Regio- and Enantioselective Synthesis of Azole Hemiaminal Esters by Lewis Base Catalyzed Dynamic Kinetic Resolution.
J Am Chem Soc
; 138(14): 4818-23, 2016 Apr 13.
Article
en En
| MEDLINE
| ID: mdl-27003237
ABSTRACT
We report a modular three-component dynamic kinetic resolution (DKR) that affords enantiomerically enriched hemiaminal esters derived from azoles and aldehydes. The novel and scalable reaction can be used to synthesize valuable substituted azoles in a regioselective manner by capping (e.g., acylation) of the equilibrating azole-aldehyde adduct. With the use of a prolinol-derived DMAP catalyst as the chiral Lewis base, the products can be obtained in high chemical yield and with high enantiomeric excess. The DKR was performed on a multikilogram scale to produce a tetrazole prodrug fragment for a leading clinical candidate that posed formidable synthesis challenges.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Azoles
/
Ésteres
/
Bases de Lewis
Idioma:
En
Revista:
J Am Chem Soc
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos