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. 2013 Sep 9;32(17):4952-4960.
doi: 10.1021/om400666k.

Mechanistic Evaluation of the Ni(IPr)2-Catalyzed Cycloaddition of Alkynes and Nitriles to Afford Pyridines: Evidence for the Formation of a Key η1-Ni(IPr)2(RCN) Intermediate

Ryan M Stolley  1 , Hung A Duong  1 , Janis Louie  1
Affiliations

Mechanistic Evaluation of the Ni(IPr)2-Catalyzed Cycloaddition of Alkynes and Nitriles to Afford Pyridines: Evidence for the Formation of a Key η1-Ni(IPr)2(RCN) Intermediate

Ryan M Stolley et al. Organometallics. .

Abstract

A detailed mechanistic evaluation of the Ni(IPr)2-catalyzed [2+2+2]-cycloaddition of diynes and nitriles was 2 conducted. Through kinetic analysis of these reactions, observed regioselectivities of the products, and stoichiometric reactions, Ni(IPr)2-catalyzed cycloadditions of diynes and nitriles appear to proceed by a heterooxidative coupling mechanism, contrary to other common cycloaddition catalysts. Reaction profiles demonstrated strong dependence in nitrile, resulting in variable nitrile-dependent resting states. Strong coordination and considerable steric bulk of the carbene ligands facilitate selective initial binding of nitrile thereby forcing a heterocoupling pathway. In situ IR data suggests the initial binding of the nitrile resides in a rare, η1-bound conformation. Following nitrile coordination are a rate-determining hapticity shift of the nitrile and subsequent loss of carbene. Alkyne coordination then leads to heterooxidative coupling, insertion of the pendant alkyne, and reductive elimination to afford pyridine products.

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Figures

Figure 1
Figure 1. Plots of [2] vs time, kobs vs [IPr], kobs vs [10], and kobs vs [MeCN] for the Ni(IPr)2 -catalyzed cycloaddition of 1 and MeCN at -20 °C in C7D8
Figure 2
Figure 2
Plots of [15] vs time, kobs vs [IPr], kobs vs [10], and kobs vs [14] for the Ni(IPr)2-catalyzed cycloaddition of 1 and 14 at 26 °C in C7D8.
Figure 3
Figure 3
Absorption intensity at 2188 cm-1 vs. reaction time for the cycloaddition of 1 (1 equiv) and MeCN (5 equiv) mediated by Ni(IPr)2 (50 mol%).
Scheme 1
Scheme 1
Commonly Proposed Homocoupling mechanism for the [2+2+2]-cycloaddition of Nitrile and Alkynes.
Scheme 2
Scheme 2. Proposed Catalytic Cycle for the [Ni(IPr)RCN]2-Catalyzed Cycloaddition of Diyne and Nitriles
Scheme 3
Scheme 3. Possible Catalytic Pathways for the Ni-Catalyzed [2+2+2]-Cycloaddition of Diynes and Nitriles
Scheme 4
Scheme 4. Homocoupling Catalytic Pathway
Scheme 5
Scheme 5
Proposed Intermediates for the Observed Regiochemistry.
Scheme 6
Scheme 6. Nickel-Mediated Transmetallative Routes to Pyridine Formation
Scheme 7
Scheme 7
Proposed Catalytic Cycle with Initial Nitrile Coordination.
Scheme 8
Scheme 8
Proposed Catalytic Cycle with Initial Nitrile Coordination.
Scheme 9
Scheme 9. Proposed Catalytic Cycle of the Ni(IPr)2-Catalyzed [2+2+2]-Cycloaddition of Diynes and Nitriles
Scheme 10
Scheme 10. Product distribution as a function of competitive binding of nitriles and terminal alkynes
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References

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