Science of Synthesis: Knowledge Updates 2018 Vol. 3 E-Book

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

Seitenzahl: 903

Veröffentlichungsjahr: 2018

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. Four annual volumes updating content across all categories ensure that you always have access to state-of-the-art synthetic methodology.

Leseprobe

Science of Synthesis

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

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

Methods critically evaluated by leading scientists

Background information and detailed experimental procedures

Schemes and tables which illustrate the reaction scope

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Library of Congress Cataloging in Publication Data

Science of synthesis : Houben–Weyl methods of molecular transformations.     p. cm.   Includes bibliographical references.   Contents: Science of Synthesis Knowledge Updates 2018/3 / volume editors, M. C. Bagley, K. Banert, J. A. Joule. T. Murai, C. A. Ramsden   ISBN 978-3-13-242321-3   1. Organic compounds–Synthesis. I. Title: Houben–Weyl methods of molecular transformations.   QD262.S35 2000547'.2–dc21          00-061560

(Houben–Weyl methods of organic chemistry)

British Library Cataloguing in Publication Data

A catalogue record for this book is available from the British Library

ISSN (print) 2510-5469ISSN (online) 2566-7297

ISBN (print) 978-3-13-242321-3ISBN (PDF) 978-3-13-242322-0ISBN (EPUB) 978-3-13-242323-7DOI 10.1055/b-006-161208

Structure searchable version available at: sos.thieme.com

Date of publication: July 11, 2018

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This reference work mentions numerous commercial and proprietary trade names, registered trademarks and the like (not necessarily marked as such), patents, production and manufacturing procedures, registered designs, and designations. The editors and publishers wish to point out very clearly that the present legal situation in respect of these names or designations or trademarks must be carefully examined before making any commercial use of the same. Industrially produced apparatus and equipment are included to a necessarily restricted extent only and any exclusion of products not mentioned in this reference work does not imply that any such selection of exclusion has been based on quality criteria or quality considerations.

Warning! Read carefully the following: Although this reference work has been written by experts, the user must be advised that the handling of chemicals, microorganisms, and chemical apparatus carries potentially life-threatening risks. For example, serious dangers could occur through quantities being incorrectly given. The authors took the utmost care that the quantities and experimental details described herein reflected the current state of the art of science when the work was published. However, the authors, editors, and publishers take no responsibility as to the correctness of the content. Further, scientific knowledge is constantly changing. As new information becomes available, the user must consult it. Although the authors, publishers, and editors took great care in publishing this work, it is possible that typographical errors exist, including errors in the formulas given herein. Therefore, it is imperative that and the responsibility of every user to carefully check whether quantities, experimental details, or other information given herein are correct based on the user s own understanding as a scientist. Scale-up of experimental procedures published in Science of Synthesis

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 expert-evaluated 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

10.2 Product Class 2: Benzo[c]furan and Its Derivatives

H. Kwiecień

This chapter is a revision of the earlier Science of Synthesis contribution describing methods for the synthesis of benzo[c]furans (isobenzofurans), and has been expanded to include 1,3-dihydrobenzo[c]furan-1(3H)-ones [1,3-dihydroisobenzofuran-1(3H)-ones, phthalides]. Various methods for the in situ generation of the very reactive benzo[c]furans and their trapping with dienophiles through Diels–Alder reactions, as well as approaches to the preparation of stable 1,3-diarylbenzo[c]furans, are presented. Classical routes to 1,3-dihydrobenzo[c]furan-1(3H)-ones involve the disproportionation of 1,2-diacylbenzenes or formation of the lactone ring from 2-functionalized benzoic acid derivatives. More recent developments that involve other approaches are also included.

Keywords: benzo[c]furans • isobenzofurans • 1,3-dihydrobenzo[c]furan-1(3H)-ones • phthalides • organometallic reagents • transition-metal catalysts • cyclization • Diels–Alder cycloaddition • retro-Diels–Alder reaction • lactonization • pyrolysis • asymmetric reaction • ring transformation • aromatization

15.6.3 Isoquinolinones

V. A. Glushkov and Yu. V. Shklyaev

This chapter is an update to the earlier Science of Synthesis contribution describing methods for the synthesis of isoquinolin-1(2H)-ones and isoquinolin-3(2H)-ones. The focus is on the literature published in the period 2005–2015, and includes new cyclization reactions, C—H activation methods, and catalysis by metal complexes of nickel, ruthenium, rhodium, and palladium.

Keywords: isoquinolines • isoquinolinones • benzamides • cyclization • lactamization • C—H bond activation • annulation • acetylenes • transition-metal catalysis • nickel • ruthenium • rhodium • palladium

18.10.15 Thiocarbonic Acids and Derivatives

R. A. Aitken

This chapter is an update to the earlier Science of Synthesis contribution (Section 18.10) describing methods for the synthesis of thiocarbonic acids and derivatives and their applications in organic synthesis. In addition to new methods and applications for the more common derivatives covered in the original chapter, synthesis and applications of several less common systems are included for the first time.

Keywords: sulfur compounds • selenium compounds • tellurium compounds • thiocarbonyl compounds • thiocarbamates • thionyl compounds • thioureas • dithiocarbonates • dithiocarbamates

30.3.4.3 1,3-Dithianes

Y. Saikawa and M. Nakata

1,3-Dithianes are widely used as carbonyl protecting groups as they are stable under both acidic and basic conditions. They are intermediates in desulfurization reactions and they also enable carbonyl umpolung by metalation. This chapter discusses advances in 1,3-dithiane synthesis published since 2007, including solid-supported thioacetalization reactions.

Keywords: acetalization • umpolung • dithianes • metalation • dithiols

30.3.5.3 1,3-Dithiepanes

Y. Saikawa and M. Nakata

1,3-Dithiepanes are less common than 1,3-dithiolanes or 1,3-dithianes, but are also used in the thioacetalization of carbonyl compounds. This chapter covers methods published since 2007, including fused rings with hidden 1,3-dithiepane substructures.

Keywords: dithiepanes • Lewis acid catalyzed reactions • acetalization • fused-ring systems • dithiols

30.4.3 S,N-Acetals (α-Amino Sulfur Derivatives)

Y. Mutoh

This chapter is an update to the earlier Science of Synthesis contribution (Section 30.4) describing methods for the synthesis of S,N-acetals (also known as N,S-acetals or α-amino sulfur derivatives) that have been reported since 2003. One of the major recent developments involves the enantioselective synthesis of S,N-acetals by organocatalysis.

Keywords:S,N-acetals • α-amino sulfur derivatives • alkynylation • nucleophilic addition • phase-transfer catalysis • asymmetric catalysis • acid catalysts • electrophilic additions • cycloadditions • sulfur compounds • thiols • iminium salts

30.6.3 N,N-Acetals (Aminals)

Y. Mutoh

This chapter is an update to the earlier Science of Synthesis contribution (Section 30.6) describing methods for the synthesis of N,N-acetals (also known as aminals) that have been reported since 2003. The major recent advances include methods for the enantioselective synthesis of N,N-acetals by organocatalysis and by transition-metal catalysis.

Keywords:N,N-acetals • aminals • alkylation • nucleophilic addition • asymmetric catalysis • acid catalysts • electrophilic additions • cycloadditions • hetero-Diels–Alder reactions • imines • palladium catalysts • iridium catalysts

31.5.1.5.12 Synthesis of Phenols from Nonaromatic Precursors

C. González-Bello

The introduction, or chemical modification, of substituents on an existing aromatic ring is probably the most widely employed strategy for the synthesis of phenols, and these methods are summarized in Sections 31.5.1.1 to 31.5.1.4. However, with such transformations, it is sometimes difficult to achieve satisfactory regiocontrol. Furthermore, the required precursors may be expensive, difficult to synthesize, or simply unavailable. The direct construction of a phenol ring from acyclic precursors that already bear the required substituents at the appropriate positions represents a good alternative. This strategy is particularly useful for the synthesis of highly substituted phenols. In this chapter, an update of the reported methods for this approach, which were originally described in Section 31.5.1.5 of Science of Synthesis in 2007, is provided, and includes methods for benzannulation, cycloaromatization, cyclocondensation, and ring-closing metathesis.

Keywords: phenols • benzannulation • cycloaromatization • cyclizations • cyclocondensation • ring-closing metathesis • Diels–Alder reactions

Science of Synthesis Knowledge Updates 2018/3

Preface

Abstracts

Table of Contents

10.2 Product Class 2: Benzo[c]furan and Its Derivatives

H. Kwiecień

15.6.3 Isoquinolinones (Update 2018)

V. A. Glushkov and Yu. V. Shklyaev

18.10.15 Thiocarbonic Acids and Derivatives (Update 2018)

R. A. Aitken

30.3.4.3 1,3-Dithianes (Update 2018)

Y. Saikawa and M. Nakata

30.3.5.3 1,3-Dithiepanes (Update 2018)

Y. Saikawa and M. Nakata

30.4.3 S, N-Acetals (α-Amino Sulfur Derivatives) (Update 2018)

Y. Mutoh

30.6.3 N, N-Acetals (Aminals) (Update 2018)

Y. Mutoh

31.5.1.5.12 Synthesis of Phenols from Nonaromatic Precursors (Update 2018)

C. González-Bello

Author Index

Abbreviations

Table of Contents

Volume 10: Fused Five-Membered Hetarenes with One Heteroatom

10.2 Product Class 2: Benzo[c]furan and Its Derivatives

H. Kwiecień

10.2 Product Class 2: Benzo[c]furan and Its Derivatives

10.2.1 Product Subclass 1: Benzo[c]furans

10.2.1.1 Synthesis by Ring-Closure Reactions

10.2.1.1.1 Annulation to an Arene

10.2.1.1.1.1 Formation of One O—C and One C—C Bond

10.2.1.1.1.1.1 Method 1: From Aromatic Ketimines and Aldehydes by Rhenium Catalysis

10.2.1.1.1.1.1.1 Variation 1: From Ketimines and Benzyl Alcohol

10.2.1.1.1.2 Formation of One O—C Bond

10.2.1.1.1.2.1 Method 1: From 2-Alkynylbenzyl Alcohols or Their Derivatives

10.2.1.1.1.2.1.1 Variation 1: From 2-Alkynylbenzyl Alcohols Using a Palladium Catalyst

10.2.1.1.1.2.1.2 Variation 2: From 2-Alkynylbenzyl Alcohols or O-Silylated Derivatives and an Aryl Iodide Using a Palladium Catalyst

10.2.1.1.1.2.1.3 Variation 3: From 2-Ethynylbenzyl Alcohols via Carbocyclization with Aryl Iodides and Carbon Monoxide Using a Palladium Catalyst under Basic Conditions

10.2.1.1.1.2.2 Method 2: From (2-Alkynylaryl)aldehydes and Ketones and Fischer Carbene Complexes

10.2.1.1.1.2.2.1 Variation 1: From (2-Alkynylaryl)aldehydes or 2-Alkynylaryl Ketones and Fischer Carbene Complexes

10.2.1.1.1.2.2.2 Variation 2: From 2-Alkynylaldehydes and Chromium–Dicyanocarbene Complexes

10.2.1.1.1.2.2.3 Variation 3: From 2-Enynylbenzaldehydes and a Chromium–Carbene Complex

10.2.1.1.1.2.2.4 Variation 4: From 2-Ethynyl-N,N-dimethylbenzamide and a Fischer Carbene Complex

10.2.1.1.1.2.3 Method 3: From 2-Ethynylbenzoyl–Rhenium Complexes

10.2.1.1.1.2.4 Method 4: From 2-Alkynylbenzaldehydes by Palladium-Catalyzed Cycloreduction

10.2.1.1.1.2.5 Method 5: From Bis(2-aroylphenyl)acetylenes by Photochemical Exocyclic [2 + 2 + 2] Cycloaddition

10.2.1.1.1.2.6 Method 6: From 2-Alkenylbenzaldehydes

10.2.1.1.1.2.7 Method 7: From Acetals of 2-(Hydroxymethyl)benzaldehydes

10.2.1.1.1.2.8 Method 8: From 2-Acylbenzyl Alcohols

10.2.1.1.1.2.9 Method 9: From 1,2-Diacylbenzenes

10.2.1.1.1.2.9.1 Variation 1: Reduction with Borohydrides

10.2.1.1.1.2.9.2 Variation 2: Reduction with Dissolving Metals

10.2.1.1.1.2.9.3 Variation 3: From Phthalaldehyde and Trialkyl Phosphites Promoted by Lewis Acids

10.2.1.1.1.2.9.4 Variation 4: From Phthalaldehyde and Triethylsilane with a Scandium Catalyst

10.2.1.1.1.2.9.5 Variation 5: From 2-Aroylbenzaldehydes with Arylmagnesium Reagents

10.2.1.1.1.2.9.6 Variation 6: From 2-Benzoylbenzaldehyde with Arylboronic Acids Using Palladium or Rhodium Catalysts

10.2.1.1.1.2.9.7 Variation 7: From 2-Benzoylbenzaldehydes and Trimethylsilyl Cyanide

10.2.1.1.1.2.9.8 Variation 8: From 2-Acylbenzaldehydes and Potassium Cyanide

10.2.1.1.1.2.9.9 Variation 9: From 2-(Alkynylacyl)benzaldehydes

10.2.1.1.1.2.10 Method 10: From 2-Acylbenzyl Sulfoxides

10.2.1.1.1.2.10.1 Variation 1: From 2-Acylbenzyl Sulfoxides via Pummerer Reaction

10.2.1.1.1.2.10.2 Variation 2: From 2-Carbamoylbenzyl Sulfoxides via Pummerer Reaction

10.2.1.1.1.2.11 Method 11: From Methyl 2-Formylbenzoates

10.2.1.1.1.2.12 Method 12: From Derivatives of 2-(Diazomethyl)benzoic Acid

10.2.1.1.1.2.12.1 Variation 1: From Alkyl 2-(Diazomethyl)benzoates

10.2.1.1.1.2.12.2 Variation 2: From a 2-(Diazomethyl)benzamide

10.2.1.1.1.2.12.3 Variation 3: From 2-(Diazomethyl)benzamides and Intramolecular Diels–Alder Cycloaddition Reactions

10.2.1.1.1.2.13 Method 13: From 2-(Halomethyl)benzamides

10.2.1.1.2 Annulation to a Furan Ring

10.2.1.1.2.1 Method 1: From Furan-3,4-dicarbaldehydes via Addition to Conjugated Alkenes

10.2.1.1.2.2 Method 2: From Furan-3,4-dicarbaldehydes via Aldol Condensations

10.2.1.1.2.3 Method 3: From Dimethyl Furan-3,4-dicarboxylate via Claisen Condensation

10.2.1.2 Synthesis by Ring Transformation

10.2.1.2.1 Method 1: Retro-Diels–Alder Reactions

10.2.1.2.1.1 Variation 1: Flash-Vacuum Pyrolysis of 1,2,3,4-Tetrahydro-1,4-epoxynaphthalenes

10.2.1.2.1.2 Variation 2: Thermal Decomposition of Pyranone or Cyclopentadienone Adducts with 1,4-Dihydro-1,4-epoxynaphthalene

10.2.1.2.1.3 Variation 3: From Benzyne/Oxazole Cycloadducts

10.2.1.2.1.4 Variation 4: From 1,4-Dihydro-1,4-epoxynaphthalene/3,6-Di-(pyridin-2-yl)-1,2,4,5-tetrazine Adducts

10.2.1.2.1.5 Variation 5: Ring-Selective Generation of Benzo[c]furans from Unsymmetrically Substituted Diepoxyanthracenes

10.2.1.2.1.6 Variation 6: From Benzobisoxadisiloles or Benzotrisoxadisiloles

10.2.1.2.2 Method 2: From 3,4-Dihydro-1H-benzo[d][1,2]oxazines via Hemiaminals

10.2.1.2.3 Method 3: From Indenone Derivatives

10.2.1.2.4 Method 4: Transformation of a 2H-Indene Ring

10.2.1.3 Aromatization

10.2.1.3.1 Method 1: From 3a,7a-Dihydrobenzo[c]furan-1,3-diones

10.2.1.3.2 Method 2: From 5,6-Dihydrobenzo[c]furan-4,7-diones

10.2.1.3.3 Method 3: From Benzo[c]furan-1(3H)-ones by Deprotonation

10.2.1.3.3.1 Variation 1: From Benzo[c]furan-1(3H)-ones by Deprotonation and Silylation

10.2.1.3.4 Method 4: From Benzo[c]furan-1(3H)-ones by Reduction/Elimination

10.2.1.3.5 Method 5: From Benzo[c]furan-1(3H)-ones and Grignard Reagents

10.2.1.3.6 Method 6: From Benzo[c]furan-1(3H)-ones and Organolithium Reagents

10.2.1.3.7 Method 7: From 1,3-Dihydrobenzo[c]furan-1-ols

10.2.1.3.7.1 Variation 1: Acid-Catalyzed Dehydration of 1,3-Dihydrobenzo[c]furan-1-ols

10.2.1.3.7.2 Variation 2: From a Silylated Hemiacetal with Metal Fluorides

10.2.1.3.7.3 Variation 3: Dehydration by Thermolysis

10.2.1.3.8 Method 8: From 1-Alkoxy-1,3-dihydrobenzo[c]furans

10.2.1.3.8.1 Variation 1: Via Base-Promoted 1,4-Elimination

10.2.1.3.8.2 Variation 2: Via Acid-Catalyzed 1,4-Elimination

10.2.1.3.8.3 Variation 3: Via Palladium-Catalyzed Reaction under Neutral Conditions

10.2.1.3.9 Method 9: From 1,1-Dimethoxy-1,3-dihydrobenzo[c]furan

10.2.1.3.10 Method 10: From 1,3-Dihydrobenzo[c]furan-1-amines

10.2.1.3.11 Method 11: From 1-Alkylidene-1,3-dihydrobenzo[c]furans

10.2.1.3.12 Method 12: By Aromatization of the Benzene Ring

10.2.1.3.12.1 Variation 1: By Dehydrogenation of Partially Hydrogenated Areno[c]furans

10.2.1.3.12.2 Variation 2: From a 5,6-Dibromo-4,5,6,7-tetrahydrobenzo[c]furan by Dehydrobromination

10.2.1.3.12.3 Variation 3: By Dehydration of the Partially Reduced Arene Ring of Hydroxyareno[c]furans

10.2.1.3.12.4 Variation 4: From 6,7-Dihydrobenzo[c]furan-4(5H)-ones by Dehydrogenation

10.2.1.3.12.5 Variation 5: From Benzo[c]furan-4,7-diones by Reduction

10.2.1.3.13 Method 13: From 4,5-Diaroylcyclohexenes

10.2.1.3.14 Method 14: From 1,2-Diaroylcyclohexadienes

10.2.1.4 Synthesis by Substituent Modification

10.2.1.4.1 Method 1: Giving Benzo[c]furans Substituted on the Furan Ring

10.2.2 Product Subclass 2: Benzo[c]furan-1(3H)-ones

10.2.2.1 Synthesis by Ring-Closure Reactions: Annulation to an Arene

10.2.2.1.1 By Formation of One O—C and One C—C Bond

10.2.2.1.1.1 With Formation of 1—2 and 1—7a Bonds

10.2.2.1.1.1.1 Method 1: From Benzyl Alcohols via Lithiation/Carbonylation

10.2.2.1.1.1.2 Method 2: From Benzyl Alcohols via Thallation/Carbonylation

10.2.2.1.1.1.3 Method 3: From 2-Halo- or 2-[(Trifluoromethylsulfonyl)oxy]benzyl Alcohols via Carbonylation

10.2.2.1.1.1.3.1 Variation 1: With Use of a Palladium Catalyst and Carbon Monoxide

10.2.2.1.1.1.3.2 Variation 2: Via Cyanation with Use of Copper Catalysis

10.2.2.1.1.1.3.3 Variation 3: Via Palladium Catalysis Using Paraformaldehyde as Carbonyl Group Source

10.2.2.1.1.1.3.4 Variation 4: Via Palladium-Catalyzed Carbonylation of 2-Halobenzyl Alcohols Using 2-Phenyloxirane as Carbonyl Group Source

10.2.2.1.1.1.3.5 Variation 5: Via Palladium Catalysis Using a Cobalt–Carbonyl Complex

10.2.2.1.1.1.3.6 Variation 6: Via Palladium Catalysis Using Phenyl Formate as Carbonyl Group Source

10.2.2.1.1.2 With Formation of 2—3 and 3—3a Bonds

10.2.2.1.1.2.1 Method 1: From Benzoic Acids via Palladium-Catalyzed Alkylation with Alkyl Halides

10.2.2.1.1.2.2 Method 2: From Benzoic Acids via Ruthenium-Catalyzed C—H Bond Alkenylation

10.2.2.1.1.2.3 Method 3: From 2-Iodobenzoic Acid and Alkynes

10.2.2.1.1.3 With Formation of 1—2 and 3—3a Bonds

10.2.2.1.1.3.1 Method 1: From Palladium-Catalyzed Hydroxymethylation of Arylboronic Acids Using Aqueous Formaldehyde

10.2.2.1.1.3.2 Method 2: From 2-Iodobenzoates via Cobalt-Catalyzed Reaction with Aldehydes

10.2.2.1.1.3.3 Method 3: From 2-Halobenzoic Acid Derivatives Using [Diisopropoxy(methyl)silyl]methyl Grignard Reagent as Hydroxymethylating Agent

10.2.2.1.2 By Formation of One O—C Bond

10.2.2.1.2.1 With Formation of the 1—2 Bond

10.2.2.1.2.1.1 Method 1: From (2-Vinylphenyl)methanol

10.2.2.1.2.1.2 Method 2: By Oxidation of 1,2-Bis(hydroxymethyl)benzenes

10.2.2.1.2.1.2.1 Variation 1: Using Tungstic Acid as Catalyst

10.2.2.1.2.1.2.2 Variation 2: Using an Iridium Complex as Catalyst

10.2.2.1.2.1.2.3 Variation 3: Using Pyridinium Chlorochromate as Catalyst

10.2.2.1.2.1.2.4 Variation 4: Via Copper/Nitroxyl Catalysis

10.2.2.1.2.1.2.5 Variation 5: Using 2-Iodo-3,4,5,6-tetramethylbenzoic Acid and Oxone

10.2.2.1.2.1.2.6 Variation 6: Iron-Catalyzed Aerobic Oxidation Using Molecular Oxygen or Air

10.2.2.1.2.1.3 Method 3: From Arene-1,2-dicarbaldehydes or 2-Acylbenzaldehydes

10.2.2.1.2.1.3.1 Variation 1: By Disproportionation Using a Ruthenium Hydride Complex

10.2.2.1.2.1.3.2 Variation 2: By Disproportionation with 3-(2-Oxoalkylation) Using a Ruthenium Hydride Complex

10.2.2.1.2.1.3.3 Variation 3: By Disproportionation Using a Rhodium Complex

10.2.2.1.2.1.3.4 Variation 4: By Rhodium/Copper Catalyzed Oxidative Cyclization with 3-Alkoxylation

10.2.2.1.2.1.3.5 Variation 5: By Rhodium/Copper Catalyzed Oxidative Cyclization with 3-(1,3-Dioxoalkylation)

10.2.2.1.2.1.3.6 Variation 6: By Palladium- or Rhodium-Catalyzed Reaction with Organoboronic Acids with 3-Arylation

10.2.2.1.2.1.3.7 Variation 7: By Cobalt-Catalyzed Reaction with Arylboronic Acids with 3-Arylation

10.2.2.1.2.1.3.8 Variation 8: By Disproportionation Using Sodium Cyanide or UV Irradiation

10.2.2.1.2.1.4 Method 4: From 2-Formyl- or 2-Aroylbenzoic Acids

10.2.2.1.2.1.4.1 Variation 1: By Reaction with Acetophenones under Solid Acid Catalysis and Microwave Irradiation

10.2.2.1.2.1.4.2 Variation 2: By Reaction with 1,3-Dicarbonyl Compounds under Solid Acid Catalysis and Heating

10.2.2.1.2.1.4.3 Variation 3: With Introduction of a Heterocycle at the C3 Position

10.2.2.1.2.1.5 Method 5: From Alkyl 2-Formylbenzoates by Palladium-Catalyzed Reaction with Organoboronic Acids

10.2.2.1.2.1.6 Method 6: From Alkyl 2-Formylbenzoates by Palladium-Catalyzed Asymmetric Reaction with Organoboronic Acids

10.2.2.1.2.1.7 Method 7: By Partial Reduction of Esters of Phthalic Acids (Alkyl Phthalates)

10.2.2.1.2.1.8 Method 8: From 2-Formylbenzonitriles by Reaction with a Nucleophile

10.2.2.1.2.2 With Formation of the 2—3 Bond

10.2.2.1.2.2.1 Method 1: From 2-Alkylbenzoic Acids by Intramolecular Aryloxylation of C(sp3)—H Bonds

10.2.2.1.2.2.1.1 Variation 1: By Platinum Catalysis

10.2.2.1.2.2.1.2 Variation 2: By Selenium-Catalysis

10.2.2.1.2.2.1.3 Variation 3: Using Organohypervalent Iodine(III)/Molecular Iodine Reagents with Irradiation

10.2.2.1.2.2.1.4 Variation 4: Using Hypervalent Iodine(III)/Potassium Bromide Reagents

10.2.2.1.2.2.1.5 Variation 5: Using Sodium Bromate and Sodium Hydrogen Sulfite

10.2.2.1.2.2.2 Method 2: From Functionalized Alkyl 2-Alkylbenzoates

10.2.2.1.2.2.2.1 Variation 1: By Trifluoroacetic Acid Mediated Lactonization

10.2.2.1.2.2.2.2 Variation 2: By Cyclization of 2-(Halomethyl)benzoates

10.2.2.1.2.2.3 Method 3: From 2-Alkenylbenzoic Acids

10.2.2.1.2.2.3.1 Variation 1: By Lactonization with Chlorination

10.2.2.1.2.2.3.2 Variation 2: By Asymmetric Lactonization with Chlorination

10.2.2.1.2.2.3.3 Variation 3: By Lactonization with Thiocyanation

10.2.2.1.2.2.3.4 Variation 4: By Asymmetric Lactonization with Fluorination through Anion Phase Transfer

10.2.2.1.2.2.3.5 Variation 5: By Lactonization with Fluorination Using a Bifunctional Hydroxy–Carboxylate Catalyst

10.2.2.1.2.2.4 Method 4: From 2-Alkenylbenzamides by Diastereoselective Iodocyclization

10.2.2.1.2.2.5 Method 5: From 2-Alkynylbenzoic Acids by Base-Catalyzed Cyclization

10.2.2.1.2.2.6 Method 6: From 2-Alkynylbenzoic Acids and Aryl Halides by Palladium-Catalyzed Cyclization in the Presence of an Inorganic Base

10.2.2.1.2.2.7 Method 7: From Alkyl 2-Alkynylbenzoates

10.2.2.1.2.2.7.1 Variation 1: By Lactonization and Iodination

10.2.2.1.2.2.7.2 Variation 2: By Palladium-Catalyzed Cyclization

10.2.2.1.2.2.7.3 Variation 3: By Copper(II) Chloride Mediated Cyclization of N-Alkoxy-2-alkynylbenzamides with Halogenation

10.2.2.1.3 By Formation of One C—C Bond

10.2.2.1.3.1 With Formation of the 3—3a Bond

10.2.2.1.3.1.1 Method 1: From Vinyl 2-Bromobenzoates

10.2.2.2 Synthesis by Ring Transformation

10.2.2.2.1 Method 1: From 3-(tert-Butoxycarbonyl)-1H-benzo[d][1,2]oxazine-1,4(3H)-dione

10.2.2.2.2 Method 2: From Naphthalene by Ozonolysis

10.2.2.2.3 Method 3: From Indane Derivatives in Subcritical Media

10.2.2.2.4 Method 4: From 1,3-Dihydrobenzo[c]furan via Oxidation

10.2.2.2.5 Method 5: From Benzo[c]furan-1(3H)-imines by Hydrolysis

10.2.2.3 Synthesis by Substituent Modification

10.2.2.3.1 Method 1: Synthesis and Reactions of C-Halogen Benzo[c]furan-1(3H)-ones

Volume 15: Six-Membered Hetarenes with One Nitrogen or Phosphorus Atom

15.6 Product Class 6: Isoquinolinones

15.6.3 Isoquinolinones

V. A. Glushkov and Yu. V. Shklyaev

15.6.3 Isoquinolinones

15.6.3.1 Isoquinolin-1(2H)-ones

15.6.3.1.1 Synthesis by Ring-Closure Reactions

15.6.3.1.1.1 By Formation of Three Bonds

15.6.3.1.1.1.1 Method 1: Palladium-Catalyzed Amination/Carbonylation/Cyclization Reaction of 1-Bromo-2-(2-bromovinyl)benzenes

15.6.3.1.1.1.2 Method 2: Carbonylation/Decarboxylation of Diethyl 2-(2-Iodoaryl)malonates with Imines or Imidoyl Chlorides

15.6.3.1.1.1.3 Method 3: Copper-Catalyzed Three-Component Coupling of 2-Halobenzoic Acids, Alkynylcarboxylic Acids, and Ammonium Acetate

15.6.3.1.1.1.4 Method 4: Three-Component Palladium-Catalyzed Condensation of 2-Iodobenzoates, Substituted Allenes, and Ammonium Tartrate

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

15.6.3.1.1.2.1 Method 1: Catalytic Carbonylation of N-Unprotected and N-Monosubstituted 2-Arylethylamines

15.6.3.1.1.2.2 Method 2: From 2-(Acylamino)-2-(2-bromophenyl)acetamides and tert-Butyl Isocyanide

15.6.3.1.1.2.3 Method 3: Reaction of α-Substituted 2-Lithio-β-methoxystyrenes with Isocyanates with Subsequent Cyclization

15.6.3.1.1.2.4 Method 4: From N,N-Diethyl-2-methylbenzamides and Arenecarbonitriles or Hydrazones

15.6.3.1.1.2.5 Method 5: From 2-(Nitromethyl)benzaldehydes and Imines

15.6.3.1.1.2.6 Method 6: From (2-Carboxybenzyl)triphenylphosphonium Bromide by a Sequential Ugi/Wittig Process

15.6.3.1.1.2.7 Method 7: From β-Enamino Esters and 2-Fluorobenzoyl Chlorides

15.6.3.1.1.2.8 Method 8: From 2-Methylbenzamides and Dimethylformamide Dimethyl Acetal

15.6.3.1.1.2.9 Method 9: Iodine(III)-Promoted Dehydrogenative Annulation of Benzamide Derivatives with Alkynes

15.6.3.1.1.2.10 Method 10: Photostimulated Reaction of 2-Iodobenzamide with Enolates

15.6.3.1.1.2.11 Method 11: Cobalt-Catalyzed Quinolinamine-Directed C(sp2)—H Activation with Alkenes

15.6.3.1.1.2.12 Method 12: Nickel-Catalyzed Annulation of Benzamides with Alkynes

15.6.3.1.1.2.13 Method 13: Nickel-Catalyzed Denitrogenative Insertion of Alkenes and Alkynes into 1,2,3-Benzotriazin-4(3H)-ones

15.6.3.1.1.2.14 Method 14: Copper-Mediated Coupling of Benzamides and 2-Halobenzamides

15.6.3.1.1.2.14.1 Variation 1: Coupling of Alkynes with 2-Halobenzamides

15.6.3.1.1.2.14.2 Variation 2: Coupling of Enolates with 2-Halobenzamides

15.6.3.1.1.2.14.3 Variation 3: Coupling of N-(Quinolin-8-yl)benzamides and Cyanoacetates with C—H Activation

15.6.3.1.1.2.15 Method 15: Ruthenium(II)-Catalyzed Oxidative C—H Activation

15.6.3.1.1.2.15.1 Variation 1: Reaction of Benzamides with Alkynes

15.6.3.1.1.2.15.2 Variation 2: Reaction of Hydroxamic Acids and N-Methoxyamides with Alkynes

15.6.3.1.1.2.16 Method 16: Rhodium(III)-Catalyzed Cyclization of Alkenes, Alkynes, and Analogues via C—H Activation

15.6.3.1.1.2.16.1 Variation 1: Annulation with Internal and Terminal Alkynes and 1,3-Diynes

15.6.3.1.1.2.16.2 Variation 2: Annulation of α-Mesyloxy-, α-Tosyloxy-, and α-Haloketones

15.6.3.1.1.2.16.3 Variation 3: Annulation of Diazo Compounds

15.6.3.1.1.2.16.4 Variation 4: Annulation with Alkenes

15.6.3.1.1.2.16.5 Variation 5: Annulation with Ethynyl N-Methyliminodiacetic Acid (MIDA) Boronates or Trifluoro(vinyl)borates

15.6.3.1.1.2.17 Method 17: Palladium-Catalyzed C—H Activation and Intermolecular Annulation

15.6.3.1.1.3 By Formation of One N—C Bond

15.6.3.1.1.3.1 Method 1: From 2-(Cyanomethyl)benzoic Acid

15.6.3.1.1.3.2 Method 2: From Methyl 2-Formylbenzoate and Hippuric Acid

15.6.3.1.1.3.3 Method 3: From 2-Alkynylbenzamides

15.6.3.1.1.3.4 Method 4: Silver(I)-Catalyzed Cyclization of 2-(Alk-1-ynyl)benzaldimines

15.6.3.1.1.3.5 Method 5: From 2-(2-Azidoethyl)benzamides by Staudinger-Type Reaction

15.6.3.1.1.3.6 Method 6: From a 2-(Oxiran-2-ylmethyl)benzonitrile

15.6.3.1.1.4 By Formation of One C—C Bond

15.6.3.1.1.4.1 Method 1: From 2-Arylethanamine Carbamates

15.6.3.1.1.4.2 Method 2: By Cyclization of 2-Arylethyl Isocyanates

15.6.3.1.1.4.3 Method 3: From N-(4-Nitrophenyl)-N′-(2-phenylethyl)ureas

15.6.3.1.1.4.4 Method 4: Cyclization of N-Substituted 2-Aroylbenzamides

15.6.3.1.1.4.5 Method 5: 1,8-Diazabicyclo[5.4.0]undec-7-ene-Promoted Cyclization of 2-(3-Hydroxy-1-alkynyl)benzamides

15.6.3.1.1.4.6 Method 6: Intramolecular Heck Cyclization of N-Allyl-2-iodobenzamides

15.6.3.1.1.4.7 Method 7: Palladium-Catalyzed Cyclization of N-(2-Furylmethyl)-2-iodobenzamides

15.6.3.1.1.4.8 Method 8: Palladium-Catalyzed Cyclization of 2-Bromo-N-cyclopropylbenzamides

15.6.3.1.1.4.9 Method 9: Metathesis of trans-3,4-Diallyl-3,4-dihydropyridin-2(1H)-ones

15.6.3.1.2 Aromatization

15.6.3.1.2.1 Method 1: Intramolecular Diels–Alder Reaction of N-(2-Furylethyl)propynamides

15.6.3.1.3 Synthesis by Ring Transformation

15.6.3.1.3.1 Method 1: Tandem Diels–Alder/Acylation Sequence of Dienamines with Maleic Anhydride

15.6.3.1.3.2 Method 2: From Isoquinolinium Salts, 3,4-Dihydroisoquinolines, and 1,2,3,4-Tetrahydroisoquinolines by Oxidation

15.6.3.1.3.3 Method 3: From Homophthalic Anhydrides

15.6.3.1.3.4 Method 4: From 1H-2-Benzopyran-1-ones and Amines

15.6.3.1.3.5 Method 5: From Benzo[c]furans

15.6.3.1.3.6 Method 6: From 2,3-Dihydro-1H-inden-1-ones by Schmidt Reaction or Beckmann Rearrangement

15.6.3.1.3.7 Method 7: Synthesis of Dihydroisoquinolin-1(2H)-ones by Reduction of Isoquinolin-1(2H)-ones

15.6.3.1.4 Synthesis by Substituent Modification

15.6.3.1.4.1 Substitution of Hydrogen

15.6.3.1.4.1.1 Method 1: Nitration of Isoquinolin-1(2H)-ones

15.6.3.1.4.2 Substitution of Halogens

15.6.3.1.4.2.1 Method 1: Cross-Coupling Reactions

15.6.3.1.4.3 Substitution of Oxygen or Nitrogen

15.6.3.1.4.4 Substitution of Carbon

15.6.3.1.4.5 Modification of Substituents

15.6.3.2 Isoquinolin-3-ones and Isoquinolin-3-ols

15.6.3.2.1 Synthesis by Ring-Closure Reactions

15.6.3.2.1.1 By Formation of Three Bonds

15.6.3.2.1.1.1 Method 1: Palladium-Catalyzed Aromatic Alkylation/Vinylation with Addition Reactions

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

15.6.3.2.1.2.1 Method 1: Ugi Condensation of Monomasked Phthalaldehydes with Amines, Carboxylic Acids, and Isocyanides

15.6.3.2.1.2.2 Method 2: Rhodium-Catalyzed Reaction of N-Methylbenzylamines with Diazomalonate

15.6.3.2.1.3 By Formation of One N—C Bond

15.6.3.2.1.3.1 Method 1: From 2-(2-Cyanoaryl)acetic Acids

15.6.3.2.1.3.2 Method 2: From Ethyl 2-(2-{[(tert-Butylsulfinyl)imino]methyl}phenyl)acetates

15.6.3.2.1.4 By Formation of One C—C Bond

15.6.3.2.1.4.1 Method 1: Friedel–Crafts Cyclization of N-Benzyl-α-bromoamides

15.6.3.2.1.4.2 Method 2: From N-Benzyl-2-(4-hydroxyaryl)acetamides

15.6.3.2.1.4.3 Method 3: From N-Alkynyl-N-benzylamines via C—H Activation and Oxidation

15.6.3.2.1.4.4 Method 4: From N-(2-Iodobenzylamides) of Propynoic Acids

15.6.3.2.2 Synthesis by Substituent Modification

15.6.3.2.2.1 Substitution of Hydrogen

Volume 18: Four Carbon—Heteroatom Bonds: X—C≡X, X=C=X, X2C=X, CX4

18.10 Product Class 10: Thiocarbonic Acids and Derivatives

18.10.15 Thiocarbonic Acids and Derivatives

R. A. Aitken

18.10.15 Thiocarbonic Acids and Derivatives

18.10.15.1 Halothioformate O-Esters

18.10.15.1.1 Synthesis of Halothioformate O-Esters

18.10.15.1.1.1 Method 1: From Tetraethylammonium O-Alkyldithiocarbonates and a Vilsmeier Reagent

18.10.15.1.2 Applications of Halothioformate O-Esters in Organic Synthesis

18.10.15.1.2.1 Method 1: Synthesis of Chlorodifluoromethyl Ethers

18.10.15.2 Halothiocarbonylsulfenyl Halides and Halodithioformate S-Ester S′-Oxides [Chloro(alkylsulfanyl)sulfines]

18.10.15.2.1 Synthesis of Halothiocarbonylsulfenyl Halides and Halodithioformate S-Ester S′-Oxides [Chloro(alkylsulfanyl)sulfines]

18.10.15.2.1.1 Method 1: From Carbon Disulfide and Dihalogens

18.10.15.2.1.2 Method 2: Oxidation of Chlorodithioformates with 3-Chloroperoxybenzoic Acid

18.10.15.3 Thiocarbamoyl Halides

18.10.15.3.1 Synthesis of Thiocarbamoyl Halides

18.10.15.3.1.1 Method 1: From Tetramethylammonium Trifluoromethanethiolate and Secondary Amines

18.10.15.3.1.2 Method 2: From Thiophosgene and a Bicyclic Aziridine

18.10.15.3.2 Applications of Thiocarbamoyl Halides in Organic Synthesis

18.10.15.3.2.1 Method 1: [Bis(polyfluoroalkyl)amino]thiocarbamoyl as a Protecting Group for Alcohols

18.10.15.4 Thiocarbonate O,O-Diesters

18.10.15.4.1 Synthesis of Thiocarbonate O,O-Diesters

18.10.15.4.1.1 Method 1: From Thiophosgene and Two Different Phenols

18.10.15.4.1.2 Method 2: From 1,1′-Thiocarbonyldi(benzotriazole) and Two Different Alcohols or Phenols

18.10.15.4.2 Applications of Thiocarbonate O,O-Diesters in Organic Synthesis

18.10.15.4.2.1 Method 1: Selective Functionalization of Polyols Using O-Phenyl Chlorothioformate

18.10.15.4.2.2 Method 2: Synthesis of 1,1-Difluoroacetals

18.10.15.5 Dithiocarbonate O,S-Diesters

18.10.15.5.1 Synthesis of Dithiocarbonate O,S-Diesters

18.10.15.5.1.1 Method 1: From Carbon Disulfide, an Alcohol, and an Electrophilic Reagent

18.10.15.5.1.2 Method 2: From Epoxides and Carbon Disulfide

18.10.15.5.1.3 Method 3: From Thiophosgene or 1,1′-Thiocarbonyldi(benzotriazole), a Phenol, and a Thiol

18.10.15.5.2 Applications of Dithiocarbonate O,S-Diesters in Organic Synthesis

18.10.15.5.2.1 Method 1: Synthesis of a (Trifluoromethyl)sulfanyl Transfer Reagent

18.10.15.5.2.2 Method 2: Synthesis of Radical-Transfer Agents and Their Addition to Alkenes

18.10.15.5.2.3 Method 3: Addition to N-Acyliminium Salts

18.10.15.6 Thioselenocarbonate O,Se-Diesters

18.10.15.6.1 Synthesis of Thioselenocarbonate O,Se-Diesters

18.10.15.6.1.1 Method 1: From Chlorothioformate O-Esters

18.10.15.6.1.2 Method 2: From Chlorothioselenoformate Se-Esters

18.10.15.7 Thiocarbamate O-Esters

18.10.15.7.1 Synthesis of Thiocarbamate O-Esters

18.10.15.7.1.1 Method 1: From 1,1′-Thiocarbonyldi(benzotriazole), an Amine, and a Phenol or an Alcohol

18.10.15.7.1.2 Method 2: From a Chlorothioformate O-Ester and a Sulfoximine

18.10.15.7.1.3 Method 3: From Tetramethylthiuram Disulfide, Sodium Hydride, and a Phenol

18.10.15.7.2 Applications of Thiocarbamate O-Esters in Organic Synthesis

18.10.15.7.2.1 Method 1: Conversion of Primary Amines into Isothiocyanates

18.10.15.7.2.2 Method 2: Dealkylation of Tertiary Amines

18.10.15.8 Phosphorus-Substituted Thioformates

18.10.15.8.1 Synthesis of Phosphorus-Substituted Thioformates

18.10.15.8.1.1 Method 1: From Carbon Oxysulfide and an Aluminum Phosphide

18.10.15.9 Trithiocarbonates

18.10.15.9.1 Synthesis of Trithiocarbonates

18.10.15.9.1.1 Method 1: S-Oxidation of Trithiocarbonates with 3-Chloroperoxybenzoic Acid

18.10.15.9.1.2 Method 2: From a Chlorodithioformate S-Oxide and a Metal Arenesulfinate

18.10.15.9.2 Applications of Trithiocarbonates in Organic Synthesis

18.10.15.9.2.1 Method 1: Synthesis of 2-Cyanopropan-2-yl Carbonotrithioates for Reversible Addition–Fragmentation Chain-Transfer Polymerization

18.10.15.10 Dithioselenocarbonates and Dithiotellurocarbonates

18.10.15.10.1 Synthesis of Dithioselenocarbonates and Dithiotellurocarbonates

18.10.15.10.1.1 Method 1: From a Selenol or Selenide, Carbon Disulfide, and an Alkyl Halide

18.10.15.10.1.2 Method 2: From a Selenol or Metal Selenide and a Chlorodithioformate

18.10.15.10.1.3 Method 3: From a Thiol and an Se-Alkyl Chlorothioselenoformate

18.10.15.10.1.4 Method 4: Insertion of Carbon Disulfide into M—Se or M—Te Bonds

18.10.15.11 Dithiocarbamates

18.10.15.11.1 Synthesis of Dithiocarbamates

18.10.15.11.1.1 Method 1: From a Thiocarbamoyl Chloride and a Thiol

18.10.15.11.1.2 Method 2: From an Isothiocyanate and a Thiol

18.10.15.11.1.3 Method 3: From a Bicyclic Aziridine and a Chlorodithioformate

18.10.15.11.1.4 Method 4: From 1,1′-Thiocarbonyldi(benzotriazole), a Primary Amine, and a Thiol

18.10.15.11.1.5 Method 5: From an Aminophosphoniodithioformate and Diethylzinc

18.10.15.11.1.6 Method 6: Dimerization of an Amino Acid Derived Isothiocyanate

18.10.15.11.1.7 Method 7: From an Amine, Carbon Disulfide, and a Methyl Alkynoate

18.10.15.11.2 Applications of Dithiocarbamates in Organic Synthesis

18.10.15.11.2.1 Method 1: Synthesis of N-(Trifluoromethyl)amides

18.10.15.11.2.2 Method 2: Synthesis of an S-(2-Cyanopropan-2-yl) Dithiocarbamate for Reversible Addition–Fragmentation Chain-Transfer Polymerization

18.10.15.12 Phosphorus-Substituted Dithioformates

18.10.15.12.1 Synthesis of Phosphorus-Substituted Dithioformates

18.10.15.12.1.1 Method 1: From Dialkyl Phosphites, Carbon Disulfide, and an Alkyl Halide

18.10.15.12.1.2 Method 2: From a (Phenylsulfonylmethyl)phosphonate and Sulfur

18.10.15.12.1.3 Method 3: From a 1-Phospha-3-germaallene and Carbon Disulfide

18.10.15.12.2 Applications of Phosphorus-Substituted Dithioformates in Organic Synthesis

18.10.15.12.2.1 Method 1: S-(1-Phenylethyl) Phosphoryl- and Thiophosphoryldithioformates as Catalysts for Reversible Addition–Fragmentation Chain-Transfer Polymerization

