An Organocatalytic Asymmetric Friedel–Crafts Addition/Fluorination Sequence: Construction of Oxindole–Pyrazolone Conjugates Bearing Vicinal Tetrasubstituted Stereocenters

A highly efficient
and practical one-pot sequential process, consisting
of an organocatalytic enantioselective Friedel–Crafts-type
addition of 4-nonsubstituted pyrazolones to isatin-derived N-Boc ketimines and a subsequent diastereoselective fluorination
of the pyrazolone moiety, is developed. This reaction sequence delivers
novel oxindole–pyrazolone adducts featuring vicinal tetrasubstituted
stereocenters with a 0.5 mol % catalyst loading in high yield with
excellent enantio- and diastereocontrol. Notably, chloro, bromo, and
thioether functionalities can be readily incorporated, rendering a
broad diversity of the product.