Bromoetherification

32.2.6.1.11 Method 11: Iodoallenes by Electrophilic Addition to Alkynyl-Substituted Silyl Ketene Acetals

32.2.6.2 (Organochalcogeno) allenes

32.2.6.2.1 Method 1: Oxygen-Substituted Allenes by Isomerization of Propargyl Ethers Using Potassium tert-Butoxide

32.2.6.2.2 Method 2: Oxygen-Substituted Allenes by Isomerization of Propargyl Ethers Using tert-Butyllithium

32.2.6.2.3 Method 3: Oxygen-Substituted Allenes by Deprotonation/Alkylation of Allenyl Ethers

32.2.6.2.4 Method 4: In Situ Formation of Allenyl Thioethers/Selenoethers by Isomerization of Propargyl Thioethers/Selenoethers

32.2.6.2.5 Method 5: Sulfur-Substituted Allenes by Sigmatropic Rearrangement

32.2.6.2.6 Method 6: Sulfur- and Selenium-Substituted Allenes by Propargylic Substitution

32.2.6.3 Nitrogen-Functionalized Allenes

32.2.6.3.1 Method 1: Allenylamides by Copper-Catalyzed Coupling of Haloallenes with Amides

32.2.6.3.2 Method 2: Triazolylallenes by Iron-Catalyzed Dehydrative Coupling of Propargylic Alcohols and Triazoles

32.2.6.3.3 Method 3: Aminoallenes from Other Aminoallenes by Metalation/α-Alkylation Reactions

32.2.6.4 Phosphorus-Functionalized Allenes

32.2.6.4.1 Method 1: Bis-allenes with Phosphorus Substituents by Zirconium-Mediated Coupling

32.2.6.4.2 Method 2: Sigmatropic Rearrangement to Allenylphosphine Oxides

32.2.6.4.3 Method 3: Allenylphosphonates from Allylphosphonates by Elimination and Metalation Followed by Reaction with an Aldehyde

32.2.6.4.4 Method 4: Allenylphosphonates by Palladium-Catalyzed Coupling of Activated Propargylic Substrates and H-Phosphonate Esters or Secondary Phosphine Oxides

