| Autor: |
Mendelsohn LN; Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States., Pavlovic L; Department of Chemistry, UiT - The Arctic University of Norway, Tromsø N-9037, Norway., Zhong H; Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States., Friedfeld MR; Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States., Shevlin M; Department of Process Research & Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States., Hopmann KH; Department of Chemistry, UiT - The Arctic University of Norway, Tromsø N-9037, Norway., Chirik PJ; Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Chemical Society [J Am Chem Soc] 2022 Aug 31; Vol. 144 (34), pp. 15764-15778. Date of Electronic Publication: 2022 Aug 11. |
| DOI: |
10.1021/jacs.2c06454 |
| Abstrakt: |
The mechanism of the asymmetric hydrogenation of prochiral enamides by well-defined, neutral bis(phosphine) cobalt(0) and cobalt(II) precatalysts has been explored using( R , R )- iPr DuPhos (( R , R )- iPr DuPhos = (+)-1,2-bis[(2 R ,5 R )-2,5-diisopropylphospholano]benzene) as a representative chiral bis(phosphine) ligand. A series of ( R , R )-( iPr DuPhos)Co(enamide) (enamide = methyl-2-acetamidoacrylate (MAA), methyl( Z )-α-acetamidocinnamate (MAC), and methyl( Z )-acetamido(4-fluorophenyl)acrylate ( 4F MAC)) complexes ( 1-MAA , 1-MAC , and 1- 4F MAC ), as well as a dinuclear cobalt tetrahydride, [( R , R )-( iPr DuPhos)Co] 2 (μ 2 -H) 3 (H) ( 2 ), were independently synthesized, characterized, and evaluated in both stoichiometric and catalytic hydrogenation reactions. Characterization of ( R , R )-( iPr DuPhos)Co(enamide) complexes by X-ray diffraction established the formation of the pro-( R ) diastereomers in contrast to the ( S )-alkane products obtained from the catalytic reaction. In situ monitoring of the cobalt-catalyzed hydrogenation reactions by UV-visible and freeze-quench electron paramagnetic resonance spectroscopies revealed ( R , R )-( iPr DuPhos)Co(enamide) complexes as the catalyst resting state for all the three enamides studied. Variable time normalization analysis kinetic studies of the cobalt-catalyzed hydrogenation reactions in methanol established a rate law that is first order in ( R , R )-( iPr DuPhos)Co(enamide) and H 2 but independent of the enamide concentration. Deuterium-labeling studies, including measurement of an H 2 /D 2 kinetic isotope effect and catalytic hydrogenations with HD, established an irreversible H 2 addition step to the bound enamide. Density functional theory calculations support that this step is both rate and selectivity determining. Calculations, as well as HD-labeling studies, provide evidence for two-electron redox cycling involving cobalt(0) and cobalt(II) intermediates during the catalytic cycle. Taken together, these experiments support an unsaturated pathway for the [( R , R )-( iPr DuPhos)Co]-catalyzed hydrogenation of prochiral enamides. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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