Science of Synthesis Knowledge Updates 2012 Vol. 2 E-Book

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

Seitenzahl: 966

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.

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. 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

4.4.25.11 Acylsilanes

M. Nahm Garrett and J. S. Johnson

This chapter is an update to the previous Science of Synthesis contribution on the synthesis and applications of acylsilanes. It covers syntheses and applications reported since 2000. Synthetic methods described herein are divided according to five target product subtypes: simple acylsilanes, bis(acylsilanes), α-oxo acylsilanes, α,β-unsaturated acylsilanes, and α-amino acylsilanes. The largest of those sections, simple acylsilanes, is further divided according to the main strategies used for their synthesis: hydrolysis of acetals, oxidation of organocuprates, and acyl substitution of carboxylic amides. The major applications of the various types of acylsilanes are also described.

Keywords: acylsilanes · dithianes · hydrolysis · cuprates · oxidation · amides · substitution · bis(acylsilanes) · nucleophilic addition · Brook rearrangement · acyl anion equivalent

8.1.34 Asymmetric Lithiation

J.-C. Kizirian

This section deals with processes that produce a chiral lithiated species by an asymmetric lithiation. The lithium atom can be introduced on an sp3 carbon atom (centered chirality) or an sp2 carbon atom (axial or planar chirality). The C—Li bond can be formed by one of three main methods: deprotonation (of a C—H bond), transmetalation (usually from tin), or reductive lithiation (from halo, cyano, arylsulfanyl, arylselanyl, or aryltellanyl derivatives). The configurational stability of the lithiated species determines the stereochemical pathway of the reaction, but is not a necessary condition to have a selective process. The product is formed by one of the following mechanisms: enantioselective deprotonation, dynamic thermodynamic resolution, or dynamic kinetic resolution. Furthermore, the electrophilic substitution step can take place with inversion or retention of configuration.

Keywords: lithium compounds · dynamic thermodynamic resolution · dynamic kinetic resolution · enantioselective deprotonation · diastereoselective deprotonation · Wittig rearrangement · tin–lithium exchange · reductive lithiation · carbolithiation

13.32 Product Class 32: 1,2,3-Trithioles, Their Benzo Derivatives, and Selenium and Tellurium Analogues

R. A. Aitken

This chapter covers methods for the synthesis of 1,2,3-trithioles, 1,2,3-benzotrithioles, and a range of eleven different analogues with one or more sulfur atoms replaced by selenium or tellurium. None of these ring systems has previously been included in Science of Synthesis.

Keywords: sulfur heterocycles · selenium compounds · tellurium compounds · trithioles · dithiatelluroles · benzotrithioles · benzodithiaselenoles · benzothiadiselenoles · benzotriselenoles · benzodithiatelluroles · benzothiaselenatelluroles · benzodiselenatelluroles

13.33 Product Class 33: 1,2,4-Triazolium Salts

C. A. Gondo and J. W. Bode

A 1,2,4-triazolium salt is composed of a cationic five-membered ring associated with a negatively charged counterion. These compounds are stable precursors for N-heterocyclic carbenes (NHCs), which are used either as ligands for metal-based catalysts or as organic catalysts. In this survey, the major routes for the synthesis of 1,2,4-triazolium salts are reviewed.

Keywords: heterocycle · N-heterocyclic carbene · ligand · organocatalyst · ring-closure reactions · ring transformation · substituent modification · 1,2,4-triazolium salts

13.34 Product Class 34: Dithiadiazolium Salts and Dithiadiazolyl-Containing Compounds

R. J. Pearson

This chapter describes the preparation of 1,2,3,5-dithiadiazolium salts and their corresponding radicals and dimers. These crystalline and brightly colored compounds are most commonly synthesized, in varying yields, by ring-closure reactions involving amidines, amidoximes, nitriles, azines, and alkenes. The synthetic routes to the less stable 1,3,2,4-isomers are also discussed, together with the conditions for their complete isomerism to the dominant 1,2,3,5-isomers.

Keywords: dithiadiazole · radical · dimerization · isomerism · ring closure · ring transformation

16.4.6 1,4-Dithiins

S. A. Kosarev

This chapter is an update to the earlier Science of Synthesis contribution describing methods for the synthesis of monocyclic 1,4-dithiins and their annulated analogues. It focuses on the literature published in the period 2003–2011.

Keywords: alkynes · chromium catalysts · dihalides · diimides · diketones · 1,4-dithiins · diols · dithianes · dithiols · sulfides · sulfinates · sulfur compounds · sulfur heterocycles · thiadiazoles · thiolates · thiophenes

16.18.7 Pyridopyridazines

S. Lou and J. Zhang

This update presents the state of the art in the synthesis of pyridopyridazine heterocyclic systems from 2001 to 2011. The synthetic methodologies are grouped based on the isomeric pyridopyridazine structures and typical experimental procedures are included. Some pyridopyridazine derivatives have been used as drug candidates and brief discussions are given of their pharmaceutical activities in the treatment of cancers, allergies, pain states, inflammatory diseases, and erectile dysfunction.

Keywords: pyridopyridazine · heterocycles · pyridine · pyridazine · pyridopyridazinone · hydrazine · dicarbonyl

16.19.5 Pyridopyrimidines

Y.-J. Wu

This chapter in an update to the previous Science of Synthesis contribution describing the the synthesis of all four isomeric pyridopyrimidines and their saturated derivatives. It covers syntheses described from 2002 until 2011.

Keywords: pyrido[2,3-d]pyrimidine · pyrido[3,2-d]pyrimidine · pyrido[3,4-d]pyrimidine · pyrido[4,3-d]pyrimidine

16.21.4 Pteridines and Related Structures

T. Ishikawa

This review is an update to the earlier Science of Synthesis contribution describing the synthesis of pteridines and pteridinones. It focuses on syntheses described since 2003.

Keywords: pteridine · pteridinone · ring closure · ring transformation · substituent modification

16.22.6 Other Diazinodiazines

T. Ishikawa

This review is an update to the earlier Science of Synthesis contribution describing the synthesis of diazinodiazines other than pteridines. It focuses on syntheses described since 2003.

Keywords: diazinodiazine · pyridazinopyridazine · pyrimidopyridazine · pyrimidopyrimidine · addition · ring closure · substituent modification

17.2.1.9 1,2,3-Triazines and Phosphorus Analogues

P. Aggarwal and M. W. P. Bebbington

This manuscript is an update to the earlier Science of Synthesis contribution describing methods for the synthesis of 1,2,3-triazines. The reported diazotization method is of particular note, as the substrate scope has broadened in recent years.

Keywords: alkylation · arylation · condensation reactions · cyclization · diazotization · dipolar cycloaddition · nucleophilic aromatic substitution · nucleophilic addition · ring-closure reactions · triazines

17.2.2.3 1,2,4-Triazines

P. Aggarwal and M. W. P. Bebbington

This manuscript is an update to the earlier Science of Synthesis contribution describing methods for the synthesis of 1,2,4-triazines. Of particular note are the microwave-assisted reactions that have emerged in recent years in addition to more conventional methods.

Keywords: condensation reactions · cyclization · dehydration · diazo compounds · microwave-assisted reactions · multicomponent reactions · nucleophilic addition · ring closure · ring formation · 1,2,4-triazines

17.2.3.6 1,3,5-Triazines and Phosphorus Analogues

P. Aggarwal and M. W. P. Bebbington

This manuscript is an update to the earlier Science of Synthesis edition describing methods for the synthesis of 1,3,5-triazines. A number of transition-metal-catalyzed techniques have emerged in recent years to complement traditional methods.

Keywords: condensation reactions · cross-coupling reactions · multicomponent reactions · nucleophilic aromatic substitution · ring closure · ring formation · transition metals · 1,3,5-triazines

34.1.1.7 Synthesis by Substitution of Hydrogen

G. Sandford

Recent methods for the selective fluorination of sp3-hybridized carbon atoms in aliphatic systems by reaction of an electrophilic fluorinating agent with a sufficiently nucleophilic C—H bond via electrophilic aliphatic substitution processes are discussed in this update.

Keywords: organofluorine · electrophilic aliphatic substitution · elemental fluorine · Selectfluor · selective fluorination

Science of Synthesis Knowledge Updates 2012/2

Preface

Abstracts

Table of Contents

4.4.25.11 Acylsilanes (Update 2012)

M. Nahm Garrett and J. S. Johnson

8.1.34 Asymmetric Lithiation

J.-C. Kizirian

13.32 Product Class 32: 1,2,3-Trithioles, Their Benzo Derivatives, and Selenium and Tellurium Analogues

R. A. Aitken

13.33 Product Class 33: 1,2,4-Triazolium Salts

C. A. Gondo and J. W. Bode

13.34 Product Class 34: Dithiadiazolium Salts and Dithiadiazolyl-Containing Compounds

R. J. Pearson

16.4.6 1,4-Dithiins (Update 2012)

S. A. Kosarev

16.18.7 Pyridopyridazines (Update 2012)

S. Lou and J. Zhang

16.19.5 Pyridopyrimidines (Update 2012)

Y.-J. Wu

16.21.4 Pteridines and Related Structures (Update 2012)

T. Ishikawa

16.22.6 Other Diazinodiazines (Update 2012)

T. Ishikawa

17.2.1.9 1,2,3-Triazines and Phosphorus Analogues (Update 2012)

P. Aggarwal and M. W. P. Bebbington

17.2.2.3 1,2,4-Triazines (Update 2012)

P. Aggarwal and M. W. P. Bebbington

17.2.3.6 1,3,5-Triazines and Phosphorus Analogues (Update 2012)

P. Aggarwal and M. W. P. Bebbington

34.1.1.7 Synthesis by Substitution of Hydrogen (Update 2012)

G. Sandford

Author Index

Abbreviations

Table of Contents

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

4.4 Product Class 4: Silicon Compounds

4.4.25.11 Acylsilanes

M. Nahm Garrett and J. S. Johnson

4.4.25.11 Acylsilanes

4.4.25.11.1 Synthesis of Acylsilanes

4.4.25.11.1.1 Method 1: Synthesis of Simple Acylsilanes

4.4.25.11.1.1.1 Variation 1: Hydrolysis of Acetals

4.4.25.11.1.1.2 Variation 2: Oxidation of Organocuprates

4.4.25.11.1.1.3 Variation 3: Nucleophilic Substitution of Morpholine Amides

4.4.25.11.1.1.4 Variation 4: Additional Synthetic Methods

4.4.25.11.1.2 Method 2: Synthesis of Bis(acylsilanes)

4.4.25.11.1.3 Method 3: Synthesis of α-Oxo Acylsilanes

4.4.25.11.1.4 Method 4: Synthesis of α,β-Unsaturated Acylsilanes

4.4.25.11.1.5 Method 5: Synthesis of α-Amino Acylsilanes

4.4.25.11.2 Applications of Acylsilanes

4.4.25.11.2.1 Method 1: Applications of Simple Acylsilanes

4.4.25.11.2.1.1 Variation 1: Nucleophilic Addition

4.4.25.11.2.1.2 Variation 2: Nucleophilic Addition with Brook Rearrangement

4.4.25.11.2.1.3 Variation 3: Acylsilanes as Acyl Anion Precursors

4.4.25.11.2.1.4 Variation 4: Enolate and Enol Ether Reactions

4.4.25.11.2.1.5 Variation 5: Photochemistry

4.4.25.11.2.1.6 Variation 6: Miscellaneous Applications

4.4.25.11.2.2 Method 2: Applications of Bis(acylsilanes)

4.4.25.11.2.3 Method 3: Applications of α-Oxo Acylsilanes

4.4.25.11.2.4 Method 4: Applications of α,β-Unsaturated Acylsilanes

Volume 8: Compounds of Group 1 (Li … Cs)