32.2.6.5 Silicon- and Tin-Functionalized Allenes

32.2.6.5.1 Method 1: Bis-allenes with Silicon Substituents by Zirconium-Mediated Coupling

32.2.6.5.2 Method 2: Metalation of Propargyl Ethers and Quenching with Silicon or Tin Chlorides

Special Topic

3.12 General Aspects of Immobilized Biocatalysts and Their Applications in Flow

M. Bajić, P. Žnidaršič-Plazl, M. Kingston, and V. Hessel

3.12 General Aspects of Immobilized Biocatalysts and Their Applications in Flow

3.12.1 Biocatalyst Immobilization on Microchannel Surfaces

3.12.1.1 Biocatalyst Immobilization via Microreactor Surface Modification and Cross-Linking

3.12.1.2 Biocatalyst Immobilization via Molecular Recognition

3.12.1.3 Biocatalyst Immobilization on Increased Inner Microreactor Surfaces Using Nanostructured Materials

3.12.1.4 Biocatalyst Immobilization via Engineering of Enzyme Surface

3.12.1.4.1 Immobilization of Engineered Enzymes Containing a Histidine Tag

3.12.1.4.2 Immobilization of Engineered Enzymes Containing Zbasic2 Tag

3.12.1.5 Biofilms within Microfluidic Structures

3.12.2 Biocatalyst Immobilization within Monolithic Structures

3.12.2.1 Immobilization on Monoliths Prepared by Sol-Gel Techniques

3.12.2.2 Anchoring Enzymes to Surface-Modified Monoliths

3.12.3 Membrane-Based Microreactors

3.12.3.1 Enzymatic Membrane Reactors

3.12.3.1.1 Miniaturized Reactors with Suspended Enzymes

3.12.3.1.2 Miniaturized Reactors with Enzymes Immobilized on Membranes

3.12.3.2 Membrane Microreactor Applications

3.12.3.2.1 Membrane Microreactors for Peptide Analysis

3.12.3.2.2 Biodiesel Production Using Membrane Microreactors

3.12.4 Hydrogel-Based Microreactors

3.12.4.1 Hydrogel Microreactors with Immobilized Enzymes

3.12.4.2 Whole-Cell Immobilized Hydrogel Microreactors

3.12.4.2.1 Whole-Cell Immobilization by Photopolymerization

3.12.4.3 Applications of Hydrogel Microreactors

3.12.4.3.1 Protein Profiling Using Digital Hydrogel Reactors

3.12.4.3.2 Hydrogel Microreactors as Biosensors

3.12.4.3.3 Hydrogel Microreactor for Drug Delivery

3.12.5 Packed-Bed Meso- and Microbioreactors

3.12.5.1 Mass Transfer in Packed-Bed Reactors

3.12.5.2 The Main Properties of Biocatalyst Carriers

3.12.5.3 Typical Designs of Packed-Bed Meso- and Microbioreactors

3.12.6 Magnetic-Field-Assisted Microbioreactors

3.12.6.1 Impact of Magnetic Field on Reactor Performance

3.12.6.2 Applications of Magnetically Assisted Microreactors

3.12.6.2.1 Magnetic Microreactors for Thermal Regulation

3.12.6.2.2 Microchip Reactors with Enzymes Immobilized by Magnetic Nanoparticles

3.12.7 Two-Liquid-Phase Flow with Immobilized Biocatalysts within Microfluidic Structures

3.12.8 Conclusions

Author Index

Abbreviations

3.5.13 Silver-Promoted Coupling Reactions

J.-M. Weibel, A. Blanc, and P. Pale

General Introduction

After the emergence of organometallic chemistry in the middle of the 19th century with Frankland's report of the first organozincs,[1] the rich organomagnesium chemistry promoted by Grignard at the turn of the 20th century stimulated the exploration of related reactivity with zinc, cadmium, mercury, copper, silver, and gold. Although remaining at that time mostly based on stoichiometric amounts of their salts and organometallics, these metals nevertheless offered interesting methods for the formation of C—C bonds, one of the key transformations in organic synthesis. Since these early developments, techniques and methods have evolved to provide numerous routes to establish C—C bonds based on the properties of the salts and/or organometallics of these metals. Among them, silver salts and the corresponding organometallics have been widely applied. However, for a long time, silver salts were mostly used as halide scavengers in many reactions, from nucleophilic substitutions to eliminations and rearrangements, through organometallic activation. Nevertheless, the organometallic chemistry of silver has steadily evolved, mostly focusing on the access to these organometallics and on some applications. In parallel, the peculiar properties of silver and its derivatives have allowed various, often new, transformations to be performed under mild conditions, establishing silver and its derivatives as unique tools in organic synthesis.[2–6] The organic chemistry of silver has bloomed since the beginning of the 21st century (▶ Figure 1).[7]

Figure 1 Number of Published Papers Involving Silver and Organic Synthesis between 1879 and 2014 (from a SciFinder Analysis Performed in 2015)

Although less intense than in the case of gold, silver benefits from relativistic effects (▶ Figure 2).[8] The latter imposes s- and p-orbital contractions, leading to their stabilization and thus to a lower HOMO for Ag0 but to a lower LUMO for Ag+. Indirectly, these effects generate d- and f-orbital dilatation and lead to their destabilization. The latter, as well as an increased spin-orbit coupling, gives a higher HOMO to Ag+. Furthermore, increased backdonation can take place, giving some stabilization to alkenyl, aryl, alkynyl, and even carbene organosilver compounds and rendering them more nucleophilic. Silver(I) salts are thus reactive as Lewis acids, in particular with unsaturated systems having low-lying empty orbitals, especially alkynes. The chemistry of silver is thus driven by these properties, through the formation of σ-, π-, carbene, and carbonyl complexes (▶ Table 1).[9]

Figure 2 Influence of Relativistic Effects on the Frontier Orbitals of the Coinage Metals[8]

Table 1 Comparison of the σ- and π-Coordination Ability of the Coinage Metals [Calculated ΔHf (kcal•mol–1)][9]

BCl

3

CuCl

AgCl

AuCl

AuCl

3

PhC≡CH

0.9

33.1

22.6

34.7

32.5

PhCH=CH

2

0.4

33.6

24.4

37.5

36.8

PhCHO

18.9

37.4

26.4

33.1

35.9

The purpose of this chapter is to cover synthetic applications of silver for the formation of C—C bonds through coupling reactions. These encompass a variety of reactions promoted by a metal catalyst, in which new C—C bonds are created. For silver and its salts and complexes, the corresponding organic chemistry can be divided according to the properties mentioned above, i.e. into the nucleophilic behavior of organosilver compounds, the role of silver as σ-Lewis acid, and the involvement of silver in homocoupling and cross-coupling reactions. In the present contribution, we will only focus on the nucleophilic behavior, homocoupling, and cross-coupling reactions of organosilver compounds.

