Isocyanide Chemistry E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 872

Veröffentlichungsjahr: 2012

Beschreibung

The efficacy of isocyanide reactions in the synthesis of natural or naturallike products has resulted in a renaissance of isocyanide chemistry. Now isocyanides are widely used in different branches of organic, inorganic, coordination, combinatorial and medicinal chemistry.

This invaluable reference is the only book to cover the topic in such depth, presenting all aspects of synthetic isonitrile chemistry. The highly
experienced and internationally renowned editor has brought together an equally distinguished team of authors who cover multicomponent
reactions, isonitriles in total synthesis, isonitriles in polymer chemistry and much more.

Leseprobe

Table of Contents

Cover

Related Titles

Title page

Copyright page

Preface

List of Contributors

1 Chiral Nonracemic Isocyanides

1.1 Introduction

1.2 Simple Unfunctionalized Isocyanides

1.3 Isocyanides Containing Carboxylic, Sulfonyl, or Phosphonyl Groups

1.4 Isocyanides Containing Amino or Alcoholic Functionalities

1.5 Natural Isocyanides

1.6 Isocyanides Used in the Synthesis of Chiral Polyisocyanides

2 General Aspects of Isocyanide Reactivity

2.1 Introduction

2.2 Isocyanide–Cyanide Rearrangement

2.3 Oxidation/Reduction of the Isocyano Group

2.4 Reactions of Isocyanides with Electrophiles

2.5 Reactions of Isocyanides with Nucleophiles

2.6 Conclusions

3 α-Acidic Isocyanides in Multicomponent Chemistry

3.1 Introduction

3.2 Synthesis of α-Acidic Isocyanides

3.3 Reactivity of α-Acidic Isocyanides

3.4 MCRs Involving α-Acidic Isocyanides

3.5 Conclusions

4 Synthetic Application of Isocyanoacetic Acid Derivatives

4.1 Introduction

4.2 Synthesis of α-Isocyanoacetate Derivatives

4.3 Alkylation of Isocyanoacetic Acid Derivatives

4.4 α-Isocyanoacetates as Michael Donors

4.5 Reaction of Isocyanoacetic Acids with Alkynes: Synthesis of Pyrroles

4.6 Reaction of Isocyanoacetic Acid Derivatives with Carbonyl Compounds and Imines

4.7 Reaction with Acylating Agents

4.8 Multicomponent Reactions of Isocyanoacetic Acid Derivatives

4.9 Chemistry of Isocyanoacetates Bearing an Additional Functional Group

4.10 Reactions of Isocyanoacetic Acids with Sulfur Electrophiles

4.11 Miscellaneous Reactions

4.12 Concluding Remarks

4.13 Notes Added in Proof

5 Ugi and Passerini Reactions with Carboxylic Acid Surrogates

5.1 Introduction

5.2 Carboxylic Acid Surrogates

5.3 Use of Mineral and Lewis Acids

5.4 Conclusions

6 Amine (Imine) Component Surrogates in the Ugi Reaction and Related Isocyanide-Based Multicomponent Reactions

6.1 Introduction

6.2 Hydroxylamine Components in the Ugi Reaction

6.3 Hydrazine Components in the Ugi Reaction

6.4 Miscellaneous Amine Surrogates for the Ugi Reaction

6.5 Activated Azines in Reactions with Isocyanides

6.6 Enamines, Masked Imines, and Cyclic Imines in the Ugi Reaction

6.7 Concluding Remarks

Acknowledgments

7 Multiple Multicomponent Reactions with Isocyanides

7.1 Introduction

7.2 One-Pot Multiple IMCRs

7.3 Isocyanide-Based Multiple Multicomponent Macrocyclizations

7.4 Sequential Isocyanide-Based MCRs

7.5 Conclusions

8 Zwitterions and Zwitterion-Trapping Agents in Isocyanide Chemistry

8.1 Introduction

8.2 Generation of Zwitterionic Species by the Addition of Isocyanides to Alkynes

8.3 Generation of Zwitterionic Species by the Addition of Isocyanides to Arynes

8.4 Generation of Zwitterionic Species by the Addition of Isocyanides to Electron-Deficient Olefins

8.5 Miscellaneous Reports for the Generation of Zwitterionic Species

8.6 Isocyanides as Zwitterion-Trapping Agents

8.7 Conclusions

Acknowledgments

9 Recent Progress in Nonclassical Isocyanide-Based MCRs

9.1 Introduction

9.2 Type I MCRs: Isocyanide Attack on Activated Species

9.3 Type II MCRs: Isocyanide Activation

9.4 Type III MCRs: Formal Isocyanide Insertion Processes

9.5 Conclusions

Acknowledgments

10 Applications of Isocyanides in IMCRs for the Rapid Generation of Molecular Diversity