8.1 Product Class 1: Lithium Compounds

8.1.34 Asymmetric Lithiation

J.-C. Kizirian

8.1.34 Asymmetric Lithiation

8.1.34.1 Method 1: Deprotonation in a Position α to a Heteroatom

8.1.34.1.1 Variation 1: Enantioselective Deprotonation of Carbamates and Their Analogues

8.1.34.1.2 Variation 2: Enantioselective Deprotonation of Phosphorylated Derivatives

8.1.34.1.3 Variation 3: Enantioselective Deprotonation of Ureas

8.1.34.1.4 Variation 4: Enantioselective Deprotonation of Phosphoramidates

8.1.34.1.5 Variation 5: Enantioselective Deprotonation Followed by Transmetalation

8.1.34.1.6 Variation 6: Enantioselective Deprotonation Followed by Cyclization

8.1.34.1.7 Variation 7: Enantioselective Deprotonation Followed by Wittig Rearrangement

8.1.34.1.8 Variation 8: Diastereoselective Deprotonation of Carbamates

8.1.34.1.9 Variation 9: Diastereoselective and Enantioselective Deprotonations of Epoxides or Aziridines

8.1.34.1.10 Variation 10: Catalytic Enantioselective Deprotonation

8.1.34.2 Method 2: Deprotonation in a Position Lacking an α-Heteroatom

8.1.34.2.1 Variation 1: Diastereoselective Deprotonation in a Benzylic Position

8.1.34.2.2 Variation 2: Enantioselective Deprotonation in a Benzylic Position

8.1.34.2.3 Variation 3: Diastereoselective Deprotonation of Metallocene Derivatives

8.1.34.2.4 Variation 4: Enantioselective Deprotonation of Metallocene Derivatives

8.1.34.3 Method 3: Tin–Lithium Exchange

8.1.34.4 Method 4: Reductive Lithiation

8.1.34.5 Method 5: Carbometalation

8.1.34.5.1 Variation 1: Enantioselective Intermolecular Carbolithiation

8.1.34.5.2 Variation 2: Enantioselective and Diastereoselective Intramolecular Carbolithiation

Volume 13: Five-Membered Hetarenes with Three or More Heteroatoms

13.32 Product Class 32: 1,2,3-Trithioles, Their Benzo Derivatives, and Selenium and Tellurium Analogues

R. A. Aitken

13.32 Product Class 32: 1,2,3-Trithioles, Their Benzo Derivatives, and Selenium and Tellurium Analogues

13.32.1 Product Subclass 1: 1,2,3-Trithioles

13.32.1.1 Synthesis by Ring-Closure Reactions

13.32.1.1.1 By Formation of Two S—S Bonds

13.32.1.1.1.1 Method 1: Synthesis from Metal Enedithiolates with Thionyl Chloride

13.32.1.1.2 By Formation of Two C—S Bonds

13.32.1.1.2.1 Method 1: Synthesis from Alkynes with Sulfur

13.32.1.2 Synthesis by Ring Transformation

13.32.1.2.1 Method 1: Formal Germanium/Sulfur Exchange of a 1,3,2-Dithiagermole with Thionyl Chloride

13.32.1.2.2 Method 2: Formal Ring Expansion with the Insertion of an Extra Sulfur Atom

13.32.2 Product Subclass 2: 1,2,3-Benzotrithioles and Other Ring-Fused Analogues

13.32.2.1 Synthesis by Ring-Closure Reactions

13.32.2.1.1 By Formation of Two S—S Bonds and One C—C Bond

13.32.2.1.1.1 Method 1: Electrochemical Reduction of Carbon Disulfide

13.32.2.1.2 By Formation of Two S—S Bonds

13.32.2.1.2.1 Method 1: Synthesis from Arene-1,2-dithiols

13.32.2.1.2.1.1 Variation 1: Reactions with Sulfur Dichloride

13.32.2.1.2.1.2 Variation 2: Reactions with Thionyl Chloride

13.32.2.1.2.1.3 Variation 3: Reactions with Thionyl Chloride, Sodium Iodide, and Perchloric Acid

13.32.2.1.2.2 Method 2: Synthesis from Metal Enedithiolates with Sulfur Dichloride

13.32.2.1.2.2.1 Variation 1: Reactions with Lithium or Sodium Enedithiolates

13.32.2.1.2.2.2 Variation 2: Reactions with Zinc Enedithiolates

13.32.2.1.3 By Formation of Two C—S Bonds

13.32.2.1.3.1 Method 1: Synthesis from 1,2-Dibromoarenes with Sulfur

13.32.2.1.3.1.1 Variation 1: Reactions in Liquid Ammonia

13.32.2.1.3.1.2 Variation 2: Reaction in Diazabicycloundecene

13.32.2.2 Synthesis by Ring Transformation

13.32.2.2.1 Method 1: Synthesis from 1,3,2-Dithiametalloles

13.32.2.2.1.1 Variation 1: Reactions of 1,3,2-Benzodithiatitanoles with Sulfur Dichloride

13.32.2.2.1.2 Variation 2: Reactions of 1,3,2-Benzodithiastannoles with Sulfur Dichloride

13.32.2.2.1.3 Variation 3: Reactions of 1,3,2-Benzodithiastannoles with Thionyl Chloride

13.32.2.2.1.4 Variation 4: Reactions of 1,3,2-Benzodithiastannoles with Thionyl Chloride, Sodium Iodide, and Perchloric Acid

13.32.2.2.1.5 Variation 5: Reactions of 1,3,2-Benzodithiastannoles with Thionyl Chloride, Trimethylsilyl Trifluoromethanesulfonate, and Samarium(II) Iodide

13.32.2.2.2 Method 2: Synthesis from 1,2,3-Benzochalcogenadiazoles with Sulfur

13.32.2.2.2.1 Variation 1: Reactions of 1,2,3-Benzothiadiazoles

13.32.2.2.2.2 Variation 2: Reactions with 1,2,3-Benzoselenadiazoles

13.32.2.2.3 Method 3: Synthesis from 1,3-Benzodithiol-2-ones

13.32.2.2.3.1 Variation 1: Reactions with Sodium Hydrogen Sulfide

13.32.2.2.3.2 Variation 2: Reactions with an Alkyllithium and Sulfur Dichloride

13.32.2.2.3.3 Variation 3: Reactions with a Sodium Alkoxide and Sulfur Dichloride

13.32.2.2.4 Method 4: Synthesis from 1,3-Benzodithiole-2-thiones

13.32.2.2.5 Method 5: Ring Contraction

13.32.2.2.5.1 Variation 1: Synthesis from 1,3,5,2,4-Benzotrithiadiazepines by Thermolysis

13.32.2.2.5.2 Variation 2: Synthesis from Benzopentathiepins

13.32.2.3 Synthesis by Substituent Modification

13.32.2.3.1 One-Electron Oxidation

13.32.2.3.1.1 Method 1: Synthesis from 1,2,3-Benzotrithioles with Nitrosonium Hexafluorophosphate To Give Radical Cationic Salts

13.32.2.3.2 Addition Reactions

13.32.2.3.2.1 Method 1: Synthesis from 1,2,3-Benzotrithioles by Oxidation

13.32.2.3.3 Rearrangement of Substituents

13.32.2.3.3.1 Method 1: Synthesis from 1,2,3-Benzotrithiole 2-Oxides by Photochemical Rearrangement

13.32.3 Product Subclass 3: 1,2,3-Benzodithiaselenoles

13.32.3.1 Synthesis by Ring-Closure Reactions

13.32.3.1.1 By Formation of One S—S and One S—Se Bond

13.32.3.1.1.1 Method 1: Synthesis from 2-(Chlorosulfonyl)benzeneselenenyl Bromide and Thioacetamide

13.32.3.2 Synthesis by Ring Transformation

13.32.3.2.1 Method 1: Synthesis from 1,3,2-Benzothiaselenastannoles

13.32.3.2.1.1 Variation 1: Reactions with Sulfur in Liquid Ammonia

13.32.3.2.1.2 Variation 2: Reactions with Thionyl Chloride, Sodium Iodide, and Perchloric Acid

13.32.4 Product Subclass 4: 1,3,2-Benzodithiaselenoles

13.32.4.1 Synthesis by Ring-Closure Reactions

13.32.4.1.1 By Formation of Two S—Se Bonds

13.32.4.1.1.1 Method 1: Reactions of Arene-1,2-dithiols with Selenium Dioxide

13.32.4.2 Synthesis by Ring Transformation

13.32.4.2.1 Method 1: Reactions of 1,3,2-Benzodithiastannoles with Selenium Oxychloride, Trimethylsilyl Trifluoromethanesulfonate, and Samarium(II) Iodide

13.32.5 Product Subclass 5: 1,2,3-Benzothiadiselenoles

13.32.5.1 Synthesis by Ring Transformation

13.32.5.1.1 Method 1: Synthesis from 1,3,2-Benzothiaselenastannoles with Selenium Oxychloride, Trimethylsilyl Trifluoromethanesulfonate, and Samarium(II) Iodide

13.32.5.1.2 Method 2: Ring Contraction of Dibenzo-1,2,5,6- and 1,5,2,6-Dithiadiselenocins by Photolysis

13.32.6 Product Subclass 6: 2,1,3-Benzothiadiselenoles

13.32.6.1 Synthesis by Ring Transformation

13.32.6.1.1 Method 1: Synthesis from 1,3,2-Benzodiselenastannoles

13.32.6.1.1.1 Variation 1: Reactions with Sulfur in Liquid Ammonia

13.32.6.1.1.2 Variation 2: Reactions with Thionyl Chloride, Sodium Iodide, and Perchloric Acid

13.32.6.1.2 Method 2: Synthesis from 1,2,3-Benzotriselenoles with Sulfur

13.32.7 Product Subclass 7: 1,2,3-Benzotriselenoles

13.32.7.1 Synthesis by Ring-Closure Reactions

13.32.7.1.1 By Formation of Two Se—Se Bonds

13.32.7.1.1.1 Method 1: Synthesis from Dilithium Arene-1,2-diselenolates with Selenium Tetrachloride

13.32.7.1.1.2 Method 2: Synthesis from Benzene-1,2-diselenenyl Dichloride with Selenium

13.32.7.1.2 By Formation of Two Se—C Bonds

13.32.7.1.2.1 Method 1: Synthesis from 1,2-Dibromoarenes with Selenium

13.32.7.1.2.2 Method 2: Reactions of Tribenzo-1,4,7-trimercuronins with Selenium

13.32.7.2 Synthesis by Ring Transformation

13.32.7.2.1 Method 1: Synthesis from 1,3,2-Benzodiselenastannoles

13.32.7.2.1.1 Variation 1: Reactions with Selenium Oxychloride, Trimethylsilyl Trifluoromethanesulfonate, and Samarium(II) Iodide

13.32.7.2.1.2 Variation 2: Reaction with Selenium Tetrachloride

13.32.7.2.2 Method 2: Reactions of 1,2,3-Benzoselenadiazoles with Selenium

13.32.7.2.3 Method 3: By Ring Contraction

13.32.7.2.3.1 Variation 1: Synthesis from Dibenzo-1,2,5,6-tetraselenocins by Photolysis

13.32.7.2.3.2 Variation 2: Synthesis from Dibenzo-1,2,5,6-tetraselenocin with Diselenium Dichloride

13.32.7.3 Synthesis by Substituent Modification

13.32.7.3.1 One-Electron Oxidation

13.32.7.3.1.1 Method 1: Synthesis from 1,2,3-Benzotriselenoles with Nitrosonium Hexafluorophosphate To Give Radical Cationic Salts

