Chapter 1
Gold-Catalyzed Cyclizations of Alkynes with Alkenes and Arenes

Antonio M. Echavarren, Michael E. Muratore, Verónica López-Carrillo, Ana Escribano-Cuesta, Núria Huguet, and Carla Obradors

Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007, Tarragona, Spain

1. Acknowledgments
2. Introduction
3. Mechanism and Stereochemistry
   1. Structural Considerations of Gold Complexes
   2. General Mechanisms and Stereochemical Aspects
   3. Propargyl Migrations
4. Scope and Limitations
   1. Intermolecular Reactions between Alkynes and Alkenes
   2. Cycloisomerization Reactions
      1. Cycloisomerizations and Skeletal Rearrangements of 1,5-Enynes
      2. Cycloisomerizations and Skeletal Rearrangements of 1,6-Enynes
      3. Cycloisomerizations and Skeletal Rearrangements of 1,7- and Higher Enynes
      4. Cycloisomerizations toward the Formation of Cyclobutenes
      5. Cycloisomerizations of Enamine and Enol-Constituted Enynes
         1. Cycloisomerizations of Enamines
         2. Cycloisomerizations of Enols Formed in Situ by Conia-Ene Reactions
         3. Cycloisomerizations of Enol Ethers
   3. Oxidative Cycloisomerizations of Enynes
   4. Cyclopropanations by the Gold Carbene Intermediates
   5. Cycloisomerizations of Enynes Bearing Propargylic Carboxylates
      1. Cycloisomerizations of Enynes via Propargylic Acyloxy Migration
         1. Migrations on 1,3-Enynes
         2. Migrations on 1,4-Enynes
         3. Migrations on 1,5-Enynes
         4. Migrations on 1,6-Enynes
         5. Migrations on 1,7- and Higher Enynes
   6. Other Isomerizations of Propargylic Derivatives
      1. Cycloisomerizations of Hydroxy- and Alkoxy-Substituted Enynes
         1. Cycloisomerizations of 1,5-Enynes
         2. Cycloisomerizations of 1,6-Enynes
   7. Nucleophilic Additions to 1,n-Enynes
      1. Hydroxy-, Alkoxy-, and Aminocyclizations of Enynes
         1. Additions to 1,5-Enynes
         2. Additions to 1,6-Enynes
         3. Additions to 1,7-Enynes
      2. Additions of Carbon Nucleophiles to Enynes
         1. Additions of Aryl Nucleophiles
         2. Additions of Dicarbonyl Nucleophiles
         3. Additions of Alkenyl Nucleophiles
   8. Cyclizations of Aryl- and Heteroarylalkynes
      1. Cyclizations of Arylalkynes by Friedel-Crafts-Type Processes
      2. Reactions of Indoles with Alkynes
      3. Reactions of Furans with Alkynes
5. Applications to Synthesis
6. Comparison With Other Methods
7. Experimental Conditions
8. Experimental Procedures
   1. Preparation of Gold Complexes
      1. Gold(I) Chloro(tris(2,4-di-tert-butylphenyl)phosphite) [Synthesis of a Phosphite Gold(I) Chloride Complex from NaAuCl4]162
      2. Benzonitrile(tris(2,4-di-tert-butylphenyl)phosphite)gold(I) Hexafluoroantimonate [Synthesis of a Cationic Phosphite Gold(I) Complex]131
      3. Chloro[(2´,4´,6´-triisopropyl-1,1´-biphenyl-2-yl)di-tert-butylphosphine]gold(I), (t-BuXPhos)AuCl [Synthesis of a Phosphine Gold(I) Chloride Complex from (Me2S)AuCl]895
      4. Gold(I) Chloro(1,3-di(2,6-diisopropylphenyl)-2-imidazolidinylidene), (sIPr)AuCl [Synthesis of an NHC Gold(I) Chloride Complex from (Me2S)AuCl]132
      5. Dichloro(2-pyridinecarboxylato)gold(III), PicAuCl2 [Synthesis of a Gold(III) Chloride Complex from NaAuCl4]896, 897
   2. Gold-Catalyzed Alkyne Cyclizations
      1. Dimethyl 3-((Z)-2,6-Dimethylhepta-1,5-dien-1-yl)cyclopent-3-ene-1,1-dicarboxylate [Cycloisomerization of a 1,6-Enyne]225
      2. (3aR*,8aR*)-4-Phenyl-5,6,7,8-tetrahydro-1H-benzo[1,4]cyclobuta[1,2-c]furan-3(3aH)-one [Formation of a Cyclobutene from 1,6- and 1,7-Enynes]425
      3. Triisopropyl((3-methyl-2,5-dihydro-[1,1´-biphenyl]-4-yl)oxy)silane [Cycloisomerization of a 1,5-Enyne]290, 291
      4. (3aR*,5R*,5aS*,5bS*)-2-Tosyloctahydro-3a,5-methanocyclopropa[4´,5´]cyclopenta[1´,2´:1,3]cyclopropa[1,2-c]pyrrole [Intramolecular Cyclopropanation by an Intermediate Enyne-Derived Gold Carbene]506
      5. (5R*,6S*)-1-((1S*,8R*,9S*)-Bicyclo[6.1.0]non-4-en-9-yl)-6-phenyl-3-tosyl-3-azabicyclo[3.1.0]hexane [Intermolecular Cyclopropanation by an Intermediate Enyne-Derived Gold Carbene]510
