Synthesis of 9-amino(9-deoxy)epi cinchona alkaloids, general chiral organocatalysts for the stereoselective functionalization of carbonyl compounds.
Nat Protoc
; 8(2): 325-44, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23329005
ABSTRACT
We describe two procedures for the synthesis of primary amines derived from 9-amino(9-deoxy)epi cinchona alkaloids, valuable catalysts used in the asymmetric functionalization of carbonyl compounds. The first approach allows the one-pot 5-g-scale syntheses of four cinchona-based analogs (1, 3, 5 and 7) from the alkaloids quinine (QN), quinidine (QD), dihydroquinine (DHQN) and dihydroquinidine (DHQD), respectively, performed by means of a Mitsunobu reaction to introduce an azide group, followed by reduction and hydrolysis. Demethylation of 1, 3, 5 and 7 with BBr(3) provided direct access to the bifunctional aminocatalysts 2, 4, 6 and 8. A second approach, more convenient for scale-up (tested to a 20-g scale), is also provided. In this second procedure, the azides, formed from the O-mesylated derivatives of QN and QD, are selectively reduced with LiAlH(4) to afford catalysts 1 and 3, whereas hydrogenation (Pd/C) provides 5 and 7. Demethylation of 1, 3, 5 and 7 using an alkylthiolate affords 2, 4, 6 and 8 in a process in which the less-expensive QN and QD are the only starting materials used.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Alcaloides de Cinchona
/
Técnicas de Química Sintética
Idioma:
En
Revista:
Nat Protoc
Año:
2013
Tipo del documento:
Article
País de afiliación:
España