Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis.
Sci Adv
; 9(24): eadg7754, 2023 Jun 16.
Article
em En
| MEDLINE
| ID: mdl-37327329
ABSTRACT
Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products and medicinally relevant molecules. Nevertheless, general and broadly applicable methods for enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to the easy racemization. Here, we report a visible light photoactivation and phosphoric acid-catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, and Hantzsch ester for the expeditious synthesis of α,α-diarylketones with excellent yields and enantioselectivities. In the reaction, three chemical bonds, including CâO, CâC, and CâH, are formed, providing a de novo synthesis reaction for chiral α,α-diarylketones. Moreover, this protocol provides a convenient and practical method to synthesize or modify complex bioactive molecules, including efficient routes to florylpicoxamid and BRL-15572 analogs. Computational mechanistic studies revealed that C-H/π interactions, π-π interaction, and the substituents of Hantzsch ester all play crucial roles in the stereocontrol of the reaction.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ésteres
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Cetonas
Tipo de estudo:
Guideline
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2023
Tipo de documento:
Article