      6. Dimethyl 3-(1-Ethoxy-1-methylethyl)-4-methylenecyclopentane-1,1-dicarboxylate [Alkoxycyclization of an Enyne]225
      7. Dimethyl (R*)-3-Methylene-4- ((S*)-2-methyltetrahydrofuran-2-yl)cyclopentane-1,1-dicarboxylate [Cycloisomerization of a Hydroxy-Substituted 1,n-Enyne]225
      8. 3-(2-Phenylvinylidene)heptan-1-ol [Intramolecular Addition of an Enol Ether to an Alkyne]615
      9. 1-Benzoyl-2-methylenecyclopentanecarboxylic Acid, Ethyl Ester [Intramolecular Addition of a ß-Keto Ester to an Alkyne]439
      10. (R*)-Dimethyl 3-((R*)-2-Benzoyl-3-oxo-1,3-diphenylpropyl)-4-methylenecyclopentane-1,1- Dicarboxylate [Intermolecular Addition of a ß-Keto Ester to an Alkyne]131
      11. (1R*5S*)-1,3,5-Trimethoxy-2-(2-((1R,5S)-2-methyl-5-(phenylsulfonyl)cyclopent-2-en-1-yl)propan-2-yl)benzene [Intermolecular Addition of an Aryl Nucleophile to a 1,5-Enyne]131
      12. (1R,3aS,4S,7S)-1,2,3,3a,4,5,6,7-Octahydro-1,4-dimethyl-7-(1-methylethyl)-1-(triethylsilyl)oxy-4,7-epoxyazulene [Intramolecular Addition of a Carbonyl Compound to an Alkyne]847
      13. (E)-Dimethyl 3-(2,4,6-Trimethylstyryl)cyclopent-3-ene-1,1-dicarboxylate [Intermolecular Addition of a Carbonyl Compound to an Alkyne]628
      14. 6-Methyl-2H-chromene [Cyclization of an Arylalkyne by a Friedel-Crafts Process]696
      15. (7-Hydroxy-6-methyl-2-((4-nitrophenyl)sulfonyl)isoindolin-5-yl)methyl Pivalate. [Intramolecular Reaction of a Furan with an Alkyne]791
9. Tabular Survey
   1. Chart 1 Phosphorus Ligands Used in Tables
   2. Chart 2 N-Heterocyclic Carbenes Used as Ligands in Tables
   3. Chart 3 Other Ligands Used in Tables
   4. Chart 4 Chiral Ligands Used in Tables
   5. Chart 5 Gold(I) Complexes Used in Tables
   6. Table 1 Cycloisomerizations of 1,5-Enynes
   7. Table 2 Cycloisomerizations of 1,6-Enynes
   8. Table 3 Cycloisomerizations of 1,7- and Higher Enynes
   9. Table 4 Formation of Cyclobutenes and Related Compounds From 1,n-Enynes
   10. Table 5 Intramolecular Additions of Enols and Enol Ethers to Alkynes
   11. Table 6 Intermolecular Additions of Enols and Enol Ethers to Enynes
   12. Table 7 Intramolecular Cyclopropanations of 1,6-Enynes
   13. Table 8 Intermolecular Cyclopropanations of 1,6-Enynes
   14. Table 9 Cycloisomerizations of 1,3-Enynes via Propargylic Acyloxy Migration
   15. Table 10 Cycloisomerizations of 1,4-Enynes via Propargylic Acyloxy Migration
   16. Table 11 Cycloisomerizations of 1,5-Enynes via Propargylic Acyloxy Migration
   17. Table 12 Cycloisomerizations of 1,6-Enynes via Propargylic Acyloxy Migration
   18. Table 13 Cycloisomerizations of 1,n-Enynes (n>6) via Propargylic Acyloxy Migration
   19. Table 14 Cycloisomerizations of Hydroxy- and Alkoxy-Substituted 1,n-Enynes
   20. Table 15 Hydroxy- and Alkoxycyclizations of 1,n-Enynes
   21. Table 16 Aminocyclizations of 1,n-Enynes
   22. Table 17 Intramolecular Additions of Aryl and Alkenyl Nucleophiles to Enynes
   23. Table 18 Intermolecular Additions of Aryl Nucleophiles to Enynes
   24. Table 19 Intramolecular Additions of Carbonyl Compounds to Enynes
   25. Table 20 Intermolecular Additions of Carbonyl Compounds to Enynes
   26. Table 21 Cyclizations of Arylalkynes by Friedel-Crafts Processes
   27. Table 22 Intramolecular Reactions of Furans and Oxazoles with Alkynes
   28. Table 23 Intermolecular Reactions of Furans with Alkynes
10. References

Acknowledgments

We thank our past and present coworkers who have contributed to the development of gold-catalyzed chemistry in our group at the Universidad Autónoma de Madrid and at the Institute of Chemical Research of Catalonia (ICIQ) in Tarragona. We also thank the MINECO, the AGAUR, the European Research Council (Advanced Grant No. 321066), and the ICIQ Foundation for support.

Introduction

Gold salts and complexes are the most reactive catalysts for the electrophilic activation of alkynes under homogeneous conditions. This property was first demonstrated in the efficient additions of alcohols and water to alkynes, which occur under very mild conditions.1, 2

Nucleophilic attack onto a [AuL]+-activated alkyne...