10.1 Introduction

10.2 Ugi/Deprotect/Cyclize (UDC) Methodology

10.3 Secondary Reactions of Ugi Products

10.4 The Bifunctional Approach (BIFA)

Acknowledgments

11 Synthesis of Pyrroles and Their Derivatives from Isocyanides

11.1 Introduction

11.2 Synthesis of Pyrroles Using TosMIC

11.3 Synthesis of Pyrroles Using Isocyanoacetates

11.4 Synthesis of Porphyrins and Related Compounds

11.5 Conclusion

12 Isocyanide-Based Multicomponent Reactions towards Benzodiazepines

12.1 Introduction

12.2 1,4-Benzodiazepine Scaffolds Assembled via IMCR Chemistry

12.3 1,5-Benzodiazepine Scaffolds Assembled via IMCR Chemistry

12.4 Outlook

13 Applications of Isocyanides in the Synthesis of Heterocycles

13.1 Introduction

13.2 Furans

13.3 Pyrroles

13.4 Oxazoles

13.5 Isoxazoles

13.6 Thiazoles

13.7 Imidazoles

13.8 Pyrazoles

13.9 Oxadiazoles and Triazoles

13.10 Tetrazoles

13.11 Benzofurans and Benzimidazoles

13.12 Indoles

13.13 Quinolines

13.14 Quinoxaline

14 Renaissance of Isocyanoarenes as Ligands in Low-Valent Organometallics

14.1 Historical Perspective

14.2 Isocyanidemetalates and Related Low-Valent Complexes

14.3 Coordination and Surface Chemistry of Nonbenzenoid Isocyanoarenes

14.4 Conclusions and Outlook

Acknowledgments

15 Carbene Complexes Derived from Metal-Bound Isocyanides: Recent Advances

15.1 Introduction

15.2 Coupling of the Isocyanide Ligand with Simple Amines or Alcohols

15.3 Coupling of the Isocyanide Ligand with Functionalized Amines or Alcohols

15.4 Coupling of the Isocyanide Ligand with a Hydrazine or Hydrazone

15.5 Coupling of the Isocyanide Ligand with an Imine or Amidine

15.6 Intramolecular Cyclizations of Functionalized Isocyanide Ligands

15.7 Coupling of Isocyanides with Dipoles

15.8 Other Reactions

15.9 Final Remarks

Acknowledgments

16 Polyisocyanides

16.1 Introduction

16.2 The Polymerization Mechanism

16.3 Conformation of the Polymeric Backbone

16.4 Polyisocyanopeptides

16.5 Polyisocyanides as Scaffolds for the Anchoring of Chromophoric Molecules

16.6 Functional Polyisocyanides

16.7 Conclusions and Outlook

Index

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E-Book

ISBN: 978-0-470-62653-5

The Editor

Prof. Dr. Valentine G. Nenajdenko

Moscow State University

Leninskie Gory

119992 Moscow

Russia

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

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

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The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.

© 2012 Wiley-VCH Verlag & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

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Preface

Isocyanide (isonitrile) chemistry began in 1859 when Lieke obtained the first compound of this type. In 1958, isocyanides became generally available by dehydration of formamides prepared from primary amines. This discovery and many other important inventions in the chemistry of isocyanides have been attributed to Ivar Ugi. He was probably the first person to understand the exceptional nature of isocyano functionality and its rich synthetic possibilities. Being stable carbenes, isonitriles are highly reactive compounds that can react with almost any type of reagents (electrophiles, nucleophiles and even radicals). Today isocyanide chemistry is a broad and important part of organic chemistry; however inorganic, coordina­tion, polymeric, combinatorial and medicinal chemistry explore the rich reactivity of isonitriles as well. Multicomponent reactions with isocyanides are used for synthesis of broad varieties of peptides and peptide mimetics. The renaissance of isocyanide chemistry was at the end of the 20th century when thousands of new compounds libraries became highly desirable for diversity-oriented synthesis, high-throughput screening and drug discovery. Isocyanide-based multicomponent reactions are out of competition in terms of effectiveness and economy to synthesize drugs like compounds or natural compounds only in a single synthetic step.

