Cobalt bromide is an inorganic compound with the chemical formula CoBr2. Its anhydrous substance is a green solid, soluble in water. Alkenyl is an important class of organic molecular skeleton, which widely exists in drug molecules, natural products and synthetic intermediates. The Wittig reaction, olefin metathesis reaction, Heck reaction, and alkyne reduction are classic alkenes synthesis methods; in recent years, alkyne hydrogen functionalization has gradually become a new strategy for alkenes synthesis. For example, copper-hydrogen and nickel-hydrogen species can undergo regio- and stereoselective hydrometalation and alkylation of alkynes to give 1,1-disubstituted alkenes, 1,2-disubstituted alkenes, and trisubstituted alkenes. However, starting from the same alkyne raw material, it is both an opportunity and a challenge to achieve regiodivergent hydroalkylation to synthesize various olefin isomers by adjusting the electrical and steric properties of the ligand.
Cobalt-catalyzed ligand-mediated regiodivergent hydroalkylation of alkynes has been reported. Reaction In order to realize the hydroalkylation reaction of olefins, cobalt compounds are used as catalysts, and the ligands are reasonably selected, and finally (E)-1,2-disubstituted and 1,1-disubstituted alkenes are efficiently produced, which reflects the reactivity of the cobalt-hydrogen catalytic system and the feasibility of precise regulation of the ligand's regioselectivity.
Using alkyne and bromamide as model substrates, the researchers obtained alkene products through ligand-regulated regioselectivity. The reaction substrate has a wide range of applications, suitable for a variety of alkyne substrates such as alkyl alkynes, aryl alkynes, terminal alkynes, and internal alkynes; it is also suitable for halogenated hydrocarbon substrates such as primary or secondary non-activated alkyl halides and benzyl halides, etc. Regioselective divergent synthesis can be achieved by changing the ligand.
Mechanism experiments mainly include deuteration experiments, catalyst characterization, etc. Deuterium experiments showed that the regioselectivity and stereoselectivity of the reaction may originate from the cis-migration insertion of the Co-H intermediate to the alkyne, the process is irreversible, and the hydrogen is derived from DEMS. The researchers prepared cobalt complex catalyst 143 from CoBr2 and characterized its structure by X-ray diffraction. The ultraviolet-visible absorption spectrum results of complex 143 and the reaction solution show that: Co(II)Ln (L = L1, solvent, Br, etc.) maintains a high concentration before the end of the reaction.
The researchers proposed two possible reaction mechanisms, the main difference being the migratory insertion of Co(II)H species or Co(I)H species into alkynes. The researchers conducted a DFT computational study of the above two migration-insertion processes on a simplified reaction model. DFT calculations show that the migration insertion of Co(I)H species has a higher transition state energy barrier and is less likely. The regioselectivity of Co(II)H species migration and insertion is consistent with the experimental results: for bisoxazoline ligands, TS1D-L1M is more favorable than TS1'D-L1M (ΔΔG≠= -2.3 kcal/mol); For pyridine-oxazoline ligands, TS1D-L8M is more dominant (ΔΔG≠= -2.6 kcal/mol). The cobalt-catalyzed spin-crossover process lowers the overall activation barrier for the migratory insertion step. Energy decomposition analysis revealed that steric hindrance dominates the regioselectivity of L1M, and dispersion affects the regioselectivity of L8M.
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Reference
- Ligand-Controlled Cobalt-Catalyzed Regiodivergent Alkyne Hydroalkylation
J. Am. Chem. Soc., 2022
