Chapter 1
Enantioselective, Rhodium-Catalyzed 1,4-Addition of Organoboron Reagents to Electron-Deficient Alkenes

Alan R. Burns and Hon Wai Lam

School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK

Iain D. Roy

School of Chemistry, University of Edinburgh, Joseph Black Building, The King's Buildings, David Brewster Road, Edinburgh, EH9 3FJ, UK

1. Acknowledgments
2. Introduction
3. Mechanism and Stereochemistry
   1. General Catalytic Cycle
   2. Stereochemical Model
4. Scope and Limitations
   1. Organoboron Reagents Employed
   2. Rhodium Precatalysts Employed
   3. Overview of Common Classes of Chiral Ligands Employed
      1. Chiral Bisphosphorus Ligands
      2. Chiral Monodentate Phosphorus Ligands
      3. Chiral Diene Ligands
      4. Chiral Bis-Sulfur Ligands
      5. Mixed Donor Ligands
         1. Chiral Phosphorus-Alkene Ligands
         2. Chiral Phosphorus-Sulfur Ligands
         3. Chiral Sulfur-Alkene Ligands
         4. Chiral Nitrogen-Alkene Ligands
         5. Chiral N-Heterocyclic Carbene Ligands
   4. Range of Electron-Deficient Alkenes Employed
      1. a,ß-Unsaturated Ketones
      2. a,ß-Unsaturated Aldehydes
      3. a,ß-Unsaturated Esters
      4. a,ß-Unsaturated Amides
      5. Alkenylphosphonyl Compounds
      6. Nitroalkenes
      7. Alkenylsulfonyl Compounds
      8. Alkenylazaarenes
      9. Electron-Deficient Alkenylarenes
      10. Borylalkenes
      11. Miscellaneous Acceptors
   5. Enantioselective, Domino Processes Involving a 1,4-Addition Step
5. Applications to Synthesis
   1. Baclofen and Rolipram
   2. Various Endothelin Receptor Antagonists
   3. Telcagepant (MK-0974)
   4. Isaindigotidione
   5. Hybridalactone and Ecklonialactones A, B, and C
   6. Pregabalin
   7. Kainic Acid
   8. Montanine-Type Amaryllidaceae Alkaloids
6. Comparison With Other Methods
   1. Enantioselective, Rhodium-Catalyzed 1,4-Additions of Organotitanium, Organozinc, Organoaluminum, Organosilicon, Organotin, Organoindium, and Organozirconium Reagents
      1. Organotitanium Reagents
      2. Organozinc Reagents
      3. Organoaluminum Reagents
      4. Organosilicon Reagents
      5. Organotin Reagents
      6. Organoindium Reagents
      7. Organozirconium Reagents
   2. Enantioselective Palladium-, Nickel-, or Copper-Catalyzed 1,4-Additions of Organoboron Reagents
      1. Palladium Catalysis
      2. Nickel Catalysis
      3. Copper Catalysis
   3. Copper-Catalyzed, Enantioselective 1,4-Additions of Non-Boron-Containing Organometallic Reagents
7. Experimental Conditions
8. Experimental Procedures
   1. 1. (R)-3-Phenylcyclohexanone [1,4-Arylation of a Cyclic Enone with an Arylboronic Acid Using a Chiral Bisphosphine Ligand].75
      2. Benzyl (5S)-N,N-bis(tert-Butoxycarbonyl)-5-(2,3-difluorophenyl)-6-nitro-d-norleucinate [Large-Scale 1,4-Arylation of a Nitroalkene with an Arylboronic Acid Using a Chiral Bisphosphine Ligand en route to Telcagepant].194
      3. 2,6-Dimethylphenyl (S)-3-Methyl-3,5-diphenylpentanoate [1,4-Arylation of a ß,ß-Disubstituted a,ß-Unsaturated Ester with a Sodium Tetraarylborate Using a Chiral Diene Ligand].69
      4. 2-[(R)-4-(tert-Butyldimethylsilyloxy)-2-(4-fluorophenylbutyl]pyrimidine [1,4-Arylation of an Alkenylazaarene with an Arylboronic Acid Using a Chiral Diene Ligand].55
      5. tert-Butyl (R)-4-(2-Methylprop-1-en-1-yl)-2-oxopyrrolidine-1-carboxylate [1,4-Alkenylation of a Cyclic a,ß-Unsaturated Amide with a Potassium Alkenyltrifluoroborate Using a Chiral Diene Ligand].198
      6. (1R,2S,3aR,7aR)-1-Acetyl-7a-hydroxy-3a-methyl-2-phenyloctahydro-4H-inden-4-one [Domino 1,4-Arylation of an Enone Followed by Aldol Cyclization onto a Ketone Using a Chiral Bisphosphine Ligand].182
      7. (R)-3-(Triethylsilyl)-3-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1H-inden-1-one [Synthesis of a 3,3-Disubstituted Indanone by a Domino Process Consisting of Alkyne Arylation with an Arylboronic Ester, 1,4-Rhodium Shift, and Cyclization onto an Enone Using a Chiral Bisphosphine Ligand].6
      8. (S)-tert-Butyl 3-(Benzo[d][1,3]dioxol-4-ylmethyl)-1-methyl-4-oxopyrrolidine-3-carboxylate [Domino 1,4-Arylation of an a,ß-Unsaturated Ester Followed by Dieckmann Cyclization onto an Ester Using a Chiral Bisphosphine Ligand].27
      9. Ethyl 2-Amino-5-(4-chlorophenyl)cyclopent-1-ene-1-carboxylate [Domino 1,4-Arylation of an a,ß-Unsaturated Ester Followed by Cyclization onto a Nitrile Using a Chiral Bisphosphine Ligand].183
      10. (R,E)-4´-Benzylidene-6´-methyl-3´,4´-dihydro-2´H-spiro[cyclopentane-1,1´-naphthalen]-3-one [Synthesis of a Spirocarbocycle by a Domino Process Consisting of Alkyne Arylation with a Sodium Tetraarylborate, 1,4-Rhodium Shift, and Cyclization onto a Tethered Trisubstituted Enone Using a Chiral Diene Ligand].189
9. Tabular Survey
   1. Chart 1. Chiral Bisphosphorus Ligands Used in Tables
   2. Chart 2. Chiral Monodentate Phosphorus Ligands Used in Tables
   3. Chart 3. Chiral Diene Ligands Used in Tables
   4. Chart 4. Chiral Phosphorus-Alkene Ligands Used in Tables
   5. Chart 5. Chiral Bis-Sulfur Ligands Used in Tables
   6. Chart 6. Chiral Phosphorus-Sulfur Ligands Used in Tables
   7. Chart 7. Chiral Sulfur-Alkene Ligands Used in Tables
   8. Chart 8. Chiral Nitrogen-Alkene Ligands Used in Tables
   9. Chart 9. Chiral N-Heterocyclic Carbene Ligands Used in Tables
   10. Chart 10. Miscellaneous Ligands Used in Tables
   11. Table 1A. Reactions of a, ß-Unsaturated Ketones with Arylboron Reagents
   12. Table 1B. Reactions of a, ß-Unsaturated Ketones with Heteroarylboron Reagents
   13. Table 1C. Reactions of a, ß-Unsaturated Ketones with Alkenylboron Reagents
   14. Table 2A. Reactions of a, ß-Unsaturated Aldehydes with Arylboron Reagents
   15. Table 2C. Reactions of a, ß-Unsaturated Aldehydes with Alkenylboron Reagents
   16. Table 3A. Reactions of a, ß-Unsaturated Esters with Arylboron Reagents
   17. Table 3B. Reactions of a, ß-Unsaturated Esters with Heteroarylboron Reagents
   18. Table 3C. Reactions of a, ß-Unsaturated Esters with Alkenylboron Reagents
   19. Table 4A. Reactions of a, ß-Unsaturated Amides with Arylboron Reagents
   20. Table 4B. Reactions of a, ß-Unsaturated Amides with Heteroarylboron Reagents
   21. Table 4C. Reactions of a, ß-Unsaturated Amides with Alkenylboron Reagents
   22. Table 5A. Reactions of Alkenylphosphoryl Compounds with Arylboron Reagents
   23. Table 6A. Reactions of Nitroalkenes with Arylboron Reagents
   24. Table 6C. Reactions of Nitroalkenes with Alkenylboron Reagents
   25. Table 7A. Reactions of Alkenylsulfonyl Compounds with Arylboron Reagents
   26. Table 7C. Reactions of Alkenylsulfonyl Compounds with Alkenylboron Reagents
   27. Table 8A. Reactions of Alkenylazaarenes with Arylboron Reagents
   28. Table 8C. Reactions of Alkenylazaarenes with Alkenylboron Reagents
   29. Table 9A. Reactions of Electron-Deficient Alkenylarenes with Arylboron Reagents
   30. Table 10A. Reactions of Borylalkenes with Arylboron Reagents
   31. Table 11A. Reactions of Miscellaneous Acceptors with Arylboron Reagents
   32. Table 12A. Domino Reactions with Arylboron Reagents
   33. Table 12B. Domino Reactions with Heteroarylboron Reagents
   34. Table 12D. Domino Reactions with Alkylboron Reagents
10. References

Acknowledgments

Prof. Gary Molander and Prof. Tomislav Rovis are gratefully acknowledged for their guidance and assistance in the writing of this chapter. We are extremely grateful to Dr. Linda S. Press for expert guidance in the preparation of the graphics and tables.

Introduction

The enantioselective 1,4-addition of organometallic reagents to electron-deficient alkenes is one of the most important methods for carbon-carbon bond formation.1-3 Within this field, the rhodium-catalyzed 1,4-addition of organoboron reagents to electron-deficient alkenes (Scheme 1) occupies a prominent position owing to (1) the availability, stability, and functional group tolerance of organoboron reagents, (2) the wide range of acceptors that may be employed, (3) the ability of a broad range of structurally distinct families of chiral ligands to induce high enantioselectivities in the reactions, and (4) the usually mild and experimentally convenient conditions, which generally do not require any special precautions to...