In this book, an effort has been made to provide a comprehensive modern view of all the most significant branches of isocyanide chemistry, demonstrating how important are these compounds to date and how significant is their impact on chemistry. It should be pointed out that the book Isonitrile Chemistry was published by Ivar Ugi in 1971. Since then a number of excellent reviews and monograph chapters regarding isocyanides, in particular their multicomponent reactions, have been published. However, a book devoted to the chemistry of isocyanides has not been published for more than 40 years.

It is a great honor and pleasure for me to be the editor of this book. I would like to thank all the authors of the individual chapters for their excellent contributions. These outstanding scientists are known experts in the field of isocyanide chemistry. This book is a result of worldwide cooperation of contributors from many countries. I would like also to thank all my collaborators at Wiley-VCH for help to realize this project.

I also wish to use this opportunity to mention my personal love for isocyanide chemistry. Almost 25 years ago as a student, I read Isonitrile Chemistry by Ivar Ugi. Such a beautiful and rich chemistry made me dream to do something important and interesting in this field. However, it was impossible at that time because I was still a student. Nevertheless, I synthesized my first isocyanide and had experience with specific odors of isonitriles. My next step to isocyanides was the conference in Yaroslavl, Russia, in 2001, where I met Ivar Ugi. We had a long and fruitful discussion, and this talk supported me significantly. Since then my laboratory has been involved in isocyanide chemistry. I would like to dedicate this book to the memory of an outstanding chemist and major pioneer of isocyanide chemistry, Ivar Ugi.

Valentine G. NenajdenkoMoscow, 2012

List of Contributors

Niels AkeroydRadboud University NijmegenInstitute for Molecules and MaterialsHeyendaalseweg 1356525 AJ NijmegenThe Netherlands

Irini Akritopoulou-ZanzeAbbott LaboratoriesScaffold-Oriented SynthesisAbbott Park, IL 60064USA

Muhammad AyazThe University of ArizonaCollege of PharmacyBIO5 Oro ValleyTucson, AZ 85737USA

Luca BanfiUniversità a degli Studi di GenovaDipartimento di Chimica e Chimica IndustrialeVia Dodecaneso 3116146 GenovaItaly

Mikhail V. BarybinThe University of KansasDepartment of Chemistry1251 Wescoe Hall DriveLawrence, KS 66045USA

Andrea BassoUniversità a degli Studi di GenovaDipartimento di Chimica e Chimica IndustrialeVia Dodecaneso 3116146 GenovaItaly

Fabio De MolinervThe University of ArizonaCollege of PharmacyBIO5 Oro ValleyTucson, AZ 85737USA

Justin DietrichvThe University of ArizonaCollege of PharmacyBIO5 Oro ValleyTucson, AZ 85737USA

Alexander DömlingUniversity of PittsburghSchool of PharmacyDepartment of Pharmaceutical SciencesPittsburgh, PA 15261USA

Laurent El KaïmEcole Nationale Supérieure des Techniques AvancéesUnité Chimie et ProcédésUMR 7652CNRS-ENSTA-Polytechnique32 Bd Victor75012 ParisFrance

Niels EldersVU University AmsterdamDepartment of Chemistry & Pharmaceutical SciencesDe Boelelaan 10831081 HV AmsterdamThe Netherlands

Laurence GrimaudEcole Nationale Supérieure des Techniques AvancéesUnité Chimie et ProcédésUMR 7652CNRS-ENSTA-Polytechnique32 Bd Victor75012 ParisFrance

Anton V. GulevichMoscow State UniversityDepartment of ChemistryLeninskie GoryMoscow 119991Russia

Yijun HuangUniversity of PittsburghSchool of PharmacyDepartment of Pharmaceutical SciencesPittsburgh, PA 15261USA

Christopher HulmeThe University of ArizonaCollege of PharmacyBIO5 Oro ValleyTucson, AZ 85737USA

Nicola KiellandBarcelona Science ParkUniversity of BarcelonaBaldiri Reixac 10-1208028 BarcelonaSpain

Mikhail KrasavinGriffith UniversityEskitis InstituteBrisbane, QLD 4111Australia

Rodolfo LavillaBarcelona Science ParkUniversity of BarcelonaBaldiri Reixac 10-1208028 BarcelonaSpain

