Li J, Cai Y, Chen W, Liu X, Lin L, Feng X * Sichuan University, Chengdu, P. R. of China
Highly Enantioselective Fluorination of Unprotected 3-Substituted Oxindoles: One-Step Synthesis of BMS 204352 (Maxipost).
J. Org. Chem. 2012;
77: 9148-9155
Key words
maxipost - asymmetric fluorination - scandium triflate -
N-fluorobenzenesulfonimide
Significance
Maxipost is a post-stroke neuroprotective agent that acts by opening large conductance Ca2+-activated (maxi-K) potassium channels. Previous syntheses of maxipost by asymmetric fluorination of oxindoles required protection of the oxindole nitrogen as the N-Boc derivative. The route depicted features the direct asymmetric catalytic fluorination of the oxindole A using N-fluorobenzenesulfinimide (B) in the presence of 10 mol% of a chiral complex derived from scandium triflate and the amine oxide ligand C.
Comment
Attempts to perform the maxipost synthesis on a 3.5 mmol scale resulted in decreased yield and enantioselectivity (53% yield, 86% ee) due to the low solubility of the substrate. By constrast, the asymmetric fluorinaton of oxindole D on a 4.0 mmol scale gave E in 93% yield and 97% ee. The small selection of the 29 examples described, showed that yields and enantioselectivities are generally high.
