Squaramide-catalyzed domino Michael/aza-Henry [3 + 2] cycloaddition: asymmetric synthesis of functionalized 5-trifluoromethyl and 3-nitro substituted pyrrolidines

Abstract

The diastereo- and enantioselective Michael/aza-Henry [3 + 2] cycloaddition reaction of trifluoromethyl-substituted iminomalonate and nitroalkenes has been developed employing 10 mol% of a quinine-squaramide catalyst. A series of highly functionlized 5-trifluoromethyl and 3-nitro substituted pyrrolidine derivatives containing three contiguous stereogenic centers are efficiently prepared with very good yields and excellent stereoselectivities (up to 82% yield, >20 : 1 dr, and 99% ee).