Konstantin V. LuzyaninTechnical University of LisbonCentro de Química EstruturalInstituto Superior Técnico1049-001 LisbonPortugal

Ali MalekiIran University of Science and TechnologyDepartment of ChemistryNarmakTehran 16846-13114Iran

John J. Meyers, JrThe University of KansasDepartment of Chemistry1251 Wescoe Hall DriveLawrence, KS 66045USA

Maxim A. MironovvUral Federal UniversityDepartment of Technology for Organic Synthesisstr. Mira, 19620002 EkaterinburgRussia

Brad M. NealThe University of KansasDepartment of Chemistry1251 Wescoe Hall DriveLawrence, KS 66045USA

Valentine G. NenajdenkovMoscow State UniversityDepartment of ChemistryLeninskie Gory119991 MoscowRussia

Ricardo A.W. Neves FilhoLeibniz Institute of Plant BiochemistryDepartment of Bioorganic ChemistryWeinberg 306120 Halle (Saale)Germany

Roeland J.M. NolteRadboud University NijmegenInstitute for Molecules and MaterialsHeyendaalseweg 1356525 AJ NijmegenThe Netherlands

Tetsuo OkujimaEhime UniversityGraduate School of Science and EngineeringDepartment of Chemistry and Biology2-5 Bunkyo-choMatsuyama 790-8577Japan

Noboru OnoKyoto UniversityInstitute for Integrated Cell-Material Sciences (iCeMS)Nishikyo-kuKyoto 615-8510Japan

Romano V.A. OrruVrije Universiteit AmsterdamDepartment of Chemistry and Pharmaceutical SciencesDe Boelelaan 10831081 HV AmsterdamThe Netherlands

Armando J.L. PombeiroTechnical University of LisbonCentro de Química EstruturalInstituto Superior Técnico1049-001 LisbonPortugal

Rosario RamónBarcelona Science ParkUniversity of BarcelonaBaldiri Reixac 10-1208028 BarcelonaSpain

Renata RivaUniversità a degli Studi di GenovaDipartimento di Chimica e Chimica IndustrialeVia Dodecaneso 3116146 GenovaItaly

Daniel G. RiveraLeibniz Institute of Plant BiochemistryDepartment of Bioorganic ChemistryWeinberg 306120 Halle (Saale)GermanyandFaculty of ChemistryUniversity of HavanaCenter for Natural Products StudyZapata y G10400 La HabanaCuba

Alan E. RowanRadboud University NijmegenInstitute for Molecules and MaterialsHeyendaalseweg 1356525 AJ NijmegenThe Netherlands

Eelco RuijterVU University AmsterdamDepartment of Chemistry & Pharmaceutical SciencesDe Boelelaan 10831081 HV AmsterdamThe Netherlands

Afshin SarvaryShahid Beheshti UniversityDepartment of ChemistryG. C. P. O. Box 19396-4716TehranIran

Ahmad ShaabaniShahid Beheshti UniversityDepartment of ChemistryG. C. P. O. Box 19396-4716TehranIran

Ludger A. WessjohannLeibniz Institute of Plant BiochemistryDepartment of Bioorganic ChemistryWeinberg 306120 Halle (Saale)Germany

Alexander G. ZhdankoMoscow State UniversityDepartment of ChemistryLeninskie GoryMoscow 119991Russia

1

Chiral Nonracemic Isocyanides

Luca Banfi, Andrea Basso, and Renata Riva

1.1 Introduction

Although isocyanides have proven to be very useful synthetic intermediates – especially in the field of multicomponent reactions – most research investigations performed to date on isocyanides have involved commercially available, unfunctionalized and achiral (or chiral racemic) compounds. Two reasons can be envisioned for the infrequent use of enantiomerically pure isocyanides: (i) the general lack of asymmetric induction produced by them; and (ii) the high tendency to lose stereochemical integrity in some particular classes of isonitriles. However, it is believed that when these drawbacks are overcome, the use of chiral non-racemic isocyanides in multicomponent reactions can be very precious, allowing a more thorough exploration of diversity (in particular stereochemical diversity) in the final products. Recently, several reports have been made describing the preparation and use of new classes of functionalized chiral isocyanides. In fact, several chiral isocyanides may be found in nature, and these will be briefly described in Section 1.5, with attention focused on their total syntheses. Another growing application of chiral isocyanides is in the synthesis of chiral helical polyisocyanides.