13.32.8 Product Subclass 8: 1,2,3-Benzodithiatelluroles

13.32.8.1 Synthesis by Ring Transformation

13.32.8.1.1 Method 1: Synthesis from 1,3,2-Benzothiatelluratitanoles with Sulfur Dichloride

13.32.9 Product Subclass 9: 1,3,2-Dithiatelluroles and 1,3,2-Benzodithiatelluroles

13.32.9.1 Synthesis by Ring-Closure Reactions

13.32.9.1.1 By Formation of Two S—Te Bonds

13.32.9.1.1.1 Method 1: Synthesis from Arene-1,2-dithiols with Tellurium Tetrachloride

13.32.9.1.1.2 Method 2: Synthesis from Metal Enedithiolates

13.32.9.1.1.2.1 Variation 1: Reactions with Tellurium Tetrahalides

13.32.9.1.1.2.2 Variation 2: Reactions with Sodium Tellurapentathionate

13.32.9.2 Synthesis by Ring Transformation

13.32.9.2.1 Method 1: Synthesis from 1,3,2-Benzodithiastannoles with Tellurium Tetrachloride

13.32.10 Product Subclass 10: 1,2,3-Benzothiaselenatelluroles

13.32.10.1 Synthesis by Ring Transformation

13.32.10.1.1 Method 1: Synthesis from 1,3,2-Benzothiatelluratitanoles with Selenium Oxychloride

13.32.11 Product Subclass 11: 1,3,2-Benzothiaselenatelluroles

13.32.11.1 Synthesis by Ring Transformation

13.32.11.1.1 Method 1: Synthesis from 1,3,2-Benzothiaselenastannoles with Tellurium Tetrachloride

13.32.12 Product Subclass 12: 2,1,3-Benzothiaselenatelluroles

13.32.12.1 Synthesis by Ring Transformation

13.32.12.1.1 Method 1: Synthesis from a 1,3,2-Benzoselenatelluratitanole with Sulfur Dichloride

13.32.13 Product Subclass 13: 1,2,3-Benzodiselenatelluroles

13.32.13.1 Synthesis by Ring Transformation

13.32.13.1.1 Method 1: Synthesis from 1,3,2-Benzoselenatelluratitanoles with Selenium Oxychloride

13.32.14 Product Subclass 14: 1,3,2-Benzodiselenatelluroles

13.33 Product Class 33: 1,2,4-Triazolium Salts

C. A. Gondo and J. W. Bode

13.33 Product Class 33: 1,2,4-Triazolium Salts

13.33.1 Synthesis by Ring-Closure Reactions

13.33.1.1 By Formation of Two N—C Bonds

13.33.1.1.1 Formation of the N2—C3 and N4—C5 Bonds

13.33.1.1.1.1 Method 1: Reaction of an Imidoyl Chloride with an N-Formylhydrazine

13.33.1.1.2 Formation of the N1—C5 and N4—C5 Bonds

13.33.1.1.2.1 Method 1: Reaction of an α-Aminohydrazone with a Trialkyl Orthoformate

13.33.1.1.2.1.1 Variation 1: Reaction Using a One-Pot Protocol

13.33.1.1.2.1.2 Variation 2: Reaction Using an Electron-Deficient Arylhydrazine

13.33.1.1.2.1.3 Variation 3: Synthesis of N-Mesityl-Substituted Triazolium Salts

13.33.1.1.2.1.4 Variation 4: Reaction Using Dimethyl Sulfate as the Amide-Activating Agent

13.33.1.1.2.1.5 Variation 5: Synthesis of 2-Alkyl-[1,2,4]triazolo[4,3-a]pyridinium Salts

13.33.1.1.2.1.6 Variation 6: Synthesis of 2-Aryl-[1,2,4]triazolo[4,3-a]pyridinium Salts

13.33.2 Synthesis by Ring Transformation

13.33.2.1 Formal Exchange of Ring Members with Retention of Ring Size

13.33.2.1.1 Method 1: Synthesis from 1,3,4-Oxadiazolium Salts

13.33.2.1.2 Method 2: Synthesis from 1,3,4-Thiadiazolium Salts

13.33.3 Synthesis by Substituent Modification

13.33.3.1 Addition Reactions

13.33.3.1.1 Addition of Organic Groups

13.33.3.1.1.1 Method 1: Alkylation Using an Alkyl Chloride, Bromide, or Iodide

13.33.3.1.1.2 Method 2: Alkylation Using a Trialkyloxonium Tetrafluoroborate

13.33.3.2 Modification of Substituents

13.33.3.2.1 Method 1: Paal–Knorr Pyrrole Synthesis Using an Amine-Functionalized Triazolium Salt

13.33.3.2.2 Method 2: Modification by Anion Exchange

13.33.3.2.2.1 Variation 1: Of 1,2,4-Triazolium Halides

13.33.3.2.2.2 Variation 2: With Silver Salts

13.34 Product Class 34: Dithiadiazolium Salts and Dithiadiazolyl-Containing Compounds

R. J. Pearson

13.34 Product Class 34: Dithiadiazolium Salts and Dithiadiazolyl-Containing Compounds

13.34.1 Product Subclass 1: 1,2,3,5-Dithiadiazolium Salts and Related Compounds

13.34.1.1 Synthesis by Ring-Closure Reactions

13.34.1.1.1 By Formation of One S—S and Two S—N Bonds

13.34.1.1.1.1 Method 1: Synthesis from Amidines Using Sulfur Halides

13.34.1.1.1.1.1 Variation 1: Reaction of Amidinium Salts with Sulfur Dichloride and 1,8-Diazabicyclo[5.4.0]undec-7-ene

13.34.1.1.1.1.2 Variation 2: Reaction of Amidinium Salts with Sulfur Monochloride

13.34.1.1.1.1.3 Variation 3: Reaction of N, N, N′-Tris(trimethylsilyl)amidines with Sulfur Dichloride

13.34.1.1.1.2 Method 2: Reaction of Amidoximes with Sulfur Dichloride

13.34.1.1.2 By Formation of One S—S, One S—N, and One N—C Bond

13.34.1.1.2.1 Method 1: Synthesis from Nitriles

13.34.1.1.2.1.1 Variation 1: Reaction with Sulfur Dichloride and Ammonium Chloride

13.34.1.1.2.1.2 Variation 2: Reaction with Trithiazyl Trichloride

13.34.1.1.2.2 Method 2: Synthesis from Azines Using Trithiazyl Trichloride

13.34.1.1.3 By Formation of One S—S and Two N—C Bonds

13.34.1.1.3.1 Method 1: Synthesis from Alkenes Using Trithiazyl Trichloride

13.34.1.2 Synthesis by Ring Transformation

13.34.1.2.1 Method 1: Synthesis by One-Electron Reduction Using Zinc/Copper or Triphenylstibine

13.34.1.2.2 Method 2: Synthesis from 1,3-Dichloro-1,3,2,4,6-dithiatriazines by Thermolytic Ring Contraction

13.34.2 Product Subclass 2: 1,3,2,4-Dithiadiazolium Salts and Related Compounds

13.34.2.1 Synthesis by Ring-Closure Reactions

13.34.2.1.1 By Formation of One S—N and One S—C Bond

13.34.2.1.1.1 Method 1: Synthesis from Nitriles with Dithionitronium Hexafluoroarsenate

13.34.2.1.2 By Formation of One S—N and One N—C Bond

13.34.2.1.2.1 Method 1: Synthesis from Bifunctional Acyl Chlorides with an N, N′-Bis(trimethylsilyl)sulfur Diimide

13.34.2.2 Synthesis by Ring Transformation

13.34.2.2.1 Method 1: Synthesis by One-Electron Reduction Using Triphenylstibine

13.34.2.2.2 Method 2: Synthesis from a Dithiadiazastannole Using Carbonyl Difluoride

13.34.2.3 Synthesis by Substituent Modification

13.34.2.3.1 Method 1: Synthesis by O-Alkylation Using Methyl Fluorosulfonate

Volume 16: Six-Membered Hetarenes with Two Identical Heteroatoms

16.4 Product Class 4: 1,4-Dithiins

16.4.6 1,4-Dithiins

S. A. Kosarev

16.4.6 1,4-Dithiins

16.4.6.1 Synthesis by Ring-Closure Reactions

16.4.6.1.1 By Formation of Four S—C Bonds

16.4.6.1.1.1 Fragments C—C, C—C, and Two S Fragments

16.4.6.1.1.1.1 Method 1: Synthesis from (Z)-1,2-Dichloroethene and Sodium Sulfide

16.4.6.1.1.1.2 Method 2: Synthesis from Alkynes and Sulfur

16.4.6.1.2 By Formation of Two S—C Bonds

16.4.6.1.2.1 Fragments C—C—S—C—C and S

16.4.6.1.2.1.1 Method 1: Synthesis from 1-Bromo-4-phenoxybut-2-yne and Sodium Sulfide

16.4.6.1.2.2 Fragments S—C—C—S and C—C

16.4.6.1.2.2.1 Method 1: Synthesis from 1,2-Dihydroxyarenes and 1,2-Dithiols

16.4.6.1.2.2.2 Method 2: Synthesis from 1,2,3,4,5-Benzopentathiepin and Active Methylene Compounds

16.4.6.1.2.2.3 Method 3: Synthesis from 1,2,3,4,5-Pentathiepins and Alkynes

16.4.6.1.2.3 Fragments S—C—C and S—C—C

16.4.6.1.2.3.1 Method 1: Thermolysis of 1,2,3-Thiadiazoles

16.4.6.1.2.3.2 Method 2: Synthesis from 4-(Alkylamino)-4-oxobutanoic Acids and Thionyl Chloride

16.4.6.1.3 By Formation of One S—C Bond

16.4.6.1.3.1 Fragment S—C—C—S—C—C

16.4.6.1.3.1.1 Method 1: Synthesis from 2-Chloro-1-phenylethane-1,1-dithiol and Sodium Sulfide

16.4.6.1.3.1.2 Method 2: Synthesis from 1,8-Diketones

16.4.6.2 Synthesis by Ring Transformation

16.4.6.2.1 By Ring Contraction

16.4.6.2.1.1 Method 1: Synthesis by Photolysis of Unsaturated 18-Membered Thia-Crown Ethers

16.4.6.2.1.2 Method 2: Synthesis by Pummerer Dehydration of 3,8-Dihydro-1,2,5,6-dithiadiazocine 1-Oxides

16.4.6.3 Aromatization-Type Reactions

16.4.6.3.1 By Elimination

16.4.6.3.1.1 Method 1: Synthesis from 2-Chloro- and 2,3-Dichloro-1,4-dithianes

16.4.6.3.1.2 Method 2: Synthesis from 1,4-Dithiane-2,5-diol

16.4.6.4 Synthesis by Substituent Modification

16.4.6.4.1 Substitution of Existing Substituents

16.4.6.4.1.1 Of Hydrogen

16.4.6.4.1.1.1 Method 1: Introduction of Alkyl and Carboxamide Groups by Radical Substitution

16.4.6.4.2 Rearrangement of Substituents

16.4.6.4.2.1 Method 1: Isomerization of 1,4-Dithiins via Ring-Opening–Ring-Closing Reactions

16.4.6.4.3 Modification of Substituents

16.4.6.4.3.1 Modification of Sulfur Substituents

16.4.6.4.3.1.1 Method 1: Ring Opening of Acenaphtho[1,2-b][1,3]dithiolo[4,5-e][1,4]dithiin-9-one with Potassium tert-Butoxide

16.4.6.4.3.1.2 Method 2: Synthesis of Tin Dithiolates from Ketones by Grignard Reaction

16.18 Product Class 18: Pyridopyridazines

16.18.7 Pyridopyridazines

S. Lou and J. Zhang

16.18.7 Pyridopyridazines

16.18.7.1 Pyrido[2,3-c]pyridazines

16.18.7.1.1 Synthesis by Ring-Closure Reactions

16.18.7.1.1.1 By Formation of One N—C and One C—C Bond

16.18.7.1.1.1.1 Method 1: Cyclization of 3-Aminopyridazine-4-carbonitrile with Malonates

16.18.7.1.1.2 By Formation of One N—N Bond

16.18.7.1.1.2.1 Method 1: Annulation of 3-(2-Nitrophenyl)quinolin-2-amine

16.18.7.2 Pyrido[2,3-d]pyridazines

16.18.7.2.1 Synthesis by Ring-Closure Reactions

16.18.7.2.1.1 By Formation of Two N—C Bonds

16.18.7.2.1.1.1 Method 1: Condensation of Hydrazine with a Dicarbonyl-Functionalized Piperidinone Scaffold

16.18.7.2.1.1.2 Method 2: Condensation of Hydrazine with 2-Formylquinoline-3-carboxylate

16.18.7.2.1.1.3 Method 3: Incorporating a (2-Formylpyridin-3-yl)copper Reagent in Pyrido[2,3-d]pyridazine Synthesis

16.18.7.2.1.1.4 Method 4: Suzuki Cross Coupling of Chloro(methoxy)pyridazin-3(2H)-ones

16.18.7.2.1.1.5 Method 5: Condensation of 5,6-Dicarbonyl-Functionalized Pyridinones with Hydrazine

16.18.7.2.1.2 By Formation of One N—C and One C—C Bond

16.18.7.2.1.2.1 Method 1: Condensation of Acetone with 5-Acetyl-4-amino-6-phenylpyridazin-3(2H)-one

16.18.7.2.2 Synthesis by Ring Transformation

16.18.7.2.2.1 By Ring Enlargement

16.18.7.2.2.1.1 Method 1: Condensation of Hydrazine with Pyridine-2,3-dicarboxylic Anhydride and 3-Benzoylpicolinic Acid

16.18.7.2.2.1.2 Method 2: Condensation of Hydrazine with Pyrrolo[3,4-c]pyridinone

16.18.7.3 Pyrido[3,2-c]pyridazines

16.18.7.3.1 Synthesis by Ring-Closure Reactions

16.18.7.3.1.1 By Formation of One N—N Bond

16.18.7.3.1.1.1 Method 1: Condensation and Reduction of 2-Amino-2′-nitrobiaryls

16.18.7.4 Pyrido[3,4-c]pyridazines

16.18.7.4.1 Synthesis by Ring-Closure Reactions

16.18.7.4.1.1 By Formation of One N—N and One N—C Bond

16.18.7.4.1.1.1 Method 1: Intramolecular Diazo Coupling of 4-Hetarylpyridin-3-amines

16.18.7.5 Pyrido[3,4-d]pyridazines

16.18.7.5.1 Synthesis by Ring Transformation

16.18.7.5.1.1 By Ring Enlargement

16.18.7.5.1.1.1 Method 1: Condensation of Hydrazine with 1H-Pyrrolo[3,4-c]pyridine-1,3(2H)-dione

16.18.7.5.1.1.2 Method 2: Ring Expansion of Pyrazolopyridines

16.18.7.5.1.1.3 Method 3: Insertion of Hydrazine into (Z)-3-Benzylidenefuro[3,4-c]pyridin-1(3H)-ones

16.18.7.6 Pyrido[4,3-c]pyridazines

16.18.7.6.1 Synthesis by Ring-Closure Reactions

16.18.7.6.1.1 By Formation of One N—C and One C—C Bond

16.18.7.6.1.1.1 Method 1: Fusion of an Aminouracil with a Chloropyridazinecarbonitrile or Pyridazines Having Vicinal Chloro and Carbonyl Groups

16.19 Product Class 19: Pyridopyrimidines

16.19.5 Pyridopyrimidines

Y.-J. Wu

16.19.5 Pyridopyrimidines

16.19.5.1 Pyrido[2,3-d]pyrimidines

16.19.5.1.1 By Formation of Three N—C Bonds and One C—C Bond

16.19.5.1.1.1 Method 1: Cyclization of Acrylates, Functionalized Nitriles, and Guanidines or Amidines

16.19.5.1.2 By Formation of One N—C and Two C—C Bonds

16.19.5.1.2.1 Method 1: Cyclization of 2-Heterosubstituted 6-Aminopyrimidin-4(3H)-ones, Aldehydes, and Active Methylene Compounds

16.19.5.1.3 By Formation of Two N—C Bonds

16.19.5.1.3.1 Method 1: Cyclization of 2-Nitrogen-Functionalized Nicotinamides

16.19.5.1.4 By Formation of One N—C and One C—C Bond

16.19.5.1.4.1 Method 1: Cyclization of Pyrimidin-4-amines with α,β-Unsaturated Carbonyl Compounds and Related Species

16.19.5.1.5 By Formation of One N—C Bond

16.19.5.1.5.1 Method 1: Dehydrative Cyclization of 2-Acetamidonicotinamides

16.19.5.1.5.2 Method 2: Cyclization of 5-(4-Aminopyrimidin-5-yl)-1H-imidazole-4-carbonitriles

16.19.5.1.6 By Formation of One C—C Bond

16.19.5.1.6.1 Method 1: Palladium-Catalyzed Intramolecular Arylation of 4-(2-Bromobenzylamino)pyrimidines

16.19.5.2 Pyrido[3,2-d]pyrimidines

16.19.5.2.1 By Formation of Three N—C Bonds

16.19.5.2.1.1 Method 1: Cycloamination of 3-Isocyanatopyridine-2-carboxylates

16.19.5.2.2 By Formation of One C—C Bond

16.19.5.2.2.1 Method 1: Palladium-Catalyzed Intramolecular Arylation of 5-(2-Halobenzylamino)pyrimidines

16.19.5.3 Pyrido[3,4-d]pyrimidines

16.19.5.3.1 By Formation of Two N—C Bonds

16.19.5.3.1.1 Method 1: Cyclization of 3-Nitrogen-Functionalized Pyridine-4-carboxylic Acids with Nitrogen-Containing Compounds

16.19.5.3.2 By Formation of One N—C and One C—C Bond

16.19.5.3.2.1 Method 1: Suzuki Coupling/Condensation of 5-Bromopyrimidine-4-carboxylates with (2-Aminophenyl)boronic Acids

