Photoinduced copper-catalysed asymmetric amidation via ligand cooperativity.
Nature
; 596(7871): 250-256, 2021 08.
Article
en En
| MEDLINE
| ID: mdl-34182570
ABSTRACT
The substitution of an alkyl electrophile by a nucleophile is a foundational reaction in organic chemistry that enables the efficient and convergent synthesis of organic molecules. Although there has been substantial recent progress in exploiting transition-metal catalysis to expand the scope of nucleophilic substitution reactions to include carbon nucleophiles1-4, there has been limited progress in corresponding reactions with nitrogen nucleophiles5-8. For many substitution reactions, the bond construction itself is not the only challenge, as there is a need to control stereochemistry at the same time. Here we describe a method for the enantioconvergent substitution of unactivated racemic alkyl electrophiles by a ubiquitous nitrogen-containing functional group, an amide. Our method uses a photoinduced catalyst system based on copper, an Earth-abundant metal. This process for asymmetric N-alkylation relies on three distinct ligands-a bisphosphine, a phenoxide and a chiral diamine. The ligands assemble in situ to form two distinct catalysts that act cooperatively a copper/bisphosphine/phenoxide complex that serves as a photocatalyst, and a chiral copper/diamine complex that catalyses enantioselective C-N bond formation. Our study thus expands enantioselective N-substitution by alkyl electrophiles beyond activated electrophiles (those bearing at least one sp- or sp2-hybridized substituent on the carbon undergoing substitution)8-13 to include unactivated electrophiles.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fotoquímica
/
Cobre
/
Amidas
Idioma:
En
Revista:
Nature
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos