Wang X, Yang T, Cheng X, Shen Q * Shanghai Institute of Organic Chemistry, P. R. of China and Oak Ridge National Laboratory, USA
Enantioselective Electrophilic Trifluoromethylthiolation of β-Ketoesters: A Case of Reactivity and Selectivity Bias for Organocatalysis.
Angew. Chem. Int. Ed. 2013;
52: 12860-12864
Key words
trifluoromethylthio-lation - β-keto esters - quinine
Significance
A highly enantioselective trifluoromethylthiolation of β-keto esters is reported by Shen and co-workers. The reaction is catalyzed by quinine 1 or the quinine-derived phase-transfer catalyst 2. Good to excellent yields and enantioselectivities are obtained by utilizing different catalysts for different ring sizes of the β-keto esters. The free hydroxyl group of the catalyst is crucial for reactivity, and the SCF3-substituted quaternary ammonium pathway was ruled out by control experiments. The proposed reaction pathway involves a dual activation, in which the catalyst activates both the β-keto ester and the SCF3 reagent via a double hydrogen bonding.
Comment
The introduction of fluorine functional groups into different molecules is of great importance for the pharmaceutical and agrochemical industries. Here, the authors report a practical procedure for highly enantioselective trifluoromethylthiolation of β-keto esters. This methodology provides a straightforward way to build quaternary carbon centers with a SCF3 group, which potentially could lead to useful drug candidates. At the same time, Rueping and co-workers report a very similar study, but utilizing different SCF3 sources (T. Bootwicha, X. Liu, R. Pluta, I. Atodiresei, M. Rueping Angew. Chem. Int. Ed. 2013, 52, 12856).