3.5.13.1 Organosilver Compounds as Nucleophiles

3.5.13.1.1 Nucleophilic Substitution

3.5.13.1.1.1 Method 1: Alkylations with Organosilver Compounds

As is the case with most organometallics, organosilver compounds are often aggregates. This structural feature limits their reactivity to a certain extent, and especially their nucleophilicity. Nevertheless, a few examples are known, mostly involving silver acetylides.

3.5.13.1.1.1.1 Variation 1: Reactions of Silver Acetylides with Alkyl Halides

Although polymeric substances,[10] silver acetylides can react as nucleophiles with various alkyl halides, provided that the reaction is performed in polar solvents, probably to dissociate the organometallic polymer. Such reactions provide the corresponding disubstituted acetylenes in good to high yields. The silver acetylide 1 derived from methyl undec-10-ynoate reacts with neat iodomethane or iodoethane to give the corresponding alkylated acetylene derivatives (e.g., 2) (▶ Scheme 1).[11] Silver acetylides (e.g., 3) can even react with 1-adamantyl bromide or iodide and related bridged systems, such as bicyclo[2.2.2]octanes, in refluxing N-methylmorpholine or pyridine, to furnish 1-adamantylated acetylenes 4, probably through an SRN1 mechanism (▶ Scheme 2).[12,13]

Scheme 1 Alkylation of a Silver Acetylide[11]

Scheme 2 Alkylation of Silver Acetylides with 1-Iodoadamantane[13]

R

1

R

2

Yield (%)

Ref

H

H

68

[

13

]

H

(CH

2

)

4

Me

57

[

13

]

Cl

H

62

[

13

]

H

Br

20

[

13

]

Methyl Dodec-10-ynoate (2):[11]

CAUTION:

Iodomethane is a carcinogen. Proper precautions should be taken during its handling.

A mixture of (11-methoxy-11-oxoundec-1-ynyl) silver (1; 12.7 g, 42 mmol) and MeI (10 mL) was heated at 75 °C in a sealed tube overnight. The solid was filtered off and washed with Et2O. The solvent was removed from the filtrate by distillation, and the residue was distilled under reduced pressure from a Späth bulb in an air furnace at 85 °C; yield: 4 mL (45%).

1-(Arylethynyl) adamantanes 4; General Procedure:[13]

CAUTION:

Sodium azide can explode on heating and is highly toxic. Contact of metal azides with acids liberates the highly toxic and explosive hydrazoic acid.

A silver(I) arylacetylide 3 (2 equiv) was added to a soln of 1-iodoadamantane (100 mg, 0.38 mmol, 1 equiv) in anhyd N-methylmorpholine (3 mL), and the resulting suspension was heated at reflux under argon in the dark for 16–24 h. The solvent was removed under reduced pressure, and the residue was diluted with CH2Cl2 (ca. 3 mL). The mixture was passed through Celite, and the filtrate was washed with 0.1 M aq NaN3 (20 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, petroleum ether (40–60 °C)] to afford the product, which was then recrystallized (petroleum ether).

3.5.13.1.1.1.2 Variation 2: Reactions of Alkenylsilver Compounds with Alkyl Halides

In their studies of the mechanism of reactions of organosilver compounds, Casey et al. showed that vinylsilver compounds (e.g., 5), easily obtained by transmetalation from the corresponding Grignard reagents, stereoselectively react with bromomethane.[14,15] The observed retention of stereochemistry suggests a nucleophilic displacement (▶ Scheme 3).

Scheme 3 Nucleophilic Substitution Reaction of a Vinylsilver Compound[14,15]

3.5.13.1.1.2 Method 2: Epoxide Opening with Silver Acetylides

Epoxides are reactive electrophiles that can be readily opened by various nucleophiles including acetylides. Silver acetylides (e.g., 6) are no exception and indeed react with epoxides 7, although activation by dichlorobis (η5-cyclopentadienyl) zirconium (IV) [Zr (Cp)2Cl2] and silver(I) trifluoromethanesulfonate is required.[16] Interestingly, propargylic alcohols 8 and not the classical homopropargylic alcohols are obtained (▶ Scheme 4). The mechanism, as evidenced by NMR studies, involves an epoxide to aldehyde rearrangement before the alkynylation step (▶ Scheme 4). This method is compatible with various functional groups and both electron-rich and -deficient alkynes, and efficiently provides functionalized propargylic alcohols in good to high yields.

Scheme 4 Reaction of Epoxides with Silver Acetylides[16]

R

1

R

2

R

3

Yield (%)

Ref

CH

2

OTHP

(CH

2

)

7

Me

H

82

[

16

]

Bu

(CH

2

)

3

CH=CH

53

[

16

]

CO

2

Me

(CH

2

)

5

54

[

16

]

Bu

(CH

2

)

2

OTBDMS

H

52

[

16

]

CO

2

Me

(CH

2

)

2

OTBDMS

H

46

[

16

]

Propargylic Alcohols 8; General Procedure:[16]

An epoxide 7 (0.5–9.9 mmol, 1 equiv), Zr (Cp)2Cl2 (1.2 equiv), and AgOTf (0.05–0.5 equiv) were added in one portion successively to a stirred soln or suspension of a silver acetylide 6 (1.6 equiv) in CH2Cl2 (1.8–30 mL). The mixture was kept at 23 °C under ambient light and stirred vigorously for 1–10 h. Sat. aq NH4Cl or sat. aq NaHCO3 (0.5–6 mL) was added. The mixture was stirred for 15–30 min and then filtered through a pad of Celite and Na2SO4, which was then washed with Et2O. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by chromatography (silica gel, EtOAc/hexanes).

3.5.13.1.2 Nucleophilic Addition via Organosilver Compounds

3.5.13.1.2.1 Method 1: Alkynylation of Carbonyl Derivatives with Silver Acetylides

Silver acetylides can react as nucleophiles with a wide range of electrophilic partners. Among them, activated carbonyl and related iminium derivatives are reactive enough to be alkynylated either with a preformed silver acetylide in stoichiometric reactions or with in situ formed silver acetylides in catalytic reactions.

3.5.13.1.2.1.1 Variation 1: Reactions of Silver Acetylides with Acyl Halides

An early example is the formation of ynones 10 by addition of silver acetylides (e.g., 9) to acyl halides (▶ Scheme 5).[17] The poor nucleophilicity of silver acetylides allows monoaddition to this type of electrophile to afford the ketone product. This reaction can also be used for the formation of γ-acetoxy ynones (entries 3 and 4)[18,19] and γ-oxo alkynoic esters (entry 5).[20]

Scheme 5 Reaction of Acyl Halides with Silver Acetylides[17,19,20]

Entry

R

1

R

2

Conditions

Yield (%)

Ref

1

Bu

Me

CCl

4

, reflux

42

[

17

]

2

Bu

Ph

AlCl

3

, CCl

4

,0 °C

72

[

17

]

3

CH(OAc)Me

Me

CH

2

Cl

2

, rt

64

[

19

]

4

Me

CH

2

Cl

2

, rt

70

[

19

]

5

CO

2

Me

Cy

CCl

4

, reflux, 3 h

89

[

20

]

Such nucleophilic additions are mild enough to be applied as a key step in total synthesis, as shown by the syntheses of the macrolide antibiotic (+)-methynolide (11)[21] and monosporascone (12),[22] an inhibitor of monoamine oxidase (▶ Scheme 6).

Scheme 6 Applications in Total Synthesis of Reactions of Acyl Halides with Silver Acetylides[21,22]

Ynones 10; General Procedure:[17]

To a stirred soln of a silver acetylide 9 (0.28 mmol, 1 equiv) in CCl4 (250 mL) (CAUTION:toxic) was added an acyl chloride (1.04 equiv), and the resulting light-yellow soln was heated at reflux for 5.5 h. The mixture was cooled, poured over ice, and stirred, and then 10% aq HCl (100 mL) was added and the entire mixture was filtered. The layers were separated and the organic layer was washed with 5 M aq K2CO3 (100 mL) and H2O (2 × 100 mL), dried (CaCl2), and filtered. The residue was distilled under reduced pressure.

Ynones 10; General Procedure by Acylation with Aluminum Trichloride:[17]

CAUTION:

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

To a stirred mixture of AlCl3 (1.15 equiv) in CCl4 (100 mL) (CAUTION:toxic) was added slowly at 0 °C a soln of an acyl chloride (1.25 equiv) in CCl4. A soln of a silver acetylide 9 (0.23 mmol, 1 equiv) in CCl4 (240 mL) was then added over a period of 2 h at the same temperature. The extremely dark mixture was cooled, poured over ice, and stirred, and then 10% aq HCl (100 mL) was added and the entire mixture was filtered. The layers were separated and the organic layer was washed with 5 M aq K2CO3 (100 mL) and H2O (2 × 100 mL), dried (CaCl2), and filtered. The residue was distilled under reduced pressure.

3.5.13.1.2.1.2 Variation 2: Reactions of Silver Acetylides with Aldehydes and Ketones

In a process that is more efficient than the direct alkylation of ketones or aldehydes with lithium acetylides, the addition of silver acetylides (e.g., 13) to carbonyl compounds leads to propargylic alcohols 14 under neutral conditions in the presence of dichlorobis (η5-cyclopentadienyl) zirconium (IV) [Zr (Cp)2Cl2] (1.2 equiv) (▶ Scheme 7).[23] This reaction involves a transmetalation rather than a direct addition of a silver acetylide to a ketone or aldehyde. It has been applied to the total synthesis of the potent anticancer natural product FR901 464.[24]

Scheme 7 Reaction of a Silver Acetylide with Aldehydes and Ketones in the Presence of Silver and Zirconium Catalysts[23]

R

1

R

2

dr(

syn

/

anti

)

Yield (%)

Ref

–

71

[

23

]

H

5.5:1

59

[

23

]

H

6:1

76

[

23

]

CH

2

NHFmoc

H

–

93

[

23

]

4-O

2

NC

6

H

4

H

–

68

[

23

]

(3-Methoxy-3-oxoprop-1-ynyl) silver (13; 1.6 equiv) and Zr (Cp)2Cl2 (1.2 equiv) were added to a soln of an aldehyde (1 mmol) in anhyd CH2Cl2 (3.4 mL) under N2 at 23 °C. AgOTf (0.2 equiv) was added at 23 °C and the mixture was stirred at the same temperature for 2–7 h. Sat. aq NaHCO3 (1.0 mL) was added, and the mixture was stirred for 5 min and then filtered through a pad of Celite. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography (silica gel).

3.5.13.1.2.1.3 Variation 3: Reactions of In Situ Formed Silver Acetylides with Aldehydes and Ketones

Interestingly, similar nucleophilic additions to provide propargylic alcohols 16 can be achieved under catalytic conditions, the silver acetylide being in situ produced from terminal alkynes 15 in the presence of an appropriate silver catalyst and a base (▶ Scheme 8).[25] Although almost insensitive to electronic effects, the reaction is very sensitive to the conditions and the catalyst. (Tricyclohexylphosphine) silver(I) chloride, mild bases such as N, N-diisopropylethylamine, and protic solvents provide the best combination, probably both for solubility and reactivity reasons linked to the in situ formed silver acetylide.

Scheme 8 Reaction of Alkynes with Aldehydes in the Presence of a Silver Catalyst[25]

R

1

R

2

Conditions

Yield (%)

Ref

Ph

2-BrC

6

H

4

60 °C, 12 h

90

[

25

]

Ph

2,5-(MeO)

2

C

6

H

3

90 °C, 12 h

82

[

25

]

Ph

Cy

70 °C, 2 d

81

[

25

]

Ph

2-F

3

CC

6

H

4

80 °C, 6 h

93

[

25

]

(CH

2

)

5

Me

2-F

3

CC

6

H

4

90 °C, 1.5 d

77

[

25

]

In the same way, alkynylation of isatin derivatives 18 as well as trifluoromethyl ketones 20 with terminal alkynes can be achieved in excellent yields, using a catalytic amount (1–2 mol%) of a light-stable silver(I)–bis (N-heterocyclic carbene) complex 17 under air, to provide 3-alkynyl-3-hydroxyindolin-2-one derivatives 19 and trifluoromethyl propargylic alcohols 21, respectively (▶ Scheme 9).[26]

Scheme 9 Reaction of Alkynes with Isatins and Ketones in the Presence of a Silver Catalyst[26]

Ar

1

R

1

Yield (%)

Ref

4-FC

6

H

4

H

95

[

26

]

4-FC

6

H

4

OMe

92

[

26

]

4-MeOC

6

H

4

H

96

[

26

]

R

1

Ar

1

Yield (%)

Ref

4-FC

6

H

4

Ph

94

[

26

]

4-MeOC

6

H

4

Ph

97

[

26

]

(CH

2

)

2

Ph

4-FC

6

H

4

90

[

26

]

Propargylic Alcohols 16; General Procedure:[25]

AgCl (PCy3) (0.025 mmol, 5 mol%) was mixed with H2O (2 mL), an alkyne 15 (1 mmol, 2 equiv), and iPr2NEt (0.1 mmol, 20 mol%). The mixture was stirred at rt until all solid had disappeared. An aldehyde (0.5 mmol) was added, and the mixture was stirred for 5 min, and then heated for the indicated time, cooled, and extracted with Et2O (3 × 5 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by chromatography (silica gel, hexanes/EtOAc).

1,1,1-Trifluorobut-3-yn-2-ols 21; General Procedure:[26]

A vial was charged with NHC–Ag complex 17 (1 mol%), a trifluoromethyl ketone 20 (0.25 mmol), an alkyne (1.5 equiv), and H2O (1 mL). The mixture was stirred at 60 °C for 15 h, and then allowed to cool to rt. The aqueous layer was extracted with EtOAc (2 × 10 mL), and the combined organic layers were washed with brine (20 mL), dried (MgSO4), filtered, and concentrated. The crude product was purified by recrystallization or flash chromatography (silica gel).

3.5.13.1.2.1.4 Variation 4: Reactions of Silver Acetylides with Oxonium Intermediates

Alkynyl glycosides can be obtained upon addition of silver acetylides (e.g., 23) to oxonium intermediates such as 24 that are in situ produced from glycosyl halides.[27–29] In the case of glycosyl halides, silver probably also acts as the halide abstractor, facilitating the formation of the intermediate and reactive oxonium species (▶ Scheme 10). For example, direct alkynylation of β-ribosyl chloride 22 affords both anomers of product 25 in 60% yield with a 3:1 β/α ratio. The course of the reaction depends on the protecting group at O-2 of the ribosyl moiety. Indeed, use of an ester such as benzoyl as protecting group gives the 1,2-O-α-[(2-methoxycarbonyl) ethynyl]benzylidene derivative, whereas the 1,2-O-acetal affords the desired C-glycosides.[27]

Scheme 10 Reaction of a Silver Acetylide with a Glycoside[28]

Ethyl 3-[(3aR,4R,6aS)-2,2-Dimethyl-6-(trityloxymethyl) tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]propynoate (25):[28]

A suspension of (3-ethoxy-3-oxoprop-1-ynyl) silver (23; 20 equiv; derived from ethyl propynoate) in a mixture of anhyd benzene (40 mL) (CAUTION:carcinogen) and CH2Cl2 (10 mL) was stirred for 20 min at rt in the absence of light. The crystalline β-ribosyl chloride 22 (10 mmol, 1 equiv) was then added and the mixture was stirred for a further 40 h, and then diluted with CH2Cl2 and filtered. The filtrate was concentrated to afford a thick syrup, which partially dissolved on warming with Et2O to leave an oil, which was removed by filtration through silica gel. The filtrate was concentrated and the residue was purified by chromatography (silica gel, petroleum ether/EtOAc 10:1); yield: 60%; ratio (β/α) 3:1.

3.5.13.1.2.1.5 Variation 5: Reactions of Silver Acetylides with Carbon Dioxide

Carbon dioxide is an electrophile and, provided that an appropriate ligand is added to depolymerize and solubilize the silver acetylide used, it readily reacts with the latter. In the presence of tributylphosphine or tert-butyl isocyanide in warm tetrahydrofuran, acetylenic carboxylates can be produced and trapped with iodomethane, yielding the corresponding esters (e.g., 26) in good yields (▶ Scheme 11).[30]

Scheme 11 Reaction of a Silver Acetylide with Carbon Dioxide[30]

Twenty years later, the first catalytic process was described by Inoue.[31] The initial report employed 1 mol% of silver(I) iodide in combination with 1.5 equivalents of cesium carbonate in dimethylformamide at 50 °C under a carbon dioxide atmosphere (2 bars);[32] the reaction conditions were later improved by the addition of dimethyl sulfoxide instead of dimethylformamide (▶ Scheme 12).[33] In the latter conditions, electron-rich and -deficient alkynes 27 are efficiently converted into substituted acetylenic acids 28. This reaction can also be performed with a polymer-supported NHC–silver complex.[34] The method benefits from the high activity, stability, and reusability of the heterogeneous catalyst; however, the process still needs the addition of cesium carbonate.

Scheme 12 Reaction of Alkynes with Carbon Dioxide[33]

R

1

Yield (%)

Ref

Cy

99

[

33

]

cyclopropyl

95

[

33

]

Ph

99

[

33

]

2-MeOC

6

H

4

99

[

33

]

4-F

3

CC

6

H

4

98

[

33

]

4-Me

2

NC

6

H

4

96

[

33

]

2-pyridyl

40

[

33

]

As mentioned above, silver carboxylates can be alkylated in situ, leading to esters. Indeed, Anastas and co-workers reported a cascade sequence involving the in situ formation of silver acetylides 30 from arylacetylenes 29, trapping with carbon dioxide, the alkylation of the thus-formed carboxylate 31 with bromides 32, and the Diels–Alder-type cyclization of the diynes 33 (▶ Scheme 13). This reaction offers a new access to naphthalenyl lactones 34 and 35 from very simple starting materials.[35]

Scheme 13 Reaction of Alkynes with Carbon Dioxide in the Presence of a Silver Catalyst[35]

R

1

R

2

R

3

R

4

Ratio (

34

/

35

)

Yield (%)

Ref

OMe

H

H

H

55:45

51

[

35

]

Me

H

OMe

H

58:42

34

[

35

]

Me

Me

H

Me

59:41

56

[

35

]

H

OMe

H

OMe

82:18

49

[

35

]

H

CF

3

H

CF

3

0:100

39

[

35

]

More recently, silver(I) tungstate (Ag2WO4) was also reported as a catalyst for the conversion of alkynes into propynoic esters. Indeed, only 0.25 mol% of the silver catalyst is necessary with cesium carbonate and haloalkanes in dimethylformamide under carbon dioxide atmosphere.[36] The synergistic effect of silver acetylide and tungstate anion activation of carbon dioxide allows the reaction to be performed at room temperature.

Propynoic Acids 28; General Procedure:[33]

A 10-mL vessel was charged with Cs2CO3 (1.2 equiv). Under CO2, a soln of AgBF4 (0.05–0.25 equiv) in degassed DMSO (3 mL) was added, and the mixture was stirred at rt for 5 min. The vessel was purged with CO2. An alkyne 27 (1 mmol) was added, and the mixture was stirred at ambient CO2 pressure for 16 h at 50 °C and then cooled to rt. The solvent was removed by lyophilization. The resulting salt was dissolved in H2O (10 mL) and the soln was extracted with hexane (3 × 20 mL). The aqueous layer was acidified with 1 M aq HCl (2 mL) and extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with brine (10 mL), dried (MgSO4), filtered, and concentrated under reduced pressure.

Lactones 34 and 35; General Procedure:[35]

AgI (0.1 equiv) was introduced into aflask fittedwith a condenser under CO2 (1 atm). DMA (1 mL), K2CO3 (1.16 equiv), an arylacetylene 29 (1 mmol, 1 equiv), and 3-bromo-1-phenylprop-1-yne (32; 1 equiv) were added. The stirred mixture was heated at 100 °C for 8 h, then cooled, and extracted with EtOAc. The extract was concentrated and the residue was purified by chromatography (silica gel, EtOAc/hexane 1:5).

3.5.13.1.2.2 Method 2: Alkynylation of Imine Derivatives with Silver Acetylides

3.5.13.1.2.2.1 Variation 1: Reactions of Silver Acetylides with Imidoyl Chlorides

Preformed silver acetylides can react with imidoyl chlorides leading to ynimines (e.g., 37) in good yields. The latter can be cyclized to afford pyrazoles upon treatment with hydrazine.[37] As for glycosyl halides (see ▶ Section 3.5.13.1.2.1.4), silver probably also acts as halide abstractor, furnishing an intermediate nitrilium species (e.g., 36) (▶ Scheme 14).

Scheme 14 Reaction of Silver Acetylides with Imidoyl Chlorides[37]

3.5.13.1.2.2.2 Variation 2: Reactions of Silver Acetylides with Iminium Salts

It is well-known that pyridine and related heterocycles can undergo nucleophilic addition upon nitrogen activation. Thus, it is not so surprising that pre- or in situ formed silver acetylides react with pyridinium and quinolinium salts 38 after N-benzoylation,[38] N-benz-oyloxylation,[39] or N-phenoxycarbonylation (▶ Scheme 15).[40] Similar behavior is described for the reaction of cotarnine hydrochloride, a 2-methyl-3,4-dihydroisoquinolin-2-ium salt, with silver acetylides in refluxing acetonitrile.[41] Examples for the preparation of phenyl 2-alkynylquinoline-1(2H)-carboxylates 41 from (trimethylsilyl) alkynes 40 and phenoxycarbonylated quinolines 39 are shown in ▶ Scheme 16.[40]

Scheme 15 Reactions of Silver Acetylides with Pyridinium and Quinolinium Salts[38–41]

Scheme 16 Reaction of Silver Acetylides with Phenoxycarbonylated Quinolines[40]

R

1

R

2

R

3

R

4

Yield (%)

Ref

H

H

H

Ph

91

[

40

]

CN

H

H

Ph

97

[

40

]

Me

H

H

Ph

96

[

40

]

H

CHO

H

Ph

85

[

40

]

H

H

NO

2

Ph

77

[

40

]

CN

H

H

Bu

90

[

40

]

Phenyl 2-Alkynylquinoline-1(2H)-carboxylates 41; General Procedure:[40]

Phenyl chloroformate (1.2 equiv) was added to a soln of a quinoline 39 (1 mmol, 1 equiv) in anhyd 1,2-dichloroethane (5 mL) at 0 °C. The mixture was stirred for 1 h. A (trimethylsilyl) alkyne 40 (2 equiv) and AgOTf (1.2 equiv) were added and the mixture was heated at 83 °C for 4 h and then filtered. The filtrate was washed with 2 M aq NaOH, dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by chromatography (silica gel).

3.5.13.1.2.2.3 Variation 3: Addition Reaction between Alkynes and Imines Promoted by Silver

Catalytic versions of the addition of silver acetylides to imines or iminium salts have also been established. Thus, in the presence of silver salts in apolar solvents, terminal alkynes 42 add to α-imino esters 43 derived from ethyl glyoxylate in a mild and efficient way to provide amino esters 44 (▶ Scheme 17).[42] In these reactions, the starting imine is probably acting as a base for forming the silver acetylide. An elegant enantioselective version of this reaction was developed by Rueping;[43] the combination of silver(I) acetate and a 1,1′—bi-2-naphthol phosphate derivative gave enantiomeric ratios up to 96:4.

Scheme 17 Reaction of Silver Acetylides with an Imine[42]

R

1

Yield (%)

Ref

Ph

93

[

42

]

(CH

2

)

2

Ph

87

[

42

]

Bu

84

[

42

]

(CH

2

)

5

Me

91

[

42

]

CH

2

TMS

79

[

42

]

In the derivatization of dibenzooxazepines 46, a wide variety of alkynes 47 can be efficiently added in the presence of the chiral silver salt of phosphoric acid 45 to furnish 11-alkynyl-10,11-dihydrodibenzo[b, f][1,4]oxazepines 48 with high enantioselectivity (▶ Scheme 18).[44]

Scheme 18 Asymmetric Alkynylation of Dibenzooxazepines[44]

R

1

R

2

Yield (%)

ee (%)

Ref

H

Ph

87

87

[

44

]

H

92

95

[

44

]

H

CMe=CH

2

74

91

[

44

]

H

C≡CPh

84

85

[

44

]

Me

92

97

[

44

]

F

96

99

[

44

]

11-Alkynyl-10,11-dihydrodibenzo[b,f][1,4]oxazepines 48; General Procedure:[44]

To the mixture of a dibenzo[b, f][1,4]oxazepine 46 (0.2 mmol), AgOAc (5 mol%), and chiral phosphoric acid catalyst 45 (10 mol%) in dioxane (2 mL) was added an alkyne 47 (2 equiv). This mixture was stirred at 15 °C for 72–120 h and directly subjected to column chromatography (silica gel, petroleum ether/EtOAc 40:1 to 20:1).

3.5.13.1.2.2.4 Variation 4: A3 Coupling Promoted by Silver

Three-component coupling reactions between aldehydes, alkynes, and amines (A3 coupling) can be efficiently catalyzed by silver salts in water or ionic liquids. Depending on the substrates, heating up to 100 °C may be required. This reaction provides the corresponding propargylic amines 49 usually in good to high yields (▶ Scheme 19).[45,46] However, when a hydroxy or alkoxy group is present in the aldehyde, the reaction does not readily occur because a chelate can be formed, leading to side reactions.[47]

Scheme 19 Three-Component Coupling Reactions Catalyzed by Silver(I) Iodide[45]

R

1

n

Yield (%)

Ref

Ph

1

95

[

45

]

Ph

2

70

[

45

]

Cy

3

96

[

45

]

(CH

2

)

2

Ph

2

85

[

45

]

The same reaction was reported with supported silver catalysts, using supports as diverse as amorphous silica gel and alumina, diatomite, and multiwall nanotubes. All of them were obtained by immobilization of silver(I) oxide on the corresponding supports. The best yields are achieved with silver(I) oxide on alumina; however, this support does not allow useful recycling, due to leaching.[48]

Propargylamines 49; General Procedure:[45]

A mixture of AgI (1.5–3 mol%), an aldehyde (2 mmol, 1 equiv), an amine (1.1 equiv), and phenylacetylene (1.5 equiv) in H2O (1 mL) was stirred at 100 °C for 2 h under N2. The mixture was cooled and extracted with Et2O (3 × 15 mL). The combined extracts were dried (MgSO4), filtered, and concentrated. The residue was purified by chromatography (silica gel, hexanes/EtOAc).

3.5.13.1.2.3 Method 3: Decarboxylative Addition of Arenecarboxylic Acids to Aldehydes and Imine Derivatives

Arenecarboxylic acids can be decarboxylated upon heating in the presence of silver salts, or a combination of silver and palladium salts. Organosilver compounds are probably formed in this process (see ▶ Section 3.5.13.6