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. 2015 Aug 18;48(8):2354-65.
doi: 10.1021/acs.accounts.5b00054. Epub 2015 Jul 22.

Advances in nickel-catalyzed cycloaddition reactions to construct carbocycles and heterocycles

Ashish Thakur  1 , Janis Louie  1
Affiliations

Advances in nickel-catalyzed cycloaddition reactions to construct carbocycles and heterocycles

Ashish Thakur et al. Acc Chem Res. .

Abstract

Transition-metal catalysis has revolutionized the field of organic synthesis by facilitating the construction of complex organic molecules in a highly efficient manner. Although these catalysts are typically based on precious metals, researchers have made great strides in discovering new base metal catalysts over the past decade. This Account describes our efforts in this area and details the development of versatile Ni complexes that catalyze a variety of cycloaddition reactions to afford interesting carbocycles and heterocycles. First, we describe our early work in investigating the efficacy of N-heterocyclic carbene (NHC) ligands in Ni-catalyzed cycloaddition reactions with carbon dioxide and isocyanate. The use of sterically hindered, electron donating NHC ligands in these reactions significantly improved the substrate scope as well as reaction conditions in the syntheses of a variety of pyrones and pyridones. The high reactivity and versatility of these unique Ni(NHC) catalytic systems allowed us to develop unprecedented Ni-catalyzed cycloadditions that were unexplored due to the inefficacy of early Ni catalysts to promote hetero-oxidative coupling steps. We describe the development and mechanistic analysis of Ni/NHC catalysts that couple diynes and nitriles to form pyridines. Kinetic studies and stoichiometric reactions confirmed a hetero-oxidative coupling pathway associated with this Ni-catalyzed cycloaddition. We then describe a series of new substrates for Ni-catalyzed cycloaddition reactions such as vinylcyclopropanes, aldehydes, ketones, tropones, 3-azetidinones, and 3-oxetanones. In reactions with vinycyclopropanes and tropones, DFT calculations reveal noteworthy mechanistic steps such as a C-C σ-bond activation and an 8π-insertion of vinylcyclopropane and tropone, respectively. Similarly, the cycloaddition of 3-azetidinones and 3-oxetanones also requires Ni-catalyzed C-C σ-bond activation to form N- and O-containing heterocycles.

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Conflict of interest statement

Notes

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1
Mechanism of Ni-Catalyzed Cycloaddition of Diyne and Heterocumulene
Scheme 2
Scheme 2
Ni/IPr-Catalyzed Cycloaddition of Symmetrical Diynes with CO2
Scheme 3
Scheme 3
Ni/IPr-Catalyzed Cycloaddition of Unsymmetrical Diynes and CO2
Scheme 4
Scheme 4
Mechanism of Ni/IPr-Catalyzed Cycloaddition of Diynes and CO2
Scheme 5
Scheme 5
Ni/SIPr-Catalyzed Catalyzed Cycloaddition of Diynes and Isocyanates
Scheme 6
Scheme 6
Ni/SIPr-Catalyzed Cycloaddition of 3-Hexyne and Phenyl Isocyanate
Scheme 7
Scheme 7
Ni/PEt3-Catalyzed Cycloaddition of Alkynes and Isocyanates
Scheme 8
Scheme 8
Ni/IPr-Catalyzed Synthesis of Pyrimidine-Diones via Cycloaddition of Alkynes and Isocyanates
Scheme 9
Scheme 9
Proposed Mechanism for the Intermolecular Cycloaddition of Alkynes and Isocyanates To Form Pyridones
Scheme 10
Scheme 10
Proposed Mechanism for the Synthesis of Pyrimidine-Diones
Scheme 11
Scheme 11
Ni/IPr-Catalyzed Cycloaddition of Enynes and Isocyanates
Scheme 12
Scheme 12
Ni/SIPr-Catalyzed Cycloaddition of Diynes and Nitriles
Scheme 13
Scheme 13
Ni/SIPr-Catalyzed Cycloaddition of Unsymmetrical Diyne with Acetonitrile and 3-Hexyne with Benzonitrile
Scheme 14
Scheme 14
Ni/IMes- and Ni/SIPr-Catalyzed Cycloaddition of Diynes and Cyanamides
Scheme 15
Scheme 15
Ni/Xantphos-Catalyzed Cycloaddition of Diyne 39 and Ketenimine 40
Scheme 16
Scheme 16
Ni/Xantphos-Catalyzed Cycloaddition of Diynes with Nitriles and Cyanamides
Scheme 17
Scheme 17
Synthesis of [Ni(IPr)RCN]2 and Their Catalytic Activity for the Cycloaddition of Diynes and Nitriles
Scheme 18
Scheme 18
Proposed Mechanism for the [Ni(IPr)RCN]2-Catalyzed Cycloaddition of Diynes and Nitriles
Scheme 19
Scheme 19
Proposed Mechanism for the Ni(IPr)2-Catalyzed Cycloaddition of Diynes and Nitriles
Scheme 20
Scheme 20
Ni/SIPr-Catalyzed Cycloaddition of Terminal Alkynes and Cycnamides
Scheme 21
Scheme 21
Proposed Mechanism for the Ni/SIPr-Catalyzed Cycloaddition of Terminal Alkynes and Cycnamides
Scheme 22
Scheme 22. Ni/SIPr-Catalyzed Cycloaddition of Diynes and Aldehydes
aProduct was obtained as an equilibrium mixture of dienone (major) and pyran (minor).
Scheme 23
Scheme 23
Ni/SIPr-Catalyzed Cycloaddition of Internal 2,7-Diyne and Terminal 1,6-Diyne with Benzaldehyde
Scheme 24
Scheme 24
Proposed Mechanism for the Formation of Diverse Dienones
Scheme 25
Scheme 25
Ni/SIPr-Catalyzed Cycloaddition of Enynes and Aldehydes
Scheme 26
Scheme 26
Proposed Mechanism for the Ni/SIPr-Catalyzed Cycloaddition of Enynes and Aldehydes
Scheme 27
Scheme 27
Ni/SIPr-Catalyzed Cycloaddition of Enynes and Ketones
Scheme 28
Scheme 28
Proposed Mechanism for the Ni/SIPr-Catalyzed Cycloaddition of Enynes and Ketones
Scheme 29
Scheme 29
Ni/DPPB-Catalyzed Cycloaddition of Diynes and Ketenes
Scheme 30
Scheme 30
Enantioselective Ni/BINAP-Catalyzed Cycloaddition of Diyne and Ketene
Scheme 31
Scheme 31
Ni/SIPr-Catalyzed Cycloaddition of Diynes and Tropone
Scheme 32
Scheme 32
Proposed Mechanism for Ni-Catalyzed Cycloaddition of Diynes and Tropone
Scheme 33
Scheme 33
Ni/PPh3-Catalyzed Cycloaddition of Alkynes and 3-Azetidinones
Scheme 34
Scheme 34
Ni/PPh3-Catalyzed Cycloaddition of 4-Octyne and Chiral 2-Substituted Azetidinone
Scheme 35
Scheme 35
Proposed Mechanism for the Ni/PPh3-Catalyzed Cycloaddition of Sterically Biased Alkynes with 3-Azetidinones
Scheme 36
Scheme 36
Proposed Mechanism for the Ni/PPh3-Catalyzed Cycloaddition of Electronically Biased Alkynes with 3-Azetidinones
Scheme 37
Scheme 37
Ni/IPr-Catalyzed Cycloaddition of Diynes with 3-Azetdidinones and 3-Oxetanones
Scheme 38
Scheme 38
Ni/P(p-tol)3-Catalyzed Cycloaddition of 1,3-Dienes with 3-Azetidinones and 3-Oxetanones
Scheme 39
Scheme 39
Ni/P(p-tol)3-Catalyzed Cycloaddition of Diene with Chiral 2-Substituted Azetidinone and Loss of Enantioselectivity of Chiral Azetidinone
Scheme 40
Scheme 40
Proposed Mechanism of Ni/P(p-tol)3-Catalyzed Cycloaddition of 1,3-Dienes with 3-Azetidinones and 3-Oxetanones
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