18.10.15.13 Thiodiselenocarbonate Se,Se-Diesters

18.10.15.13.1 Synthesis of Thiodiselenocarbonate Se,Se-Diesters

18.10.15.13.1.1 Method 1: From a Metal Selenolate and Thiophosgene or Thiocarbonyldiimidazole

18.10.15.13.2 Applications of Thiodiselenocarbonate Se,Se-Diesters in Organic Synthesis

18.10.15.13.2.1 Method 1: Synthesis of Reversible Addition–Fragmentation Chain-Transfer Polymerization Agents

18.10.15.13.2.2 Method 2: 1,3-Diselenole-2-thione

18.10.15.14 Thioselenocarbamate Se-Esters and Thiotellurocarbamate Te-Esters

18.10.15.14.1 Synthesis of Thioselenocarbamate Se-Esters and Thiotellurocarbamate Te-Esters

18.10.15.14.1.1 Method 1: From an Isothiocyanate and a Selenol

18.10.15.14.1.2 Method 2: From a Thiocarbamoyl Chloride and a Selenol or Metal Selenide

18.10.15.14.1.3 Method 3: From a Secondary Amine and Carbon Sulfide Selenide

18.10.15.14.1.4 Method 4: From a (2-Aminophenyl)tellurolate and Carbon Disulfide

18.10.15.15 Thioureas and Thiosemicarbazides

18.10.15.15.1 Synthesis of Thioureas and Thiosemicarbazides

18.10.15.15.1.1 Method 1: From a Thiocarbamoyl Chloride and a Sulfoximine

18.10.15.15.1.2 Method 2: From 1,1′-Thiocarbonyldi(benzotriazole) and Two Different Amines

18.10.15.15.1.3 Method 3: From Tetramethylammonium Trifluoromethanethiolate and a Diamine

18.10.15.15.2 Applications of Thioureas and Thiosemicarbazides in Organic Synthesis

18.10.15.15.2.1 Method 1: Synthesis of Chiral Fluorous Organocatalysts

18.10.15.15.2.2 Method 2: Synthesis of Medicinal 2-Thioxoimidazolidin-4-ones

18.10.15.16 Phosphorus-Substituted Carbothioamides

18.10.15.16.1 Synthesis of Phosphorus-Substituted Carbothioamides

18.10.15.16.1.1 Method 1: From Isothiocyanates and PH Nucleophiles

18.10.15.16.1.2 Method 2: From Isothiocyanates and Tertiary Phosphorus Nucleophiles

18.10.15.16.1.3 Method 3: From a (Chloromethyl)phosphine Oxide, an Amine, and Sulfur

18.10.15.16.2 Applications of Phosphorus-Substituted Carbothioamides in Organic Synthesis

18.10.15.16.2.1 Method 1: Synthesis of Nucleoside-Based Enzyme Inhibitors

18.10.15.17 Thiocarbonyldiphosphorus Compounds

18.10.15.17.1 Synthesis of Thiocarbonyldiphosphorus Compounds

18.10.15.17.1.1 Method 1: From Methylenebis(phosphine sulfides), a Base, and Sulfur

18.10.15.17.1.2 Method 2: Disproportionation of Methylenebis(phosphine sulfides)

18.10.15.17.1.3 Method 3: Oxidative Cleavage of a Bis[bis(diphenylphosphino)methanide] Disulfide Complex

Volume 30: Acetals: O/N, S/S, S/N, and N/N and Higher Heteroatom Analogues

30.3 Product Class 3: S,S-Acetals

30.3.4.3 1,3-Dithianes

Y. Saikawa and M. Nakata

30.3.4.3 1,3-Dithianes

30.3.4.3.1 Synthesis of 1,3-Dithianes

30.3.4.3.1.1 Method 1: Thioacetalization of Carbonyl Compounds Using Lewis Acids

30.3.4.3.1.2 Method 2: Thioacetalization of Carbonyl Compounds Using Solid-Supported Catalysts

30.3.4.3.1.3 Method 3: Thioacetalization of Carbonyl Compounds Using Other Catalysts or Reagents

30.3.4.3.1.4 Method 4: Thioacetalization with Polymer-Supported Propane-1,3-dithiol

30.3.4.3.1.5 Method 5: Conjugate Addition of Propane-1,3-dithiol to Alk-1-ynyl Ketones and Esters

30.3.4.3.1.6 Method 6: Metalation or Transmetalation of 1,3-Dithianes

30.3.4.3.1.7 Method 7: Addition of 2-Lithio-1,3-dithiane Derivatives to Epoxides or Aziridines

30.3.4.3.1.8 Method 8: Addition of 2-Metallo-1,3-dithiane Derivatives to C=N Compounds

30.3.4.3.1.9 Method 9: 1,4-Addition Reactions of 2-Metallo-1,3-dithiane Derivatives to α,β-Unsaturated Carbonyl Compounds

30.3.4.3.1.10 Method 10: Asymmetric 1,4-Addition Reactions of 1,3-Dithiane Derivatives to α,β-Unsaturated Compounds

30.3.4.3.1.11 Method 11: Reactions of 2-Silyl-1,3-dithiane Derivatives with Aldehydes and Ketones

30.3.4.3.1.12 Method 12: Reactions of 2-Alkylidene-1,3-dithiane Derivatives

30.3.4.3.1.13 Method 13: Synthesis and Reactions of 1,3-Dithiane 2-Carbocations

30.3.4.3.1.14 Method 14: Synthesis and Reactions of 1,3-Dithiane 2-Carbon Radicals

30.3.4.3.1.15 Method 15: Other Methods

30.3.4.3.2 Applications of 1,3-Dithianes in Organic Syntheses

30.3.4.3.2.1 Method 1: Ring-Expansion Reactions

30.3.5.3 1,3-Dithiepanes

Y. Saikawa and M. Nakata

30.3.5.3 1,3-Dithiepanes

30.3.5.3.1 Method 1: Thioacetalization of Carbonyl Compounds Using Lewis Acids

30.3.5.3.2 Method 2: Miscellaneous Syntheses

30.4 Product Class 4: S, N-Acetals (α-Amino Sulfur Derivatives)

30.4.3 S, N-Acetals (α-Amino Sulfur Derivatives)

Y. Mutoh

30.4.3 S, N-Acetals (α-Amino Sulfur Derivatives)

30.4.3.1 Method 1: Alkynylation of Thioiminium Salts Derived from Thioamides

30.4.3.2 Method 2: Alkylation of Lithium Thiolates from Thioformamides

30.4.3.3 Method 3: Addition of Thiols to N-Acyl Imines by Asymmetric Organocatalysis

30.4.3.4 Method 4: Addition of Thiols to Ketimines by Asymmetric Organocatalysis

30.4.3.5 Method 5: Addition Cyclization Using 1,4-Dithiane-2,5-diol (Formal [3 + 2] Annulation)

30.4.3.6 Method 6: Electrophilic Sulfanylation

30.4.3.7 Method 7: Electrophilic Amination

30.6 Product Class 6: N,N-Acetals

30.6.3 N, N-Acetals (Aminals)

Y. Mutoh

30.6.3 N, N-Acetals (Aminals)

30.6.3.1 Method 1: Tandem Aza-Ene-Type Reaction–Cyclization Cascade

30.6.3.2 Method 2: Alkylation of Aminal Radicals Derived from Amidines and Amidinium Salts under Reductive Conditions

30.6.3.3 Method 3: Lewis Acid Catalyzed [3 + 2]-Cycloannulation Using an Aldehyde, a 2-Aminobenzamide, and a Bis-silyl Dienediolate

30.6.3.4 Method 4: Sequential Aza-Diels–Alder Reaction and Iminium Ion Induced Cyclization

30.6.3.5 Method 5: Imidazolidinone Acid Salt Catalyzed Tandem Allylation–Cyclization

30.6.3.6 Method 6: Transition-Metal-Catalyzed Tandem Allylation–Cyclization

31.5 Product Class 5: Phenols and Phenolates

31.5.1.5.12 Synthesis of Phenols from Nonaromatic Precursors

C. González-Bello

31.5.1.5.12 Synthesis of Phenols from Nonaromatic Precursors

31.5.1.5.12.1 Method 1: Benzannulation Reactions

31.5.1.5.12.1.1 Variation 1: Metal-Free Benzannulation

31.5.1.5.12.1.2 Variation 2: Metal-Catalyzed Benzannulation

31.5.1.5.12.2 Method 2: Cycloaromatization Reactions

31.5.1.5.12.2.1 Variation 1: Diels–Alder Reactions

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

31.5.1.5.12.2.3 Variation 3: Metal-Catalyzed Cycloaromatization Reactions

31.5.1.5.12.2.4 Variation 4: Metal-Catalyzed Cycloisomerization of Enynes Containing Cyclopropenes

31.5.1.5.12.3 Method 3: Cyclocondensation Reactions

31.5.1.5.12.3.1 Variation 1: From Cyclobutenones

31.5.1.5.12.3.2 Variation 2: From α,β-Unsaturated Ketones

31.5.1.5.12.3.3 Variation 3: From Cinnamaldehydes

31.5.1.5.12.3.4 Variation 4: From Allenic Ketones

31.5.1.5.12.4 Method 4: Ring-Closing Metathesis

31.5.1.5.12.4.1 Variation 1: From Triene Ketones

31.5.1.5.12.4.2 Variation 2: From Dienyne Ketones

31.5.1.5.12.4.3 Variation 3: From Hydroxydienones

Author Index

Abbreviations

10.2 Product Class 2: Benzo[c]furan and Its Derivatives

H. Kwiecień

10.2.1 Product Subclass 1: Benzo[c]furans

The structure and numbering of the parent member of this product class, systematically named benzo[c]furan, are presented in ▶ Scheme 1. The ring system has also been named (with the same atom numbering) as isobenzofuran and 2-benzofuran. Chemical Abstracts uses the isobenzofuran name for 1; however, the systematic name is used as well. In the earlier literature, the skeleton was called 2-benzofurane.

Scheme 1 Structure and Ring Numbering of Benzo[c]furan

There are no known naturally occurring compounds of the fully unsaturated ring system. The first synthesis of a stable benzo[c]furan, 1,3-diphenylbenzo[c]furan (2) (▶ Scheme 2), was reported in 1906.[1] The unstable parent compound 1 has been known since 1964, when its existence as a transient intermediate was first established by trapping it with a reactive dienophile and isolation as the Diels–Alder adduct.[2,3] In later work (1971), the elusive pure benzo[c]furan (1) was isolated and characterized.[4,5] Since that time, a wide variety of benzo[c]furan-related analogues substituted at the furan and/or benzene rings, as well as various annulated homologues of the parent compound, have been prepared. These benzo[c]furans are valuable substrates or intermediates for the synthesis of more complex molecules, which can be useful products for technical and biomedical applications. Some representative examples of such benzo[c]furans are given below.

The parent benzo[c]furan (1), a very reactive molecule, can be used as a precursor monomer for the preparation of polymeric thin films. The optical properties and surface-dependent growth characteristics of the poly(benzo[c]furan) obtained by chemical vapor deposition techniques can provide potential optical (such as components of optical waveguides) and microfluidic applications.[6] 4,7-Dimethoxybenzo[c]furan (3), isolated as a moderately stable crystalline solid, can be used in the synthesis of the anthra-9,10-quinone scaffold of the natural antitumor antibiotic dynemicin A (8) (▶ Scheme 3).[7,8] Diels–Alder reaction of the same benzo[c]furan, as well as its 4,5,7- and 4,6,7-analogues, is a key step in the total synthesis of racemic halenaquinone and racemic xestoquinones (12b-methyl-2,3-dihydro-1H-tetrapheno[5,4-bc]furan-6,8,11(12bH)-triones).[9,10] These pentacyclic marine quinones, which are isolated from tropical sponges, have significant and potentially valuable pharmacological properties and are powerful irreversible inhibitors of some cytoplasmic and receptor protein tyrosine kinases.

Scheme 2 Structures of Benzo[c]furans for Biomedical Applications[7–16]

Scheme 3 4,7-Dimethoxybenzo[c]furan in the Synthesis of Dynemicin A[7]

Other stable aryl- and methoxy-substituted benzo[c]furans (e.g., 4 and 5) can be used in the synthesis of natural lignans.[11,12] For example, 4,5,6-trimethoxy-1-(2,3,4-trimethoxyphenyl)benzo[c]furan (4) is the essential intermediate in the synthesis of racemic lirionol, a tetracyclic bridged natural lignin.[11] Benzo[c]furans bearing an aryl substituent at the C1 position are intermediates in the synthesis of diastereomeric switch molecules for the preparation of α-seleno esters that are used as precursors to farnesyltransferase inhibitors.[13]

1,3-Diphenylbenzo[c]furan (2) is known to be the most efficient agent for trapping singlet oxygen (1O2) and it and its derivatives have been employed in pharmacological studies.[14,15] For example, water-soluble derivatives of 1,3-diphenylbenzo[c]furan such as dyes 6 and 7 can be used as fluorescent scavengers for the detection of singlet oxygen in live mammalian cells (▶ Scheme 2).[14] Such dye scavengers decompose upon reaction with singlet oxygen and this is manifested as a decrease in the fluorescence intensity. The application of singlet oxygen in this context represents the first example of the formation of a cytotoxic drug (singlet oxygen) from a nontoxic prodrug (triplet oxygen) as a result of the chemical reaction of triplet oxygen with a specific endogenous ribonucleic acid in live mammalian cells.[16]

Benzo[c]furans such as 5,6- and 1,3-bis(trimethylsilyl)benzo[c]furans 9 and 10 (▶ Scheme 4) are well-known as isolable versatile building blocks for the synthesis of polycyclic linear hydrocarbons, namely acenes.[17–20] Acenes have been the subject of extensive studies owing to their potential applications in organic electronics. An example of acene synthesis from benzo[c]furan 9 via a Diels–Alder intermediate adduct is given in ▶ Scheme 5.[20] The stable, commercially available 1,3-diphenylbenzo[c]furan (2),[21] 4,7-dimethoxy-1,3-diphenylbenzo[c]furan (5),[22] and 4,9-bis[4-(trifluoromethyl)phenyl]naphtho[2,3-c]furan (11),[23] as well as annulated homologues of 1 such as naphtho[2,3-c]furan (12)[24] and naphtho[1,2-c]furan (13)[25] can also be used in the synthesis of various acenes.[23]

Scheme 4 Benzo[c]furans as Building Blocks for Polycyclic Hydrocarbons (Acenes)[17–25]

Scheme 5 5,6-Bis(trimethylsilyl)benzo[c]furan in the Synthesis of an Anthracene[20]

There are a few examples known of benzo[c]furans in which two furan units are fused to a common aromatic ring: the two benzo[c]difurans 14[26] and 15,[27] the two isomeric naphthodifurans 16[26] and 17,[28,29] and an example in which the furans are fused to opposite faces of a pyrene structure 18 (▶ Scheme 6).[30] These compounds and related examples have been used to prepare π-molecular switches,[31,32] linear polycyclic hydrocarbons,[27,32] and cyclophanes.[30,33] The in situ prepared (Diels–Alder) linear dibenzo[c]furan 19, for which a stable classical valence bond structure cannot be drawn (similar to 15), is a useful monomer for the synthesis of fullerene-type macromolecules.[34] Benzo[c]furan 20 is the only known molecule that contains three furan moieties, and with three sites available for Diels–Alder reactions, it is a potentially useful substrate for the synthesis of polymers and cyclophanes.[26]

Scheme 6 Structure of Benzo[c]furans as Useful Substrates for the Synthesis of Cyclophanes and Fullerenes[26–34]

Scheme 7 Benzo[c]furans for Organic Light-Emitting Devices[39–42]

Because of their importance in synthetic organic chemistry, benzo[c]furans have been reviewed several times.[43–48] A comprehensive review of this product class was included in Houben–Weyl, Vol. E 6b/1, pp 163–216 (1994).

Benzo[c]furan is a Hückel aromatic 10-π species. Its structure can be represented as neutral oxygen-bridged ortho-quinodimethane 1 and mesomeric dipolar canonical forms 25 (▶ Scheme 8).

Scheme 8 Neutral Oxygen-Bridged ortho-Quinodimethane Structure and Mesomeric Dipolar Canonical Form of Benzo[c]furan

Although benzo[c]furan is a 10-π electronic system, the molecule does not possess the usual physical criteria of aromaticity. The aromaticity can be inferred on the basis of energetic (aromatic stabilization), geometric (aromatic bond length equalization), and magnetic properties (1H NMR chemical shifts or magnetic susceptibility exaltation and anisotropy). The resonance energy and nonalternating bond lengths of benzo[c]furan agree almost exactly with the experimentally observed instability and well-known diene character, which reveals itself in the high reactivity toward typical dienophiles. However, these observations disagree with the low-field 1H resonance in its NMR spectrum, which had been considered indicative of a ring current.[4] Because of these contradictions, several theoretical studies, based on the numerous methods for the measurement of the extent of aromaticity, have been performed for the parent benzo[c]furan and its substituted derivatives,[44,47,49–55] and a comparison has been made with the isomeric benzo[b]furan (26). A number of theoretical studies have suggested that the resonance stabilization and aromaticity of benzo[c]furan (1) is smaller than that of benzo[b]furan (26). A very simple HMO (Hückel molecular orbital) method for the determination of resonance energies per π-electron (REPE) in conjugated systems (and its modifications) has shown that the total energy of benzo[c]furan is lower than that of the benzo[b]furan isomer.[49–52] Thus, the REPE values for benzo[c]furan and benzo[b]furan are 0.002 β and 0.036 β, respectively.[50,51] Significant differences in resonance energy (ER) have been obtained for the two isomeric benzofurans from nonempirical calculations (a value of 30.3 kcal•mol–1 for benzo[c]furan, compared with 56.0 kcal•mol–1 for benzo[b]furan).[52]

Density functional theory calculations have been applied to the geometry of benzo[c]furan and its derivatives.[47,54,55] Calculated values for bond lengths (in Å) and the C—O—C angle for benzo[c]furan are given in ▶ Scheme 9 (left).

Scheme 9 Geometric Structure of Benzo[c]furan, and Nucleus-Independent Chemical Shift Values of Benzo[c]furan and Benzo[b]furan[55]

Geometric structures of the stable, crystalline benzo[c]furans 1,3-diphenyl-(2), 4,7-dimethoxybenzo[c]furan (3), and 5,6-(methylenedioxy)benzo[c]furan-1-carbonitrile (27) have been experimentally determined (▶ Scheme 10, bond lengths in Å).[60–62] The geometry of these compounds is close to that calculated for the parent compound.

Scheme 10 Experimentally Determined Structures of 1,3-Diphenylbenzo[c]furan, 4,7-Dimethoxybenzo[c]furan, and 5,6-(Methylenedioxy)benzo[c]furan-1-carbonitrile[60–62]

For 5,6-(methylenedioxy)benzo[c]furan-1-carbonitrile (27), comparison of the experimentally determined bond lengths O-C6-C7-C7a-C1 with O-C5-C4-C3a-C3 (the “bottom” side of 27, with the “top” side as drawn) shows that there is a slight mesomeric interaction between the oxygen atom at C6 and the cyano group at C1, as expressed in dipolar structure 28 (▶ Scheme 11).[62]

Scheme 11 Mesomeric Forms of 5,6-(Methylenedioxy)benzo[c]furan-1-carbonitrile[62]

Benzo[c [furan (1) is a very reactive compound that spontaneously reacts with typical dienophiles such as maleic anhydride, N-phenylmaleimide, and ketones,[63] including 3-acetyloxazol-2(3H)-one,[64] 1,3-diacetylimidazolin-2-one,[64] and azulene-1,7-diones,[65] to give the corresponding cycloadducts. As mentioned above, the ability of the parent compound 1 and its homologues, as well as alkyl-substituted derivatives, to act as dienes in Diels–Alder reactions has led to their wide exploitation as synthetic intermediates to give more complex structures. A number of studies on both computational and experimental aspects of the Diels–Alder reaction of benzo[c]furans have been performed. The reactivity of benzo[c]furan and its 1,3-disubstituted derivatives in Diels–Alder reactions with acetylene, ethene, and cyclopropene,[66] as well as with strong dienophiles such as maleic anhydride,[67] has been evaluated on the basis of frontier molecular orbital energy using AM1 semiempirical methods.[66,67] The transition-state energies assessed by density functional theory calculated for the reaction of benzo[c]furan and its benzannulated homologues as dienes in Diels–Alder reactions with ethene show a linear correlation between activation energies and structure, and indicate a decrease in aromaticity going from benzo[c]furan (1) to anthra[2,3-c]furan.[68] Reaction of benzo[c]furan (1) with bicyclic alkenes such as norbornene leads to the formation of stereoisomeric adduct mixtures (exo and endo),[69,70] whereas the reaction of 1,3-diphenylbenzo[c]furan (2) with norbornene or norbornadiene forms a single stereoisomer.[71] In a similar way, 1,3-diphenylbenzo[c]furan reacts with 7-oxanorbornenes, giving only a single isomer.[72] The use of phenyl substituents to control the stereochemistry in benzo[c]furan cycloadditions opens the way for the synthesis of complex polyalicyclic nanostructures.[72] The reaction of 1,3-diphenylbenzo[c]furan (2) with 3-methylene-1-phenylpyrrolidine-2,5-dione (29) gives a single diastereomer 30 as the result of the stereoselective [4 + 2] cycloaddition (▶ Scheme 12).[73]

Scheme 12 Reaction of 1,3-Diphenylbenzo[c]furan with 3-Methylene-1-phenylpyrrolidine-2,5-dione[73]

Highly reactive 3-(pent-4-enylamino)benzo[c]furan-1-carboxylates [e.g., 32, generated in situ from 6-methoxy-1H-2-benzopyran-1,3(4H)-dione (31)] undergo intramolecular cyclo-additions giving a simple route for the preparation of polycyclic aza compounds (e.g., 33) (▶ Scheme 13).[74]

Scheme 13 Intramolecular Cycloaddition of a 3-Aminobenzo[c]furan-1-carboxylate Derivative[74]

Benzo[c]furan (1) and 4,7-dimethoxybenzo[c]furan (3) react easily with alkynyl chromium(0) Fischer carbenes giving, in one pot, a two-step synthesis of substituted anthraquinones.[75]

As discussed above, the reactivity of benzo[c]furan (1) and 1,3-diphenylbenzo[c]furan (2) with singlet oxygen is well-known. The rate constants of such photooxidation reactions can be related to the ionization of the acceptor and increase in the order furan, benzo[c]furan, 1,3-diphenylbenzo[c]furan (2).[76] Stable 1,3-diphenylbenzo[c]furan (2) is very susceptible to autoxidation at 30°C in tert-butylbenzene containing 2,2′-azobisisobutyronitrile, and it absorbs molecular oxygen to give a mixture of polyperoxide 35 (50%) and 1,2-dibenzoylbenzene (36, 35%) (▶ Scheme 14).[77] A solution of 1,3-diphenylbenzo[c]furan does not absorb oxygen in the dark in the absence of a free-radical initiator at 30°C. Photooxidation of benzo[c]furan 2 with singlet oxygen (1O2) in aromatic solvents gives a monomeric endoperoxide 34 along with minor amounts of 1,2-dibenzoylbenzene [1,2-bis(phenylmethanone)phenylene], whereas in carbon tetrachloride, 1,2-dibenzoylbenzene is the main reaction product.[77]

Scheme 14 Auto- and Photooxidation of 1,3-Diphenylbenzo[c]furan[77]

4,5,7-Tri-tert-butylbenzo[c]furan (37), which is a stable and electronically unperturbed derivative of benzo[c]furan, gives 2,3,5-tri-tert-butylbicyclo[4.1.0]hepta-1(6),2,4-triene-7-carbaldehyde (38) as a primary product when subjected to photolysis at −15°C using a high-pressure mercury lamp (▶ Scheme 15).[78]

Scheme 15 Photolysis of 4,5,7-Tri-tert-butylbenzo[c]furan[78]

UV irradiation of a degassed solution of benzo[c]furan in acetone at −60°C leads to the formation of a crystalline [8 + 8] dimeric anti-isomer 40 (mp 234–236°C), whereas in diethyl ether solution an [8 + 4] unsymmetrical dimer 39 is obtained (mp 130–131°C) (▶ Scheme 16).[79,80] Lanthanide-induced shift spectroscopy allows the determination of the stereochemistry of this process.

Scheme 16 UV Irradiation of Benzo[c]furan[79,80]

Oxidation of 1,3-disubstituted benzo[c]furans (e.g., 41) with activated manganese(IV) oxide in dichloromethane at room temperature leads to furan ring opening, giving 1,2-di(het)aroylbenzenes (e.g., 42) in good yields (▶ Scheme 17).[81] Lead(IV) acetate mediated oxidative cleavage of 1,3-diaryl- and 1,3-dihetarylbenzo[c]furan derivatives in tetrahydrofuran at 50°C also leads to the corresponding diketones.[82]

Scheme 17 Oxidation of 1,3-Di(thien-2-yl)benzo[c]furan with Manganese(IV) Oxide[81]

1,3-Diphenylbenzo[c]furan (2) in tetrahydrofuran easily undergoes reductive metalation with lithium, sodium, or potassium to form a deep blue solution of a dianion (e.g., 43), which easily undergoes protonation, methylation, or carboxylation to give two stereoisomers of the corresponding 1,3-diphenyl-1,3-dihydrobenzo[c]furans 44. In each case, the major isomer is the cis-product. The stereoselective preference for the cis-product seems to be the result of an adoption of a preferred conformation by the dianion in which steric interaction between phenyl substituents is minimized (▶ Scheme 18).[83]

Scheme 18 Formation and Reactivity of 1,3-Diphenylbenzo[c]furan Dianion[83]

Electrophile

E

Yield (%)

Ref

HCl

H

80

[

83

]

MeI

Me

11

[

83

]

CO

2

CO

2

H

72

[

83

]

The hypothesis that the dianion reacts in a stereoselective cis manner has been supported by similar behavior of the monoanion formed by reductive metalation of 1-tert-butyl-3-phenylbenzo[c]furan.[84] Electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) studies of ion pairs from various substituted 1,3-diarylbenzo[c]furans and alkali metals have shown that the lifetime of the radical anions increases in the order of decreasing electron spin density and excess negative charge on the furan ring.[85]

Theoretical prediction of the acidities (pKa) of C—H bonds of five-membered aromatic benzoheterocyclic compounds in dimethyl sulfoxide solution, including benzo[c]furan, has been carried out.[86] These calculations could be useful for predicting the functionalization of such heterocyclic scaffolds, especially dehydromethylation reactions. The pKa values for benzo[c]furan (1) and benzo[b]furan (26) are shown in ▶ Scheme 19.

Scheme 19 Calculated pKa Values for Benzo[c]furan and Benzo[b]furan[86]

Benzo[c]furan can also be obtained as a solution in benzene upon oxidative methoxylation of commercially available phthalane, under a nitrogen atmosphere at room temperature and subsequent 1,4-elimination with lithium diisopropylamide.[87,88] After careful evaporation of benzene, benzo[c]furan can be purified by column chromatography over silica gel and isolated as a colorless solid with a yield of 66%. In crystalline form, the compound is stable for eight months at −15°C without decomposition (polymerization).[88]

1-Methylbenzo[c]furan (45) and 1,3-dimethylbenzo[c]furan, which can also be synthesized by flash thermolysis of the corresponding 1,2,3,4-tetrahydro-1,4-epoxynaphthalenes, decompose quickly in solution at room temperature; the presence of triethylamine retards this decomposition somewhat. A spectroscopic study of the two compounds indicates the existence of a tautomeric equilibrium between them and their corresponding 1-methylene-1,3-dihydrobenzo[c]furan isomers (e.g., 46) (▶ Scheme 20).[91] It was also found that the phenyl substituent plays an important role in the tautomeric equilibrium: in the case of 1-benzylbenzo[c]furan (47), the tautomer 48 is more stable than 47.[91]

Scheme 20 Tautomeric Isomers of 1-Methyl- and 1-Benzylbenzo[c]furan[91]

Although benzo[c]furan itself and its alkyl derivatives and homologues are reactive, and as a result are difficult to isolate at room temperature, there are a number of derivatives bearing electron-withdrawing groups (e.g., a cyano group)[62] on the furan or benzene ring, or a bulky group such as an aryl[92] or tert-butyl[78] substituent at the C1 and C3 position that provide increased stability so that the compounds can be isolated as crystalline solids. Additionally, stability has been achieved by linking through the 1,3-positions and incorporation into alicyclophanes (e.g., as in 49), where the benzo[c]furan moiety is sterically shielded from reaction (▶ Scheme 21).[93]

Scheme 21 A Stable Benzo[c]furan Alicyclophane Macrocycle[93]

The spectroscopic properties of several benzo[c]furans are given below.

Benzo[c]furan (1): UV (cyclohexane) λmax: 215, 244, 249, 254, 261, 292, 305, 313, 319, 327, 334, 343 nm;[86] 1H NMR (CCl4, δ): 6.70 (s, 2H), 7.22 (s, 2H), 7.80 (s, 2H).[63]

5,6-(Methylenedioxy)benzo[c]furan-1-carbonitrile (27): UV (MeOH) λmax (log ∊): 316 (3.3) nm; IR (CHCl3) ṽmax: 2211 cm–1; 1H NMR (80 MHz, CDCl3, δ): 5.99 (s, 2H, OCH2O), 6.71, 6.73 (s, 1H each H-4 and H-7), 7.86 (s, 1H, H-3).[62]

4,5,7-Tri-tert-butylbenzo[c]furan (37): UV (MeCN) λmax (log ∊): 217 (4.5), 332 (∊ 3.7) nm; IR (KBr) ṽmax: 2940, 1595, 1075, 885, 845, 740 cm–1; 1H NMR (CD3CN, δ): 1.38 (s, 9H), 1.46 (s, 9H), 1.60 (s, 9H), 6.88 (s, 1H), 8.05 (d, 1H), 8.13 (d, 1H).[78]

1-Methylbenzo[c]furan (45): UV (heptane) λmax: 207, 236, 244, 251, 270, 282, 291, 309, 317, 324, 332, 340, 347, 357 nm; 1H NMR (CDCl3, δ): 2.56 (s, 3H, CH3), 6.59–6.81 (m, 2H, Ar), 7.06–7.21 (m, 2H, Ar), 7.74 (s, 1H, Ar).[91]

10.2.1.1 Synthesis by Ring-Closure Reactions

10.2.1.1.1 Annulation to an Arene

10.2.1.1.1.1 Formation of One O—C and One C—C Bond

10.2.1.1.1.1.1 Method 1: From Aromatic Ketimines and Aldehydes by Rhenium Catalysis

The strategy of such syntheses of benzo[c]furans requires two key processes: C—H bond activation and introduction of an oxygen atom into the starting aromatic unsaturated species such as a ketimine. Ruthenium and rhodium complexes have been commonly used for C—H bond activation, usually followed by the insertion of nonpolar unsaturated molecules such as alkenes and acetylenes. On the other hand, the insertion of a polar molecule, such as an aldehyde, into the metal—carbon bonds derived from C—H bond activation can be achieved using rhenium complexes. Rhenium has lower electronegativity than either ruthenium or rhodium, therefore a carbon—rhenium bond is more polarized than a carbon—ruthenium or carbon—rhodium bond, which should ensure that the organorhenium species reacts successfully with aldehydes in the manner of a Grignard reagent. Thus, the insertion of aldehydes into the C—H bond of aromatic unsaturated species such as ketimines can provide benzo[c]furans via further intramolecular nucleophilic cyclization.[94]

Scheme 22 Synthesis of Benzo[c]furans by Rhenium-Catalyzed Reaction of Aromatic Ketimines with Aldehydes[94,95]

R

1

R

2

R

3

Yield (%)

Ref

Ph

Ph

Ph

93

[

94

]

Ph

Bn

Ph

91

[

94

]

(

E

)-CH=CHPh

Ph

Ph

79

[

94

]

Ph

Ph

4-MeOC

6

H

4

70

[

94

]

Ph

Ph

4-Tol

91

[

94

]

Ph

Ph

4-F

3

CC

6

H

4

93

[

94

]

Ph

Ph

2-Tol

86

[

94

]

Ph

Ph

(

E

)-CH=CHPh

78

[

94

]

Ph

Ph

4-[Me(CH

2

)

9

O]C

6

H

4

68

[

95

]

Ph

Ph

4-MeO

2

CC

6

H

4

97

[

95

]

Ph

Ph

88

[

95

]

Ph

Ph

2-thienyl

99

[

95

]

The proposed reaction mechanism for this synthesis of benzo[c