Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jun 26;119(12):7478-7528.
doi: 10.1021/acs.chemrev.9b00079. Epub 2019 Apr 25.

Palladium/Norbornene Cooperative Catalysis

Jianchun Wang  1 , Guangbin Dong  1
Affiliations
Review

Palladium/Norbornene Cooperative Catalysis

Jianchun Wang et al. Chem Rev. .

Abstract

Palladium/norbornene cooperative catalysis has emerged as a distinct approach to construct polyfunctionalized arenes from readily available starting materials. This Review provides a comprehensive overview of this field, including the early stoichiometric investigations, catalytic reaction developments, as well as the applications in the syntheses of bioactive compounds and polymers. The section of catalytic reactions is divided into two parts according to the reaction initiation mode: Pd(0)-initiated reactions and Pd(II)-initiated reactions.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Out-of-Plane Bending Angles for NBE and norbornadiene.
Scheme 1.
Scheme 1.
Pd/NBE Catalysis: Merge of Ipso and Ortho Functionalizations
Scheme 2.
Scheme 2.
Migratory Insertion of NBE into the Pd–Ph Bond
Scheme 3.
Scheme 3.
Pd-Catalyzed Interrupted Heck Reaction of Phenyl Bromide with NBE
Scheme 4.
Scheme 4.
Stoichiometric Studies on the Cyclopalladation Step
Scheme 5.
Scheme 5.
Kinetic Isotopic Effect on the Cyclopalladation Step in Stoichiometric Studies
Scheme 6.
Scheme 6.
Formation of Intramolecular η2-Arene Palladium Species
Scheme 7.
Scheme 7.
Stoichiometric Reaction between ANP and Methyl Iodide
Scheme 8.
Scheme 8.
Stoichiometric Reaction between ANP and Allyl/Benzyl Bromides
Scheme 9.
Scheme 9.
Unselective Reaction between Para-Substituted Aryl Bromides with NBE
Scheme 10.
Scheme 10.
Reaction between Iodobenzene with NBE under Jeffery’s Conditions
Scheme 11.
Scheme 11.
Discovery of the “Ortho Effect”
Scheme 12.
Scheme 12.
Reversible Insertion of Nickel–Allyl Bond into NBE
Scheme 13.
Scheme 13.
NBE Extrusion after Double Ortho Functionalizations
Scheme 14.
Scheme 14.
General Catalytic Cycle for Pd/NBE Catalysis
Scheme 15.
Scheme 15.
Selectivity Issue for Oxidative Addition of Pd(0) versus ANP
Scheme 16.
Scheme 16.
Measurement of the Migratory Insertion Barriers into NBE
Scheme 17.
Scheme 17.
Activation Barrier of NBE or Acrylate Directed C–H Metalation
Scheme 18.
Scheme 18.
Equilibrium of NBE Insertion/Extrusion
Scheme 19.
Scheme 19.
Absence of Norbornadiene Extrusion in Stoichiometric Reactions
Scheme 20.
Scheme 20.
Acyclic Olefin Mediated Ortho Arylation
Scheme 21.
Scheme 21.
Structures of Alternative Substituted NBEs
Scheme 22.
Scheme 22.
First Catalytic Example in the Pd/NBE Catalysis
Scheme 23.
Scheme 23.
Ortho Alkylation/Ipso Heck Reaction of Aryl Iodides
Scheme 24.
Scheme 24.
Expansion of the Ortho Alkylation/Ipso Heck Reaction of Heteroaryl Iodides
Scheme 25.
Scheme 25.
Ortho Alkylation/Ipso Heck/Aza-Michael Cascade of Aryl Iodides
Scheme 26.
Scheme 26.
Ortho Trifluoroethylation/Ipso Heck Reaction of Aryl Iodides
Scheme 27.
Scheme 27.
Employing Secondary Alkyl Halides in the Pd/NBE catalysis
Scheme 28.
Scheme 28.
Ortho Silylmethylation/Ipso Heck Reaction of Aryl Iodides
Scheme 29.
Scheme 29.
Ortho Methylation/Ipso Heck Reaction of Aryl Iodides