It is hoped that this review will encourage chemists first to synthesize a larger number of chiral isocyanides, and subsequently to exploit them in multicomponent reactions, in total synthesis, and in the material sciences.

1.2 Simple Unfunctionalized Isocyanides

The standard method used to prepare chiral isocyanides (whether functionalized, or not) begins from the corresponding amines, and employs a two-step se­quence of formylation and dehydration (Scheme 1.1). Many enantiomerically pure amines are easily available from natural sources, classical resolution [1], or asymmetric synthesis. Formylation is commonly achieved via four general methods: (i) refluxing the amine in ethyl formate [2]; (ii) reacting the amine with the mixed formic–acetic anhydride [2]; (iii) reacting the amine with formic acid and DCC (dicyclohexylcarbodiimide) [3] or other carbodiimides [4]; and (iv) reacting the amine with an activated formic ester, such as cyanomethyl formate [5], p-nitrophenyl formate [6], or 2,4,5-trichlorophenyl formate [7]. For the dehydration step, several reagents are available, with the commonest and mildest methods involving POCl3, diphosgene, or triphosgene at low temperatures in the presence of a tertiary amine [2]. Although less commonly used, Burgess reagent (methyl N-(triethylammoniumsulfonyl)carbamate) [8] and the CCl4/PPh3/Et3N system [7] have also been employed.

Scheme 1.1

Alternatively, formamides can be obtained from chiral carboxylic acids, through a stereospecific Curtius rearrangement followed by reduction of the resulting isocyanate [9, 10].

Isocyanides may also be prepared from alcohols, by conversion of the alcohol into a sulfonate or halide, followed by SN2 substitution with AgCN [11]; however, this method works well only with primary alcohols. In contrast, a series of chiral isocyanides have been synthesized from chiral secondary alcohols via a two-step protocol that involves conversion first into diphenylphosphinite, followed by a stereospecific substitution that proceeds with a complete inversion of configuration [12]. The substitution step is indeed an oxidation–substitution, that employs dimethyl-1,4-benzoquinone (DMBQ) as a stoichiometric oxidant and ZnO as an additive. Alternatively, primary or secondary alcohols can be converted into formamides through the corresponding alkyl azides and amines.

Some examples of simple chiral isocyanides are shown in Scheme 1.1. These materials have all been prepared in a traditional manner, starting from chiral amines; the exception here is 5, which was synthesized from the secondary alcohol. The compounds comprise fully aliphatic examples such as 1 [13], α-substituted benzyl isocyanides such as 2 [1, 2, 13, 14] and 3 [14, 15], and α-substituted phenethyl or phenylpropyl isocyanides such as 4 [2] and 5 [12].

Because of the great synthetic importance of isocyanide-based multicomponent reactions, these chiral isocyanides have been often used as inputs in these reactions. The use of enantiomerically pure isocyanides can, in principle, bring about two advantages: (i) the possibility to obtain a stereochemically diverse adduct, controlling the absolute configuration of the starting isonitrile; and (ii) the possibility to induce diastereoselection in the multicomponent reaction. With regards to the second of these benefits, the results have been often disappointing, most likely because of the relative unbulkiness of this functional group. For example, Seebach has screened a series of chiral isocyanides, including 2a and 4 in the TiCl4-mediated addition to aldehydes, but with no diastereoselection at all [2]. This behavior seems quite general also for the functionalized isocyanides described later, the only exception known to date being represented by the camphor-derived isocyanide 6 [16], which afforded good levels of diastereoselection in Passerini reactions. The same isonitrile gave no asymmetric induction in the corresponding Ugi reaction, however. Steroidal isocyanides have also been reported (i.e., 7) [17, 18].

Apart from multicomponent reactions, and the synthesis of polyisocyanides (see Section 1.6), chiral unfunctionalized isocyanides have been used as intermediates in the synthesis of chiral nitriles, exploiting the stereospecific (retention) rearrangement of isocyanides into nitriles under flash vacuum pyrolysis conditions (FVP) [14, 19]. This methodology was used for the enantioselective synthesis of the anti-inflammatory drugs ibuprofen and naproxen, from and , respectively. As isocyanides are usually prepared from amines, the overall sequence represents the homologation of an amine to a carboxylic derivative, and is therefore opposite to the Curtius rearrangement.