Zinc catalyzed and mediated asymmetric propargylation of trifluoromethyl ketones with a propargyl boronate.
J Org Chem
; 78(8): 3592-615, 2013 Apr 19.
Article
em En
| MEDLINE
| ID: mdl-23544787
ABSTRACT
The development of zinc-mediated and -catalyzed asymmetric propargylations of trifluoromethyl ketones with a propargyl borolane and the N-isopropyl-l-proline ligand is presented. The methodology provided moderate to high stereoselectivity and was successfully applied on a multikilogram scale for the synthesis of the Glucocorticoid agonist BI 653048. A mechanism for the boron-zinc exchange with a propargyl borolane is proposed and supported by modeling at the density functional level of theory. A water acceleration effect on the zinc-catalyzed propargylation was discovered, which enabled a catalytic process to be achieved. Reaction progress analysis supports a predominately rate limiting exchange for the zinc-catalyzed propargylation. A catalytic amount of water is proposed to generate an intermediate that catalyzes the exchange, thereby facilitating the reaction with trifluoromethyl ketones.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pargilina
/
Zinco
/
Ácidos Borônicos
/
Prolina
/
Hidrocarbonetos Fluorados
/
Cetonas
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article