Scheme 30.
Scheme 30.
Ortho Alkylation/Ipso Suzuki–Miyaura Reaction of Aryl Iodides
Scheme 31.
Scheme 31.
Asymmetric Ortho Alkylation/Ipso Suzuki–Miyaura Reaction of Aryl Iodides
Scheme 32.
Scheme 32.
Ortho Alkylation/Ipso Sonogashira Reaction of Aryl Iodides
Scheme 33.
Scheme 33.
Ortho Alkylation/Ipso Sonogashira Reaction of Aryl Iodides Using Masked Alkynes
Scheme 34.
Scheme 34.
Ortho Alkylation/Ipso Sonogashira Reaction of Aryl Iodides Using Unprotected Alkynes
Scheme 35.
Scheme 35.
Ortho Alkylation/Ipso Hydrogenation Reaction of Aryl Iodides
Scheme 36.
Scheme 36.
Ortho Benzylation/Ipso Hydrogenation Reaction of Aryl Iodides
Scheme 37.
Scheme 37.
Ortho Alkylation/Ipso Cyanation Reaction of Aryl Iodides
Scheme 38.
Scheme 38.
Ortho Alkylation/Ipso Carbene Insertion Reaction of Aryl Iodides
Scheme 39.
Scheme 39.
Ortho Alkylation/Ipso Direct Arylation Reaction of Aryl Iodides
Scheme 40.
Scheme 40.
Ortho Alkylation/Ipso Enolate Coupling Reaction of Aryl Iodides
Scheme 41.
Scheme 41.
Four Types of Intramolecular Couplings
Scheme 42.
Scheme 42.
Ortho Alkylation/Ipso Intramolecular Heck Coupling Reaction of Aryl Iodides
Scheme 43.
Scheme 43.
Synthesis of Tetrahydronapthalenes or Indanes via Ortho Alkylation/Ipso Redox-Relay Heck Coupling Reaction of Aryl Iodides
Scheme 44.
Scheme 44.
Representative Examples of Ortho Alkylation/Ipso Intramolecular Direct Arylation Reaction of Aryl Iodides
Scheme 45.
Scheme 45.
Ortho Alkylation/Ipso Intramolecular C–N Coupling Reaction of Aryl Iodides
Scheme 46.
Scheme 46.
Ortho Alkylation/Ipso Intramolecular Enolate Coupling Reaction of Aryl Iodides
Scheme 47.
Scheme 47.
Ortho Alkylation of Aryl Iodides Followed by Alkyne Insertion
Scheme 48.
Scheme 48.
Synthesis of Bicyclic Structures by Type B Intermolecular Couplings
Scheme 49.
Scheme 49.
Synthesis of Bicyclic Structures by Type C Intermolecular Couplings
Scheme 50.
Scheme 50.
Synthesis of Tricyclic Structures by Type D Intermolecular Coupling
Scheme 51.
Scheme 51.
Synthesis of Indoles by Ortho Alkylation of Aryl Iodides Using 2H-Azirines
Scheme 52.
Scheme 52.
Synthesis of 2,3-Dihydrobenzofurans by Ortho Alkylation of Aryl Iodides Using Epoxides
Scheme 53.
Scheme 53.
Synthesis of Isochromans by Ortho Alkylation of Aryl Iodides Using Epoxides
Scheme 54.
Scheme 54.
Synthesis of Indolines by Ortho Alkylation of Aryl Iodides Using Aziridines
Scheme 55.
Scheme 55.
Synthesis of Tetrahydroisoquinolines by Ortho Alkylation of Aryl Iodides Using Aziridines
Scheme 56.
Scheme 56.
Synthesis of Phenanthrenes from Ortho-Substituted Aryl Iodides and Internal Alkynes
Scheme 57.
Scheme 57.
Homo Ortho Arylation/Ipso Heck reaction of Aryl Iodides
Scheme 58.
Scheme 58.
Homo Ortho Arylation/Ipso Functionalizations of Aryl Iodides
Scheme 59.
Scheme 59.
Selectivity Problems in Cross Ortho Arylation
Scheme 60.
Scheme 60.
Tentative Explanations on the Observed Selectivity
Scheme 61.
Scheme 61.
Cross Ortho Arylation/Ipso Heck of Aryl Iodides
Scheme 62.
Scheme 62.
Cross Ortho Arylation/Ipso Heck Followed by Michael Reaction
Scheme 63.
Scheme 63.
Cross Ortho Arylation/Ipso Functionalizations of Aryl Iodides
Scheme 64.
Scheme 64.
π-Extension Reaction Using 2-Halobenzoic Acids
Scheme 65.
Scheme 65.
DFT Calculations on the Origin of the “Ortho Effect”
Scheme 66.
Scheme 66.
Overcoming Ortho Effect with Substituted NBEs
Scheme 67.
Scheme 67.
Synthesis of Fused Rings via Ortho-Arylation Ipso-C–N or C–O Coupling
Scheme 68.
Scheme 68.
Dearomatizing [2+2+1] Annulation of Bromonaphthols with Aryl Iodides and Alkynes
Scheme 69.
Scheme 69.
Ortho Arylation/Ipso C–O Coupling of 4-Iodo-2-Quinolones
Scheme 70.
Scheme 70.
Switching Regioselectivity for Reductive Elimination by Chelation
Scheme 71.
Scheme 71.
Formation of Dibenzoazepine Derivatives by Ortho Arylation of Aryl Iodides with o-Bromoanilines
Scheme 72.
Scheme 72.
Divergent Preparation of Heterocyclic Sulfoximines
Scheme 73.
Scheme 73.
Ortho Arylation/Intramolecular Ipso 1,2-Addition of Aryl Iodides
Scheme 74.
Scheme 74.
Type B Intramolecular Coupling in Ortho Arylation of Aryl Iodides
Scheme 75.
Scheme 75.
Ortho Amination/Ipso Hydrogenation of Aryl Iodides
Scheme 76.
Scheme 76.
Ortho Amination/Ipso Functionalizations of Aryl Iodides
Scheme 77.
Scheme 77.
Ortho Amination/Ipso Borylation and Derivatization of Aryl Iodides
Scheme 78.
Scheme 78.
Type B Intramolecular Couplings in Ortho Amination
Scheme 79.
Scheme 79.
Initial Reports of Ortho Acylation Reaction
Scheme 80.
Scheme 80.
DFT Calculations on the Reaction of ANP with Anhydrides
Scheme 81.
Scheme 81.
Expanding Scope of Ortho Acylation of Aryl Iodides Using Mixed Anhydride
Scheme 82.
Scheme 82.
Different ipso Functionalizations in ortho Acylation Reaction
Scheme 83.
Scheme 83.
Ortho Acylation/Ipso Thiolation and Selenation Reaction of Aryl Iodides
Scheme 84.
Scheme 84.
Ipso Intermolecular Couplings in Ortho Acylation Reaction
Scheme 85.
Scheme 85.
Ortho Alkoxylcarbonylation Reaction of Aryl Iodides and Its Extension
Scheme 86.
Scheme 86.
Ortho Aminocarbonylation/Ipso Intramolecular Coupling Reactions
Scheme 87.
Scheme 87.
Ortho Alkylation/Type C Intramolecular Couplings of Aryl Bromides
Scheme 88.
Scheme 88.
Ortho Arylation of Aryl Triflates
Scheme 89.
Scheme 89.
Ortho Amination of Aryl Bromides
Scheme 90.
Scheme 90.
Other Ortho Functionalizations of Aryl Bromides
Scheme 91.
Scheme 91.
Halide Effect in the Pd/NBE Catalysis
Scheme 92.
Scheme 92.
Synthesis of Benzo[1,6]naphthyridinones from 4-Bromoquinolines
Scheme 93.
Scheme 93.
“Ortho Constraint” in the Pd/NBE Catalysis
Scheme 94.
Scheme 94.
Violation of the “Ortho Constraint” in Special Cases
Scheme 95.
Scheme 95.
Controlling Relative Rates for C–H Metalation versus β-Carbon Elimination Using Modified NBEs
Scheme 96.
Scheme 96.
Mono Ortho Functionalization of Aryl Iodides without Ortho Substituents
Scheme 97.
Scheme 97.
Mono Ortho Functionalization of Iodobenzene
Scheme 98.
Scheme 98.
Complementary Functionalization of Strychnine
Scheme 99.
Scheme 99.
Other Types of Ortho Functionalizations of Aryl Iodides
Scheme 100.
Scheme 100.
2-Alkylation of Indoles via Pd/NBE Catalysis
Scheme 101.
Scheme 101.
Catalytic Cycle for 2-Alkylation of Indoles
Scheme 102.
Scheme 102.
Evidence for the Formation of the N-NBE Type Palladacycle
Scheme 103.
Scheme 103.
Reaction Extension to 2-Alkylation of Pyrroles and Indoles
Scheme 104.
Scheme 104.
2-Arylation of Indoles via the Pd/NBE Catalysis
Scheme 105.
Scheme 105.
2-Trifluoroethylation of Indoles via Pd/NBE Catalysis
Scheme 106.
Scheme 106.
General Reaction Pathway for the Meta-Functionalization of Arenes Using Ortho-DGs
Scheme 107.
Scheme 107.
Meta-Alkylation/Arylation of Phenylacetic-Acid-Derived Amides
Scheme 108.
Scheme 108.
Meta-Arylation of Simple Tertiary Benzyl Amines
Scheme 109.
Scheme 109.
Expanding Scope of Meta-Alkylation/Arylation with a Modified NBE
Scheme 110.
Scheme 110.
Meta-Arylation of Oxalyl Amide-Protected β-Arylethylamines
Scheme 111.
Scheme 111.
Meta-Arylation of Anilines, Phenols, and Heterocycles with Pyridine-Type DGs
Scheme 112.
Scheme 112.
Meta-Arylation of Benzylamines and Protected Aldehydes with Pyridine-Type DGs
Scheme 113.
Scheme 113.
Meta-Arylation of Benzyl Alcohol with Quinoline-Type DG
Scheme 114.
Scheme 114.
Meta-Arylations with the Amide-Type DG
Scheme 115.
Scheme 115.
Meta-Arylations of Phenylacetic Acids
Scheme 116.
Scheme 116.
Enantioselective Remote Meta C–H Arylation and Alkylation of (Homo)Benzylamines with Pyridine-Type DGs
Scheme 117.
Scheme 117.
Meta-Amination of Anilines and Phenols with Pyridine-Type DGs
Scheme 118.
Scheme 118.
Meta-Alkynylation and Chlorination with Pyridine-Type DGs
Scheme 119.
Scheme 119.
Transmetalation-Initiated Pd/NBE Catalysis
Scheme 120.
Scheme 120.
Oxidative Ortho Alkylation/Ipso Heck Reaction of Arylboronic Acids
Scheme 121.
Scheme 121.
Redox-Neutral Ortho Functionalizations of Aryl Nucleophiles
Scheme 122.
Scheme 122.
Redox-Neutral Ortho Functionalizations of Aryl Boroxines
Scheme 123.
Scheme 123.
Total Synthesis of (+)-Linoxepin
Scheme 124.
Scheme 124.
Synthesis of (±)-Fufenozide and (±)-Eptazocine
Scheme 125.
Scheme 125.
Synthesis of Carbazomycin A, Nitidine, Assoanine, and Pratosine
Scheme 126.
Scheme 126.
Total Synthesis of (+)-Rhazinal
Scheme 127.
Scheme 127.
Syntheses of Abilify and Flunixin
Scheme 128.
Scheme 128.
Formal Synthesis of Ketoprofen
Scheme 129.
Scheme 129.
Syntheses of Pauciflorol F and Acredinone A
Scheme 130.
Scheme 130.
Total Syntheses of (±)-Aspidospermidine and (±)-Goniomitine
Scheme 131.
Scheme 131.
Total Syntheses of (+)-Kopsihainanine A, (−)-Aspidophylline A, and (+)-Strictamine
Scheme 132.
Scheme 132.
Synthesis of Ladder Polymers Using Catalytic Arene-NBE Annulation
Scheme 133.
Scheme 133.
Multicomponent “In Situ Functionalization” Polymerization by Palladium/NBE Catalysis
Scheme 134.
Scheme 134.
Synthesis of the Water-Soluble PPE with Meta Side Chains
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Taylor RD; MacCoss M; Lawson ADG ″Rings in Drugs″. J. Med. Chem 2014, 57, 5845–5859. - PubMed
    1. Tsuji J Palladium Reagents and Catalysts: New Perspectives for the 21st Century; John Wiley & Sons, Ltd, 2005.
    1. Terrier F Modern Nucleophilic Aromatic Substitution; Wiley-VCH Verlag GmbH & Co. KGaA, 2013.
    1. Negishi E.-i.; De Meijere A Handbook of Organopalladium Chemistry for Organic Synthesis; John Wiley & Sons, Inc., 2003.
    1. Buncel E; Dust JM; Terrier F ″Rationalizing the Regioselectivity in Polynitroarene Anionic σ-Adduct Formation. Relevance to Nucleophilic Aromatic Substitution″. Chem. Rev 1995, 95, 2261–2280.

Publication types

MeSH terms