16.19.5.4 Pyrido[4,3-d]pyrimidines

16.19.5.4.1 By Formation of Two N—C Bonds and One C—C Bond

16.19.5.4.1.1 Method 1: Cyclization of 1-Benzylpiperidin-4-one, Nitriles, and Trifluoromethanesulfonic Anhydride

16.19.5.4.2 By Formation of Two N—C Bonds

16.19.5.4.2.1 Method 1: Cyclization of 4-(Arylethynyl)pyrimidine-5-carbaldehydes with tert-Butylamine

16.19.5.4.2.2 Method 2: Cycloamination of N-(3-Acetylpyridin-4-yl)formimidates with Primary Amines

16.21 Product Class 21: Pteridines and Related Structures

16.21.4 Pteridines and Related Structures

T. Ishikawa

16.21.4 Pteridines and Related Structures

16.21.4.1 Synthesis by Ring-Closure Reactions

16.21.4.1.1 By Annulation to the Pyrimidine Ring

16.21.4.1.1.1 By Formation of Two N—C Bonds

16.21.4.1.1.1.1 Fragments N—C—C—N and C—C

16.21.4.1.1.1.1.1 Method 1: Synthesis from Pyrimidine-4,5-diamines and Diketones

16.21.4.1.1.1.1.2 Method 2: Synthesis from Pyrimidine-4,5-diamines and 1,2,3-Tricarbonyl Compounds

16.21.4.1.1.1.1.3 Method 3: Synthesis from Pyrimidine-4,5-diamines and Modified 1,2-Dicarbonyl Systems

16.21.4.1.1.1.1.4 Method 4: Synthesis from 5-Nitrosopyrimidin-4-amines and α,β-Unsaturated Acyl Halides

16.21.4.1.1.1.2 Fragments N—C—C and N—C—C

16.21.4.1.1.1.2.1 Method 1: From 4-Chloro-5-nitropyrimidines and α-Aminocarbonyl Compounds (Polonovski–Boon Reaction)

16.21.4.1.1.1.2.2 Method 2: From 4-Iodopyrimidin-5-amine and 1H-Pyrrole-2-carbaldehyde

16.21.4.1.2 By Annulation to the Pyrazine Ring

16.21.4.1.2.1 By Formation of Two N—C Bonds

16.21.4.1.2.1.1 Fragments N—C—C—C—N and C

16.21.4.1.2.1.1.1 Method 1: From 2,3-Disubstituted Pyrazines and One-Carbon Units

16.21.4.2 Synthesis by Ring Transformation

16.21.4.2.1 Method 1: Synthesis by Ring Contraction of Pyrimidoazepine Derivatives

16.21.4.3 Synthesis by Substituent Modification

16.21.4.3.1 Substitution of Existing Substituents

16.21.4.3.1.1 Substitution of Hydrogen

16.21.4.3.1.1.1 Method 1: N-Alkylation of Pteridinones or Their Derivatives

16.21.4.3.1.1.2 Method 2: Direct Introduction of Substituents by Nucleophilic Reactions

16.21.4.3.1.2 Substitution of Heteroatoms

16.21.4.3.1.2.1 Method 1: Substitution of Sulfur: Amination

16.21.4.3.1.2.3 Method 2: Substitution of Halogens: Alkylation

16.21.4.3.2 Modification of Substituents

16.21.4.3.2.1 Method 1: Hydrolysis

16.21.4.3.2.2 Method 2: Modification of Amine Substituents

16.21.4.3.2.3 Method 3: Oxidation of Alkylsulfanyl Substituents

16.21.4.3.3 Rearrangement of Substituents

16.21.4.3.3.1 Method 1: Rearrangement of Allyl Groups

16.22 Product Class 22: Other Diazinodiazines

16.22.6 Other Diazinodiazines

T. Ishikawa

16.22.6 Other Diazinodiazines

16.22.6.1 Pyridazinopyridazines

16.22.6.1.1 Addition Reactions

16.22.6.1.1.1 Method 1: Addition of Alkyl Groups

16.22.6.2 Pyrimidopyridazines

16.22.6.2.1 Synthesis by Ring-Closure Reactions

16.22.6.2.1.1 By Annulation to an Arene

16.22.6.2.1.1.1 By Formation of Two N—C Bonds

16.22.6.2.1.1.1.1 Method 1: From Substituted Pyridazines

16.22.6.2.1.1.1.2 Method 2: From Substituted Pyrimidines

16.22.6.2.1.1.2 By Formation of One N—C and One C—C Bond

16.22.6.2.1.1.2.1 Method 1: From 1,2-Dicarbonyl Compounds or α-Bromo Ketones

16.22.6.2.1.1.3 By Formation of One N—C Bond

16.22.6.2.1.1.3.1 Method 1: From 4,5-Disubstituted Pyrimidines

16.22.6.2.2 Synthesis by Substituent Modification

16.22.6.2.2.1 Substitution of Existing Substituents

16.22.6.2.2.1.1 Method 1: By Substitution of Chlorine

16.22.6.2.2.1.2 Method 2: By Substitution of Hydrogen

16.22.6.2.3 Addition Reactions

16.22.6.2.3.1 Method 1: Hydrogenation

16.22.6.3 Pyrimidopyrimidines

16.22.6.3.1 Synthesis by Ring-Closure Reactions

16.22.6.3.1.1 By Annulation to an Arene

16.22.6.3.1.1.1 By Formation of Two N—C Bonds

16.22.6.3.1.1.1.1 Method 1: From 2,4,5-Trisubstituted Pyrimidines

16.22.6.3.1.1.1.2 Method 2: From 4,5,6-Trisubstituted Pyrimidines

16.22.6.3.1.1.1.3 Method 3: From 2,4,5,6-Tetrasubstituted Pyrimidines

16.22.6.3.1.1.1.3.1 Variation 1: With a Guanidine or Thiourea

16.22.6.3.1.1.1.3.2 Variation 2: With a Thiouronium Chloride and an Amine

16.22.6.3.1.2 By Cycloaddition Reactions

16.22.6.3.1.2.1 By Formation of Two N—C Bonds

16.22.6.3.1.2.1.1 Method 1: By Diels–Alder Reaction

16.22.6.3.1.2.2 By Formation of One N—C and One C—C Bond

16.22.6.3.1.2.2.1 Method 1: By Diels–Alder Reaction

16.22.6.3.1.2.2.1.1 Variation 1: From Methyl 6-Methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

16.22.6.3.1.2.2.1.2 Variation 2: From 6-Amino-1,3-dimethylpyrimidine-2,4(1H,3H)-diones

16.22.6.3.2 Synthesis By Ring Transformation

16.22.6.3.2.1 By Ring Enlargement

16.22.6.3.2.1.1 Method 1: From Purine Skeletons

16.22.6.3.3 Synthesis by Substituent Modification

16.22.6.3.3.1 Modification of Existing Substituents

16.22.6.3.3.1.1 Method 1: By Substitution of Chlorine

16.22.6.3.3.1.2 Method 2: By Substitution of Sulfur-Containing Groups

Volume 17: Six-Membered Hetarenes with Two Unlike or More than Two Heteroatoms and Fully Unsaturated Larger-Ring Heterocycles

17.2 Product Class 2: Six-Membered Hetarenes with Three Heteroatoms

17.2.1.9 1,2,3-Triazines and Phosphorus Analogues

P. Aggarwal and M. W. P. Bebbington

17.2.1.9 1,2,3-Triazines and Phosphorus Analogues

17.2.1.9.1 Monocyclic 1,2,3-Triazines

17.2.1.9.1.1 Aromatization

17.2.1.9.1.1.1 Method 1: Dehydrogenation and Oxidation of 2,5-Dihydro-1,2,3-triazines

17.2.1.9.1.2 Synthesis by Substituent Modification

17.2.1.9.1.2.1 Addition Reactions

17.2.1.9.1.2.1.1 Method 1: Protonation of 1,2,3-Triazines by Tetrafluoroboric Acid

17.2.1.9.1.2.1.2 Method 2: N-Acylation, N-Alkylation, and N-Arylation

17.2.1.9.1.2.2 Modification of Substituents

17.2.1.9.1.2.2.1 Method 1: Dipolar Cycloaddition with Dicyano(1,2,3-triazin-2-ium-2-yl)methanides

17.2.1.9.1.2.2.2 Method 2: Dipolar Cycloaddition with 2-Ethyl-1,2,3-triazin-2-ium Salts

17.2.1.9.1.3 Applications of Monocyclic 1,2,3-Triazines in Organic Synthesis

17.2.1.9.1.3.1 Method 1: Synthesis of 2,5-Dihydro-1,2,3-triazines

17.2.1.9.2 Annulated 1,2,3-Triazines

17.2.1.9.2.1 Synthesis by Ring-Closure Reactions

17.2.1.9.2.1.1 By Annulation to a Heterocycle or Carbocycle

17.2.1.9.2.1.1.1 By Formation of Two N—N Bonds

17.2.1.9.2.1.1.1.1 Method 1: Reaction of a 2-(4,5-Dihydro-1H-imidazol-2-yl)thieno[2,3-b]pyridin-3-amine with Nitrous Acid

17.2.1.9.2.1.1.1.2 Method 2: Reaction of 2-Amino-1H-pyrrole-3,4-dicarboxamides with Nitrous Acid

17.2.1.9.2.1.1.1.3 Method 3: Reaction of Amino-Substituted Pyridine- and Pyridazinecarboxamides with Nitrous Acid

17.2.1.9.2.1.1.1.4 Method 4: Reaction of Amino-Substituted Hetarenecarbonitriles with Nitrous Acid and Hydrochloric Acid

17.2.1.9.2.1.1.1.5 Method 5: Diazotization of (Aminohetaryl)azoles

17.2.1.9.2.1.1.1.6 Method 6: Diazotization of 3,4-Diaminothieno[2,3-b]thiophene-2,5-dicarboxamide

17.2.1.9.2.1.1.2 By Formation of One N—C Bond

17.2.1.9.2.1.1.2.1 Method 1: Cyclization of 2-(Triaz-1-enyl)benzonitriles

17.2.1.9.2.1.2 By Annulation to the 1,2,3-Triazine Ring

17.2.1.9.2.1.2.1 By Formation of One C—C Bond

17.2.1.9.2.1.2.1.1 Method 1: Condensation Reactions of Annulated 4-Hydrazino-1,2,3-triazines

17.2.1.9.2.1.2.1.2 Method 2: Condensation Reactions of 4-Chloro-1,2,3-triazines

17.2.1.9.2.2 Synthesis by Substituent Modification

17.2.1.9.2.2.1 Substitution of Existing Substituents

17.2.1.9.2.2.1.1 Of Hydrogen

17.2.1.9.2.2.1.1.1 Method 1: N-Alkylation and N-Arylation

17.2.1.9.2.2.1.2 Of Heteroatoms

17.2.1.9.2.2.1.2.1 Method 1: Substitution of a 4-Chloro-Substitutent with Sulfur-Containing Groups

17.2.1.9.2.2.1.2.2 Method 2: Substitution of a 4-Chloro-Substitutent with Amino or Hydrazino Groups

17.2.1.9.2.2.1.2.3 Method 3: Substitution of a 4-Chloro-Substitutent with Sodium Azide

17.2.1.9.2.2.1.2.4 Method 4: Substitution of a 4-Hydroxy Group by a Halogen

17.2.1.9.2.2.1.2.5 Method 5: Substitution of Amino, 4-Hydrazino, and 4-(1H-1,2,4-Triazol-1-yl) Groups

17.2.1.9.2.2.2 Modification of Substituents

17.2.1.9.2.2.2.1 Method 1: Modification of Nitrogen Functionality

17.2.2.3 1,2,4-Triazines

P. Aggarwal and M. W. P. Bebbington

17.2.2.3 1,2,4-Triazines

17.2.2.3.1 Monocyclic 1,2,4-Triazines

17.2.2.3.1.1 Synthesis by Ring-Closure Reactions

17.2.2.3.1.1.1 By Formation of Three N—C Bonds

17.2.2.3.1.1.1.1 Fragments N—N—C, C—C, and N

17.2.2.3.1.1.1.1.1 Method 1: Microwave-Assisted Reaction of α-Diazo-β-oxo Esters with Hydrazides

17.2.2.3.1.1.1.1.2 Method 2: Microwave-Assisted Condensation of 1,2-Dicarbonyl Compounds, Hydrazides, and Ammonium Acetate

17.2.2.3.1.1.1.1.3 Method 3: Zirconium-Catalyzed Condensation of Benzil with Hydrazides

17.2.2.3.1.1.1.2 Fragments N—N, C—C, C—N

17.2.2.3.1.1.1.2.1 Method 1: One-Pot Condensation of Amides, 1,2-Diketones, and Hydrazine

17.2.2.3.1.1.2 By Formation of Two N—C Bonds

17.2.2.3.1.1.2.1 Fragments N—N—C—N and C—C

17.2.2.3.1.1.2.1.1 Method 1: Reaction of 1,2-Dicarbonyl Compounds with Amidrazones

17.2.2.3.1.1.2.1.2 Method 2: Reaction of 1,2-Dicarbonyl Compounds with Semicarbazides, Thiosemicarbazides, or Selenosemicarbazides

