Back to Search
Start Over
Palladium-Catalyzed Enantioselective C(sp 3 )-H/C(sp 3 )-H Umpolung Coupling of N -Allylimine and α-Aryl Ketones.
- Source :
-
Journal of the American Chemical Society [J Am Chem Soc] 2021 Dec 08; Vol. 143 (48), pp. 20454-20461. Date of Electronic Publication: 2021 Nov 24. - Publication Year :
- 2021
-
Abstract
- Asymmetric functionalization of the C(sp <superscript>3</superscript> )-H bond is an attractive yet challenging strategy to achieve versatile bond-forming events, enabling the precise assembly of molecular complexity with minimal manipulation of functional groups. Here, we report an asymmetric C(sp <superscript>3</superscript> )-H/C(sp <superscript>3</superscript> )-H umpolung coupling of N -allylimine and coordinating α-aryl carbonyls by using chiral phosphoramidite-palladium catalysis. A wide variety of α-heteroaryl ketones and 2-acylimidazoles are nicely tolerated to open a convenient and tunable avenue for efficient synthesis of enantioenriched β-amino-γ,δ-unsaturated carbonyl derivatives with high levels of regio- and stereoselectivities, capable of providing a key intermediate for asymmetric synthesis of Focalin. This protocol showcases an umpolung reactivity of the N -allylimines through a concerted proton and two-electron transfer process to cleave the allylic C-H bond, effectively complementing established methodology for allylic C-H functionalization. An inner-sphere allylation pathway for both α-heteroaryl carbonyls and 2-acylimidazoles to attack the π-allylpalladium species is suggested by computational studies and experimental facts, wherein the nitrogen coordination to the palladium center enables the preference of branched regioselectivity.
Details
- Language :
- English
- ISSN :
- 1520-5126
- Volume :
- 143
- Issue :
- 48
- Database :
- MEDLINE
- Journal :
- Journal of the American Chemical Society
- Publication Type :
- Academic Journal
- Accession number :
- 34817997
- Full Text :
- https://doi.org/10.1021/jacs.1c10721