Zinc catalyzed and mediated asymmetric propargylation of trifluoromethyl ketones with a propargyl boronate.
J Org Chem
; 78(8): 3592-615, 2013 Apr 19.
Article
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pargyline
/
Zinc
/
Boronic Acids
/
Proline
/
Hydrocarbons, Fluorinated
/
Ketones
Language:
En
Journal:
J Org Chem
Year:
2013
Document type:
Article
Affiliation country: