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. 2024 Mar 1;89(5):3123-3132.
doi: 10.1021/acs.joc.3c02572. Epub 2024 Feb 20.

Comprehensive Mechanistic Analysis of Palladium- and Nickel-Catalyzed α,β-Dehydrogenation of Carbonyls via Organozinc Intermediates

Alexandra K Bodnar  1 , Suzanne M Szewczyk  1 , Yang Sun  1 , Yifeng Chen  1 , Anson X Huang  1 , Timothy R Newhouse  1
Affiliations

Comprehensive Mechanistic Analysis of Palladium- and Nickel-Catalyzed α,β-Dehydrogenation of Carbonyls via Organozinc Intermediates

Alexandra K Bodnar et al. J Org Chem. .

Abstract

Introducing degrees of unsaturation into small molecules is a central transformation in organic synthesis. A strategically useful category of this reaction type is the conversion of alkanes into alkenes for substrates with an adjacent electron-withdrawing group. An efficient strategy for this conversion has been deprotonation to form a stabilized organozinc intermediate that can be subjected to α,β-dehydrogenation through palladium or nickel catalysis. This general reactivity blueprint presents a window to uncover and understand the reactivity of Pd- and Ni-enolates. Within this context, it was determined that β-hydride elimination is slow and proceeds via concerted syn-elimination. One interesting finding is that β-hydride elimination can be preferred to a greater extent than C-C bond formation for Ni, more so than with Pd, which defies the generally assumed trends that β-hydride elimination is more facile with Pd than Ni. The discussion of these findings is informed by KIE experiments, DFT calculations, stoichiometric reactions, and rate studies. Additionally, this report details an in-depth analysis of a methodological manifold for practical dehydrogenation and should enable its application to challenges in organic synthesis.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Previous dehydrogenation methodologies.
Figure 2.
Figure 2.
Proposed catalytic cycle.
Figure 3.
Figure 3.
Examination of CyanH and its derivatives as ligands.
Figure 4.
Figure 4.
Allylation is suppressed by ZnCl2.
Figure 5.
Figure 5.
From KIE and competition experiments, β-hydride elimination or reductive elimination is turnover limiting.
Figure 6.
Figure 6.
Lack of facial selectivity results in an intramolecular KIE of 1.0.
Figure 7.
Figure 7.
β-Hydride elimination is a turnover-limiting step and proceeds through concerted syn-elimination. Calculations were performed at the ωb97X-D/6–311+G(d,p)-LANL2DZ(Ni,Pd)//ωb97X-D/def2TZVP-LANL2DZ(Pd,Ni)-SMD-THF level of theory.
See this image and copyright information in PMC

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