17.2.2.3.1.1.2.1.3 Method 3: Cyclization of Hydrazonoimidazolidines with α-Oxo Esters

17.2.2.3.1.1.2.1.4 Method 4: Reaction of Aminoguanidines with α,α-Dihalo Ketones

17.2.2.3.1.1.2.1.5 Method 5: Condensation of Thiosemicarbazide with Dialkyl Acetylenedicarboxylates

17.2.2.3.1.1.2.1.6 Method 6: Reaction of α-Functionalized Acetonitriles with 1H-Tetrazol-5-amine

17.2.2.3.1.1.2.2 Fragments N—C—C—N—N and C

17.2.2.3.1.1.2.2.1 Method 1: Condensation of Aryl(hydrazono)acetaldehyde Oximes with Pyridine-2,6-dicarbaldehyde

17.2.2.3.1.1.2.2.2 Method 2: Condensation of Aryl(hydrazono)acetaldehyde Oximes with Pyridinecarbaldehydes

17.2.2.3.1.1.2.2.3 Method 3: Condensation of Aryl(hydrazono)acetaldehyde Oximes with Quinoline-2-carbaldehydes

17.2.2.3.1.1.3 By Formation of One N—C Bond

17.2.2.3.1.1.3.1 Fragment C—C—N—N—C—N

17.2.2.3.1.1.3.1.1 Method 1: Cyclization of Silyl-Substituted Thiosemicarbazone Acetic Acid Esters

17.2.2.3.1.1.3.2 Fragment C—N—C—C—N—N

17.2.2.3.1.1.3.2.1 Method 1: Cyclization of α,β-Unsaturated α-Amido Hydrazides

17.2.2.3.1.2 Annulation by the Formation of a Second Heterocyclic Ring

17.2.2.3.1.2.1 Method 1: Cyclization of Hydrazides with 1,2,4-Triazin-3(2H)-ones

17.2.2.3.1.2.2 Method 2: Cyclization of 6-Benzyl-5-hydrazino-1,2,4-triazin-3(2H)-one with Amidinium Salts

17.2.2.3.1.2.3 Method 3: Sonagashira Coupling–Cyclization of 6-Chloro-1,2,4-triazine-3,5-diamines

17.2.2.3.1.2.4 Method 4: Cyclization of 6-Acetamido-1,2,4-triazine-5-carboxylates

17.2.2.3.1.2.5 Method 5: Cyclization of 3-Amino-1,2,4-triazin-5(4H)-ones with Glyoxal

17.2.2.3.1.2.6 Method 6: Cyclization of 5-Azido-2,3-dimethyl-2H-pyrazolo[4,3-e][1,2,4]triazine

17.2.2.3.1.2.7 Method 7: Cyclization of 5-[Hydrazono(3,4,5-trimethoxyphenyl)methyl]-1,2,4-triazin-6(1H)-ones

17.2.2.3.1.3 Aromatization

17.2.2.3.1.3.1 Method 1: Dehydration of Dihydrotriazines

17.2.2.3.1.3.2 Method 2: N-Deacylation and Oxidation of Tetrahydro-1,2,4-triazine

17.2.2.3.1.4 Synthesis by Substituent Modification

17.2.2.3.1.4.1 Substitution of Existing Substituents

17.2.2.3.1.4.1.1 Of Hydrogen

17.2.2.3.1.4.1.1.1 Method 1: Reaction of 1,2,4-Triazine 4-Oxides with Terminal Alkynes

17.2.2.3.1.4.1.2 Of Carbon Functionalities

17.2.2.3.1.4.1.2.1 Method 1: Reaction of 1,2,4-Triazine-5-carbonitriles with Nucleophiles

17.2.2.3.1.4.1.3 Of Heteroatoms

17.2.2.3.1.4.1.3.1 Method 1: Reaction of Chloro-Substituted 1,2,4-Triazines with Amines

17.2.2.3.1.4.1.3.2 Method 2: Reaction of Methylsulfonyl-Substituted 1,2,4-Triazines with Alkynyllithium Reagents

17.2.2.3.1.4.1.3.3 Method 3: Reaction of Methylsulfanyl-Substituted 1,2,4-Triazines with Amines

17.2.2.3.1.4.1.3.4 Method 4: Deamination with Preyssler’s Anion

17.2.2.3.1.4.2 Addition Reactions

17.2.2.3.1.4.2.1 Method 1: Nucleophilic Addition of Cyanide to 1,2,4-Triazine 4-Oxides

17.2.2.3.1.4.2.2 Method 2: Nucleophilic Addition of Indoles to 1,2,4-Triazine 4-Oxides

17.2.2.3.1.4.2.3 Method 3: Nucleophilic Addition of Carboranes to 1,2,4-Triazine 4-Oxides

17.2.2.3.1.4.3 Modification of Substituents

17.2.2.3.1.4.3.1 Method 1: Methylation of 3-Thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-ones

17.2.2.3.1.4.3.2 Method 2: N-Acylation of Ethyl 6-Amino-1,2,4-triazine-5-carboxylate

17.2.2.3.1.4.3.3 Method 3: Displacement of an α-Hydroxy Group with a Halide

17.2.2.3.1.4.3.4 Method 4: α-Halogen Exchange

17.2.2.3.1.4.3.5 Method 5: Displacement of an α-Fluoride with Amines

17.2.2.3.1.4.3.6 Method 6: Displacement of an α-Chloride with Thiols

17.2.2.3.1.4.3.7 Method 7: Displacement of an α-Chloride with Amines

17.2.2.3.1.4.3.8 Method 8: Displacement of an α-Chloride by Wittig Reaction

17.2.2.3.1.4.3.9 Method 9: Ring Cleavage of Tetrazolo[1,5-b][1,2,4]triazin-7-amines

17.2.2.3.1.4.3.10 Method 10: Palladium-Catalyzed Arylation of 1,2,4-Triazin-3-amine

17.2.2.3.2 1,2,4-Benzotriazines and Related Compounds

17.2.2.3.2.1 Synthesis by Ring-Closure Reactions

17.2.2.3.2.1.1 By Formation of One N—N and One N—C Bond

17.2.2.3.2.1.1.1 Fragments N—C—C—N and N—C

17.2.2.3.2.1.1.1.1 Method 1: Reaction of 2-Nitroanilines with Cyanamide

17.2.2.3.2.1.1.2 Fragments N—C—N and N—C—C

17.2.2.3.2.1.1.2.1 Method 1: Reaction of 1-Halo-2-nitrobenzenes with Guanidine Hydrochloride

17.2.2.3.2.2 Synthesis by Ring Transformation

17.2.2.3.2.2.1 Method 1: Isomerization of Angular Triazinium Salts

17.2.2.3.2.3 Synthesis by Substituent Modification

17.2.2.3.2.3.1 Addition Reactions

17.2.2.3.2.3.1.1 Method 1: Oxidation of 1,2,4-Benzotriazin-3-amine 1-Oxides

17.2.3.6 1,3,5-Triazines and Phosphorus Analogues

P. Aggarwal and M. W. P. Bebbington

17.2.3.6 1,3,5-Triazines and Phosphorus Analogues

17.2.3.6.1 1,3,5-Triazines

17.2.3.6.1.1 Synthesis by Ring-Closure Reactions

17.2.3.6.1.1.1 By Formation of Three N—C Bonds

17.2.3.6.1.1.1.1 Fragments N—C, N—C, and N—C

17.2.3.6.1.1.1.1.1 Method 1: Trimerization of Dialkylcyanamides or Nitriles

17.2.3.6.1.1.1.1.2 Method 2: Trimerization of Imidates

17.2.3.6.1.1.1.1.3 Method 3: Reaction of Carbodiimides with Nitrilium Salts

17.2.3.6.1.1.2 By Formation of Two N—C Bonds

17.2.3.6.1.1.2.1 Fragments N—C—N—C and N—C

17.2.3.6.1.1.2.1.1 Method 1: Reaction of Guanidine-1-carbonitrile with Nitriles

17.2.3.6.1.1.2.2 Fragments N—C—N and C—N—C

17.2.3.6.1.1.2.2.1 Method 1: Reaction of Isothiocyanates with Amidines or Guanidines

17.2.3.6.1.1.2.2.2 Method 2: Reaction of Isothiocyanates with Sodium Hydrogen Cyanamide

17.2.3.6.1.1.2.2.3 Method 3: Reaction of N-Functionalized Imidoyl Chlorides with Amidine Derivatives

17.2.3.6.1.1.2.2.4 Method 4: Reaction of N-(2,2-Dichlorovinyl)benzamides with Amidines

17.2.3.6.1.1.2.2.5 Method 5: Reaction of 4-Oxo-1,3-benzoxazinium Perchlorates with Guanidines

17.2.3.6.1.1.2.2.6 Method 6: Reaction of Amidinium Salts with Pyrazolamines or 1,2,4-Triazolamines

17.2.3.6.1.1.2.3 Fragments N—C—N—C—N and C

17.2.3.6.1.1.2.3.1 Method 1: Reaction of Biguanides with Carboxylic Acid Derivatives

17.2.3.6.1.1.2.3.2 Method 2: Reaction of Zinc(II) Bis[bis(methoxyimido)amide] with Carboxylic Acid Derivatives

17.2.3.6.1.2 Synthesis by Substituent Modification

17.2.3.6.1.2.1 Substitution of Existing Substituents

17.2.3.6.1.2.1.1 Of Hydrogen

17.2.3.6.1.2.1.1.1 Method 1: Amination

17.2.3.6.1.2.1.2 Of Carbon Functionalities

17.2.3.6.1.2.1.2.1 Method 1: Substitution of Trinitromethyl Groups

17.2.3.6.1.2.1.2.2 Method 2: Substitution of Cyano Groups

17.2.3.6.1.2.1.2.3 Method 3: Substitution of Bis(tert-Butoxycarbonyl)(nitro)methyl Groups

17.2.3.6.1.2.1.3 Of Halogens by Carbon Functionalities

17.2.3.6.1.2.1.3.1 Method 1: Reaction with Grignard Reagents

17.2.3.6.1.2.1.3.2 Method 2: Reaction with Boronic Acids (Suzuki Coupling)

17.2.3.6.1.2.1.3.3 Method 3: Reaction with Organotin Reagents

17.2.3.6.1.2.1.3.4 Method 4: Reaction with Arynes

17.2.3.6.1.2.1.3.5 Method 5: Reaction with Arylzinc Chlorides (Negishi Coupling)

17.2.3.6.1.2.1.3.6 Method 6: Nickel-Catalyzed Ullmann Homocoupling Reactions

17.2.3.6.1.2.1.3.7 Method 7: Cobalt-Catalyzed Arylation or Benzylation Reactions

17.2.3.6.1.2.1.3.8 Method 8: Sonagashira Reactions

17.2.3.6.1.2.1.3.9 Method 9: Cross-Coupling Reactions with Organoaluminum Compounds

17.2.3.6.1.2.1.4 Of Halogens by Oxygen Functionalities

17.2.3.6.1.2.1.4.1 Method 1: Exchange of Chlorine in 2,4,6-Trichloro-1,3,5-triazine

17.2.3.6.1.2.1.4.2 Method 2: Exchange of Chlorine in Chloro-Substituted 1,3,5-Triazines

17.2.3.6.1.2.1.5 Of Halogens by Sulfur Functionalities

17.2.3.6.1.2.1.5.1 Method 1: Exchange of Chlorine for an Alkylsulfanyl Group

17.2.3.6.1.2.1.5.2 Method 2: Exchange of Chlorine for an Arylsulfanyl Group

17.2.3.6.1.2.1.6 Substitution of Halogens by Selenium or Tellurium Functionalities

17.2.3.6.1.2.1.6.1 Method 1: Exchange of Chlorine with Chalcogenide Nucleophiles

17.2.3.6.1.2.1.7 Of Halogens by Nitrogen Functionalities

17.2.3.6.1.2.1.7.1 Method 1: Reaction of 2,4,6-Trichloro-1,3,5-triazine with Amines (Monosubstitution)

17.2.3.6.1.2.1.7.2 Method 2: Reaction of 2,4,6-Trichloro-1,3,5-triazine with Amines (Trisubstitution)

17.2.3.6.1.2.1.7.3 Method 3: Reaction of 2,4-Dichloro-1,3,5-triazines with Amines

17.2.3.6.1.2.1.7.4 Method 4: Reaction of 2-Chloro-1,3,5-triazines with Amines

17.2.3.6.1.2.1.7.5 Method 5: Reaction of 2-Chloro-1,3,5-triazines with Ureas or Thioureas

17.2.3.6.1.2.1.8 Generation of 1,3,5-Triazine Libraries by Substitution of Chlorine by Oxygen or Nitrogen Functionalities

17.2.3.6.1.2.1.8.1 Method 1: Parallel Synthesis on Solid Supports

17.2.3.6.1.2.1.9 Of Sulfur Functionalities

17.2.3.6.1.2.1.9.1 Method 1: Substitution of Sulfonyl Groups

17.2.3.6.1.2.1.9.2 Method 2: Cross Coupling of Sulfanyl-Substituted 1,3,5-Triazines with Functionalized Organozinc Reagents

17.2.3.6.1.2.1.9.3 Method 3: Reductive Rearrangement of 2-(Triazinylsulfanyl)benzamides

17.2.3.6.1.2.2 Rearrangement of Substituents

17.2.3.6.1.2.2.1 Method 1: Smiles Rearrangement

17.2.3.6.1.2.2.2 Method 2: Thermal Isomerization of 2,4,6-Trialkoxy-1,3,5-triazines

17.2.3.6.1.2.3 Modification of Substituents

17.2.3.6.1.2.3.1 Method 1: S-Oxidation

17.2.3.6.1.2.3.2 Method 2: Modification at the α-Carbon

17.2.3.6.1.2.3.2.1 Variation 1: Conversion of Trinitromethyl Groups into Nitriles

17.2.3.6.1.2.3.2.2 Variation 2: Conversion of Trinitromethyl Groups into Nitrile Oxides and Subsequent Heterocycle Formation

17.2.3.6.1.2.3.2.3 Variation 3: Conversion of Dinitromethyl Groups into Oxadiazole 2-Oxides

17.2.3.6.1.2.3.2.4 Variation 4: Conversion of Alkynyltriazines into Triazoles Using Click Chemistry

17.2.3.6.1.2.3.3 Method 3: Reaction of Nitrogen Substituents

17.2.3.6.1.2.3.3.1 Variation 1: N-Heterocycle Formation

17.2.3.6.1.2.3.3.2 Variation 2: N-Alkylation

17.2.3.6.1.2.3.3.3 Variation 3: Debenzylation

17.2.3.6.1.2.3.3.4 Variation 4: Thiourea and Thiazole Formation

Volume 34: Fluorine

34.1 Product Class 1: Fluoroalkanes

34.1.1.7 Synthesis by Substitution of Hydrogen

G. Sandford

34.1.1.7 Synthesis by Substitution of Hydrogen

34.1.1.7.1 Method 1: Direct Fluorination with Elemental Fluorine

34.1.1.7.2 Method 2: Reaction with Selectfluor

Author Index

Abbreviations

4.4.25.11 Acylsilanes (Update 2012)

M. Nahm Garrett and J. S. Johnson

General Introduction

Acylsilanes continue to evolve as interesting and viable reagents for organic synthesis. This chapter serves to highlight reports of both the synthesis of acylsilanes and their applications since 2000.

Several methods reported for the synthesis of acylsilanes in Science of Synthesis (Section 4.4.25) are staple protocols still employed today. Synthetic methods described herein are divided according to five target product subtypes: simple acylsilanes, bis(acylsilanes), α-oxo acylsilanes, α,β-unsaturated acylsilanes, and α-amino acylsilanes. The largest of those sections, simple acylsilanes, is further divided into these main strategies: hydrolysis of acetals, oxidation of organocuprates, and acyl substitution of carboxylic amides.

A significant amount of research on the reactivity of acylsilanes has been carried out since 2000. Applications highlighted in this section are covered in turn with respect to four general types of acylsilanes: simple acylsilanes, bis(acylsilanes), α-oxo acylsilanes, and α,β-unsaturated acylsilanes. The section on reactions of simple acylsilanes is further divided into the following categories: nucleophilic addition, nucleophilic addition with Brook rearrangement, acylsilanes as acyl anion precursors, enolate and enol ether reactions, and photochemistry, with a section of miscellaneous additional methods that fall outside these five subdivisions.

A defining characteristic of many acylsilane-based transformations is a reaction sequence involving nucleophilic addition to the carbonyl carbon atom followed by 1,2-Brook rearrangement. This two-step progression enables the application of acylsilanes as (a) dipolar linchpin reagents for coupling nucleophiles and electrophiles at the same carbon atom (or one connected vinylogously), or (b) as acyl anion equivalents. The structures of the acylsilane and the nucleophilic species are important determinants as to which type of manifold will be dominant.

4.4.25.11.1 Synthesis of Acylsilanes

4.4.25.11.1.1 Method 1: Synthesis of Simple Acylsilanes

4.4.25.11.1.1.1 Variation 1: Hydrolysis of Acetals

One of the most general and widely used methods for the synthesis of acylsilanes remains the hydrolysis of 2-silyl-1,3-dithianes, which was initially investigated in the 1960s (▶ Scheme 1).[1,2] Several efforts have been reported that alter the hydrolysis conditions to avoid the use of toxic mercury(II) chloride.

▶ Scheme 1 Preparation and Hydrolysis of 2-Silyl-1,3-dithianes[1,2]

One approach is the oxidative hydrolysis mediated by N-bromosuccinimide in an acetone/water or acetonitrile/water mixture.[3] When compared to the mercury(II) chloride hydrolysis, N-bromosuccinimide often leads to shorter reaction times of 30–40 minutes as opposed to 12 hours. Some 2-aryl-2-silyl-1,3-dithiane substrates initially posed a problem under N-bromosuccinimide conditions because of overoxidation to the carboxylic acid. The formation of this side product can be minimized by the addition of a base such as triethylamine, barium hydroxide, or imidazole. Conducting the reaction at −23 °C instead of 0 °C also reduces carboxylic acid formation. In ▶ Scheme 2 the yields of some acyltrimethylsilanes 1 are compared using mercury(II) chloride versus N-bromosuccinimide hydrolysis,[3] demonstrating greater yields for the latter in most cases.

▶ Scheme 2 Hydrolysis of 2-Silyl-1,3-dithianes[3]

Ar

1

Conditions

Yield (%)

Ref

Ph

HgCl

2

70

[

3

]

Ph

NBS, acetone, −23 °C

74

[

3

]

2-MeOC

6

H

4

HgCl

2

65

[

3

]

2-MeOC

6

H

4

NBS, Et

3

N, acetone, 0 °C

90

[

3

]

4-ClC

6

H

4

HgCl

2

25

[

3

]

4-ClC

6

H

4

NBS, Ba(OH)

2

, MeCN, −23 °C

40

[

3

]

[Bis(trifluoroacetoxy)iodo]benzene has been used in oxidative hydrolysis to synthesize acyl(allyl)- and acyl(vinyl)silanes 2 (▶ Scheme 3).[4,5]

▶ Scheme 3 Synthesis of Acyl(allyl)- and Acyl(vinyl)silanes[4,5]

R

1

R

2

Yield (%)

Ref

Ph

CH

2

CH=CH

2

62

[

4

]

Cy

CH

2

CH=CH

2

88

[

4

]

(CH

2

)

2

Ph

CH

2

CH=CH

2

60

[

4

]

Bn

CH

2

CH=CH

2

75

[

4

]

Ph

CH=CH

2

60

[

4

]

Acylsilanes 1; General Procedure Using N-Bromosuccinimide:[3]

The 2-(trimethylsilyl)-1,3-dithiane was slowly added to a stirred mixture of NBS (4–6 molar equiv) in 80% aq acetone or MeCN (~25 mL) at 0 or −23 °C (see ▶ Scheme 2). During the addition of the dithiane, the pH was maintained at nearly neutral by simultaneous addition of base [Et3N (4–6 equiv) or Ba(OH)2 (2–3 equiv)]. After complete addition of the dithiane, stirring of the mixture was maintained for an additional 20–30 min at 0 °C. The cold bath was removed, Na2S soln (~25 mL) was rapidly added, and the product was extracted with EtOAc (3 × 25 mL). The combined organic layers were washed with H2O (40 mL) and dried (MgSO4), and the solvent was removed under reduced pressure. The product was purified by filtration through a short column (silica gel, hexane/EtOAc 9:1); yield: 40–90%.

Acyl(allyl)- and Acyl(vinyl)silanes 2; General Procedure:[4]

To a soln of a 2-alkyl- or 2-phenyl-1,3-dithiane (0.67 mmol) in MeOH (3 mL) were successively added NaHCO3 (2.68 mmol, 4 equiv) and [bis(trifluoroacetoxy)iodo]benzene (1.34 mmol, 2 equiv). The mixture was stirred at rt until the disappearance of the starting material (45–75 min) and then poured into a mixture of 1 M HCl (15 mL) and Et2O (15 mL). The organic layer was separated and the aqueous layer was extracted with Et2O (3 × 5 mL). The combined organic phases were dried (MgSO4) and filtered, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether/EtOAc 99:1); yield: 60–88%.

4.4.25.11.1.1.2 Variation 2: Oxidation of Organocuprates

1,1-Disilylalkylcopper compounds are oxidized by atmospheric oxygen to furnish acylsilanes in high yields.[6] The 1,1-disilylalkylcopper compounds have been synthesized by two methods. The first preparation involves treatment of a 1,1-disilylethene 3 with an organolithium compound to give 1,1-disilylalkyllithium 4, which upon transmetalation with a copper salt gives the 1,1-disilylalkylcopper reagent 5 (▶ Scheme 4).[6] One limitation of this preparation is that only alkyllithium reagents can react with 1,1-disilylethene 3. The second preparation involves reaction of butyllithium with dichlorobis(methyldiphenylsilyl)methane (6) to yield disilylalkyllithium 7, followed by addition of a Grignard reagent in the presence of a copper salt to afford 1,1-disilylalkylcopper 8 (▶ Scheme 5).[6]The second preparation enables incorporation of a variety of alkyl groups since various primary or secondary Grignard reagents can be employed.

▶ Scheme 4 Preparation of a 1,1-Disilylalkylcopper Compound from a 1,1-Disilylethene[6]

▶ Scheme 5 Preparation of 1,1-Disilylalkylcopper Compounds from Dichlorobis(methyldiphenylsilyl)methane[6]

For the oxidation step, after addition of an ammonium chloride additive to the 1,1-disilylalkylcopper compounds 8, the mixture is exposed to air with stirring for 30 minutes; the resulting blue aqueous layer is suggestive of copper(II). After purification, the desired acylsilanes 9 are obtained in high yields from dichlorobis(methyldiphenylsilyl)methane (6) (▶ Scheme 6).[6] Aroylsilanes have also been synthesized via this method with the addition of 4 equivalents of pyridine during the oxidation step to yield the corresponding benzoylsilane (84%), as well as larger π-conjugated systems such as those containing 2-naphthoyl (82%) and 9-phenanthroyl (73%) groups.[7] These reaction conditions are also tolerant of less nucleophilic arylmagnesiums such as 4-fluorophenyl- (72%) and pentafluorophenylmagnesium bromide (76%).

▶ Scheme 6 Preparation of Acylsilanes via Aerobic Oxidation of 1,1-Disilylalkylcopper Compounds[6,7]

R

1

X

Yield (%)

Ref

Et

Br

75

[

6

,

7

]

Bu

Br

81

[

6

,

7

]

(CH

2

)

3

Ph

Br

75

[

6

,

7

]

cyclopentyl

Br

84

[

6

,

7

]

iPr

Br

88

[

6

,

7

]

CH

2

CH=CH

2

Cl

72

[

6

]

CH

2

SiMe

3

Cl

67

[

6

]

The preceding protocol is limited to silyl substituents with at least one aryl group, but has been amended to yield acyltrialkylsilanes by employing a boryl group in place of one of the silyl groups. The 1-boryl-1-silylalkylcopper reagents are considered more effective in their oxidation to acylsilanes because the boron atom provides a vacant orbital and smaller atomic radius, lending itself to more efficient migration.[8] (Boryldichloromethyl)silanes 13 are synthesized in excellent yields by the treatment of the corresponding (dichloromethyl)silanes 10 with butyllithium to give [dichloro(lithio)methyl]silanes 11, followed by 2-methoxy-1,3,2-dioxaborolane 12 (▶ Scheme 7).[8]

▶ Scheme 7 Synthesis of (Boryldichloromethyl)silanes[8]

R

1

R

2

Yield (%)

Ref

Me

Ph

92

[

8

]

Ph

Me

85

[

8

]

t

-Bu

Me

78

[

8

]

A solution of butyllithium in tetrahydrofuran is added to the (boryldichloromethyl)silane 13 producing a yellow solution, which is subsequently treated with 1.1 equivalents of a copper salt and Grignard reagent to yield the 1-boryl-1-silylalkylcopper compounds 14. The previous oxidation conditions for the 1,1-disilylalkylcopper reagents with air and aqueous ammonium chloride often lead to the hydrolysis of 14; however, aerobic oxidation of 14 under aprotic conditions in the presence of 4 equivalents of pyridine affords the desired acylsilanes 15 in good yields from a one-pot process beginning with (boryldichloromethyl)silanes 13 (▶ Scheme 8).[8]

▶ Scheme 8 Synthesis of Acylsilanes via Aerobic Oxidation of 1-Boryl-1-silylalkylcoppers[8]

R

1

R

2

R

3

Yield (%)

Ref

Me

Ph

Ph

86

[

8

]

Ph

Me

Bu

81

[

8

]

Ph

Me

Ph

76

[

8

]

t

-Bu

Me

Bu

76

[

8

]

t

-Bu

Me

Ph

65

[

8

]

CAUTION:

Cyanide salts can be absorbed through the skin and are extremely toxic.

A 1.6 M soln of BuLi in hexane (0.31 mL, 0.5 mmol) was added to a THF soln of dichlorobis(methyldiphenylsilyl)methane (6; 239 mg, 0.5 mmol) at −78 °C. After the mixture was stirred for 20 min, a soln of iPrMgBr in THF (0.6 mmol) and 1.0 M CuCN•2LiCl in THF (0.6 mmol) were introduced and the resulting mixture was stirred for 1 h at 0 °C. Hexane (5 mL) and aq NH4Cl (10 mL) were added, and the mixture was exposed to air with stirring for 0.5 h. Extractive workup and purification afforded the product; yield: 118 mg (88%).

CAUTION:

Cyanide salts can be absorbed through the skin and are extremely toxic.

4.4.25.11.1.1.3 Variation 3: Nucleophilic Substitution of Morpholine Amides

Acylsilanes may be directly accessed from silyl nucleophiles and electrophilic carboxylic acid derivatives.[9,10] The addition of silyl nucleophiles to amides was reported in the mid 1990s,[11] and the scope was expanded upon in 2004. The direct addition of dimethyl(phenyl)silyllithium to morpholine amides is an economical approach that avoids overaddition and does not rely on stoichiometric quantities of a transition metal.[12] This protocol employs the addition of 1.5 equivalents of dimethyl(phenyl)silyllithium to the corresponding morpholine amide 16 followed by addition of aqueous ammonium chloride to yield the desired acylsilane 17 in high yield (60–82%) (▶ Scheme 9).[12,13]

▶ Scheme 9 Synthesis of Acylsilanes from Alkyl Morpholine Amides[12,13]

R

1

Yield (%)

Ref

Me

76

[

12

]

Et

75

[

12

]

iPr

60

[

12

]

t

-Bu

65

[

12

]

Cy

65

[

12

]

(CH

2

)

2

Ph

80

[

12

]

(CH

2

)

6

Me

81

[

12

]

(CH

2

)

2

CH=CH

2

72

[

12

]

cyclopropyl

82

[

12

]

This nucleophilic acyl substitution works well for branched and linear alkyl acylsilanes with the dimethyl(phenyl)silyl substituent; however, this protocol has not extended well to either aroylsilanes or alternative substituents on the silyl group. It does allow for the synthesis of alkyl or silyl O-protected 4-hydroxy-1-morpholinobutanone substrates to afford acylsilanes in moderate to high yields.[12]

Acylsilanes 17; General Procedure:[12]

The morpholine amide 16 (2 mmol) was added to a flame-dried, 50-mL round-bottomed flask under dry N2. THF (3 mL) was added and the soln was then cooled to −78 °C. A 1.0 M soln of dimethyl(phenyl)silyllithium in THF (3 mL) was added dropwise via syringe, and the mixture was stirred for 1.5 h. The reaction was quenched at −78 °C (very important to prevent decomposition) by addition of sat. aq NH4Cl (4 mL). The resulting heterogeneous mixture was allowed to warm to rt and then stirred for an additional 30 min. The mixture was then partitioned between H2O (5 mL) and Et2O (5 mL). The phases were separated and the aqueous phase was extracted with Et2O (2 × 5 mL). The combined organic extracts were washed with H2O (2 × 20 mL) and brine (20 mL), dried (MgSO4), and filtered, and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography (silica gel) to yield the pure acylsilane; yield: 60–82%.

4.4.25.11.1.1.4 Variation 4: Additional Synthetic Methods

The [1,4]-Wittig rearrangement has not been explored to the extent that the [1,2]- and [2,3]-Wittig rearrangements have. For substrates that can undergo a [1,4]-Wittig rearrangement, the [1,2]-rearrangement is often a competitive pathway.[14–17] In an earlier study, [1-(benzyloxy)allyl]silane 18 reacted with methyllithium to give a mixture of the acylsilane arising from a [1,4]-Wittig rearrangement, and a second compound derived from [1,2]-Wittig rearrangement. The acylsilane from the [1,4]-Wittig rearrangement is favored in a 3:1 ratio when the reaction is run at room temperature.[18] This initial result has been optimized using sec-butyllithium (1.5 equivalents) in tetrahydrofuran at −78 °C to give the desired acylsilane exclusively after 30 minutes.[19] [1,4]-Wittig rearrangement of the [1-(benzyloxy)allyl]silane 18 affords an enolate intermediate 19 that can be trapped with different electrophiles to yield α-substituted acyltrimethylsilane products 20 (▶ Scheme 10).[19] Alkylation, benzylation, and methylation give the C-alkylated products 20 in good yields, but when the enolate 19 is trapped with iodoethane or 1-iodopropane 3:1 mixtures of the C- and O-alkylated products are isolated.

▶ Scheme 10 [1,4]-Wittig Rearrangement–Enolate Trapping[19]

R

1

X

Yield (%)

Ref

CH

2

CH=CH

2

Br

55

[

19

]

Bn

Br

66

[

19

]

Me

I

73

[

19

]

A Peterson alkenation/vinyl sulfide acidic hydrolysis provides an alternative to the dithiane method of acylsilane synthesis. Bis(silylated) methylsulfanyl derivatives 21, prepared from (methylsulfanyl)(trimethylsilyl)methanes,[20] react with butyllithium and an appropriate aldehyde to give diastereomeric mixtures of vinylsilanes 22 in reasonable yield.[21] The vinyl sulfide functionality cleanly, albeit slowly, hydrolyzes to the acylsilane 23 using aqueous hydrochloric acid in acetone (▶ Scheme 11).[21]

▶ Scheme 11 Preparation of Acylsilanes from Bis(silylated) Methylsulfanyl Derivatives[21]

α-(Alkyl)acylsilanes 20; General Procedure:[19]

A soln of [1-(benzyloxy)allyl]silane 18 (76 mg, 0.34 mmol) in freshly distilled anhyd THF (4.5 mL) was cooled to −78 °C under N2. A 1.3 M soln of s-BuLi in cyclohexane (0.4 mL, 0.52 mmol, 1.5 equiv) was added dropwise via syringe. The mixture was stirred for 30 min at −78 °C and the resultant enolate soln was transferred via cannula to a THF soln of the electrophile at −78 °C with monitoring by TLC. The mixture was then quenched with sat. aq NH4Cl and diluted with Et2O. The phases were separated and the organic phase was washed with H2O and brine. The organic phase was dried (MgSO4) and the solvent was removed. The residue was purified by column chromatography (silica gel, EtOAc/hexane 0:100 to 2:98); yield: 55–73%.

4.4.25.11.1.2 Method 2: Synthesis of Bis(acylsilanes)

A variant of the oxidative hydrolysis of dithianes[23] has been employed to synthesize 1,4-bis(acylsilanes).[22] Bis(dithianes) 26 are synthesized by two methods. The less encumbered trimethylsilyl derivatives are isolated in moderate to good yields by reacting 2-(trimethylsilyl)-1,3-dithiane (24) via 2-(trimethylsilyl)-1,3-dithian-2-yllithium with 1,2-bis(trifluoromethanesulfonates) 25 (▶ Scheme 12).[22] Competing elimination reactions occur when the two trifluoromethanesulfonate groups are bonded to secondary carbon atoms.

▶ Scheme 12 Synthesis of 1,2-Bis(2-trimethylsilyl-1,3-dithian-2-yl)ethanes[22]

R

1

R

2

Yield (%)

Ref

H

H

65

[

22

]

Me

H

37

[

22

]

Me

Me

42

[

22

]

▶ Scheme 13 Synthesis of More Hindered and Unsymmetrical Bis(dithianes)[22,24]

R

1

R

2

Yield (%) of 28

Ref

Me

Me

78

[

22

,

24

]

Et

Et

86

[

22

,

24

]

t

-Bu

Me

47

[

22

,

24

]

iPr

iPr

81

[

22

,

24

]

n

R

1

R

2

Yield (%) of 29

Ref

1

Et

Et

88

[

24

]

1

t

-Bu

Me

75

[

24

]

1

iPr

iPr

91

[

24

]

2

iPr

iPr

78

[

24

]

▶ Scheme 14 Synthesis of Bis(acylsilanes)[24]

n

R

1

R

2

R

3

R

4

Conditions

Yield (%)

Ref

1

Me

Me

Me

Me

MeI, CaCO

3

, MeCN/H

2

O (1:1), 55 °C, 8–15 h

90

[

24

]

1

Et

Et

Et

Et

Hg(ClO

4

)

2

•H

2

O, CaCO

3

, THF/H

2

O (4:1), rt, overnight

80

[

24

]

1

t

-Bu

Me

Me

t

-Bu

Hg(ClO

4

)

2

•H

2

O, CaCO

3

, THF/H

2

O (4:1), rt, overnight

86

[

24

]

1

iPr

iPr

iPr

iPr

Hg(ClO

4

)

2

•H

2

O, CaCO

3

, THF/H

2

O (4:1), rt, overnight

61

[

24

]

1

Me

Me

Et

Et

Hg(ClO

4

)

2

•H

2

O, CaCO

3

, THF/H

2

O (4:1), rt, overnight

72

[

24

]

1

Me

Me

Me

t

-Bu

Hg(ClO

4

)

2

•H

2

O, CaCO

3

, THF/H

2

O (4:1), rt, overnight

63

[

24

]

1

Me

Me

iPr

iPr

Hg(ClO

4

)

2

•H

2

O, CaCO

3

, THF/H

2

O (4:1), rt, overnight

74

[

24

]

2

Me

Me

iPr

iPr

Hg(ClO

4

)

2

•H

2

O, CaCO

3

, THF/H

2

O (4:1), rt, overnight

53

[

24

]

▶ Scheme 15 Synthesis of 1,5-Bis(acylsilanes) with 1,3-Dihalopropanes[24]

R

1

R

2

R

3

R

4

R

5

X

Z

Yield (%) of 32

Hydrolysis Conditions

Yield (%) of 33

Ref

Me

Me

H

Me

Me

I

I

91

MeI, CaCO

3

75

[

24

]

t

-Bu

Me

H

Me

t

-Bu

I

I

86

I

2

, CaCO

3

97

[

24

]

Me

Me

H

Ph

Me

Cl

I

82

Hg(ClO

4

)

2

, CaCO

3

59

[

24

]

Et

Et

H

Me

t

-Bu

Cl

I

66

Hg(ClO

4

)

2

, CaCO

3

77

[

24

]

Me

Me

Me

Me

Me

Br

Br

85

Hg(ClO

4

)

2

, CaCO

3

79

[

24

]

t

-Bu

Me

Me

Me

t

-Bu

I

I

36

I

2

, CaCO

3

90

[

24

]

The synthesis of type-2 bis(acylsilanes), where the silicon moieties exist between two carbonyl functional groups has been described. Benzotriazole-substituted compound 34 can be catalytically converted into 1,6-disilahex-3-ene 35 using the Grubbs II catalyst in refluxing dichloromethane.[5] Compound 35 is isolated in 52% yield as a 3:2 mixture of stereoisomers and can be converted into the desired type 2 bis(acylsilane) 36 upon treatment with iron(III) chloride in acetone (▶ Scheme 16).[5]

▶ Scheme 16 Synthesis of a Type-2 Bis(acylsilane) via Self Cross-Metathesis Reaction[5]

Benzotriazole-substituted compounds 38 are synthesized via a Katritzky-type strategy[25] from 1-(phenoxymethyl)-1H-benzotriazole (37) and can be further converted into vinyl and allyl acylsilanes 39 in variable yields (▶ Scheme 17).[5]

▶ Scheme 17 Synthesis of Acyl(allyl)- and Acyl(vinyl)silanes[5]

R

1

R

2

Yield (%) of 38

Yield (%) of 39

Ref

(CH

2

)

9

Me

CH

2

CH=CH

2

70

95

[

5

]

CH

2

CH=CH

2

CH

2

CH=CH

2

75

25

[

5

]

(CH

2

)

3

CH=CH

2

CH

2

CH=CH

2

58

80

[

5

]

(CH

2

)

9

Me

CH=CH

2

60

94

[

5

]

CH

2

CH=CH

2

CH=CH

2

65

35

[

5

]

4.4.25.11.1.3 Method 3: Synthesis of α-Oxo Acylsilanes