Enantioselective organocatalytic formal [3+2]-cycloaddition of isatin-derived ketimines with benzylidenemalononitriles and benzylidineindanones

Abstract

Electron-deficient alkenes undergo organocatalysed formal [3+2]-cycloaddition with isatin-derived imines, generating complex spirocyclic products with high yield and stereoselectivity.

Stereoselective synthesis of CF3-containing spirocyclic-oxindoles using N-2,2,2-trifluoroethylisatin ketimines: an update

“…A highly efficient enantioselective approach for expedient access to a broad variety of CF 3 -embedded spirocyclic oxindoles having four contiguous stereocenters via a formal [3+2] cycloaddition sequence was realized by Knipe and co-workers ( Scheme 10 ). 58 By employing 10 mol% of cinchona-derived thiourea C-5 as the chiral organocatalyst, the respective products 22 derived from N -2,2,2-trifluoroethylisatin ketimines 1 and activated alkene dipolarophiles 21 have been achieved in 67–98% yield with excellent diastereoselectivity and moderate to outstanding enantioselectivity. Overall, 15 compounds comprising varied substitutions were constructed with identical conditions.…”

Recent Advances of N-2,2,2-Trifluoroethylisatin Ketimines in Organic Synthesis

“…In 2021, Knipe and co-workers established the organocatalytic asymmetric [3 + 2] cycloaddition of N -2,2,2-trifluoroethylisatin ketimines 1 with benzylidenemalononitriles 56 catalyzed by a cinchona-derived thiourea catalyst C24 ( Scheme 22 ) [ 39 ]. Under mild conditions, this reaction can provide a series of functionalized spiro-pyrrolidinoxindole derivatives with three to four chiral centers in high yields (67–98%) with good diastereo- and enantioselectivities (2:1–>100:1 dr and 73–97% ee).…”

Recent Progress on the [3+2] Cycloaddition Route for the Synthesis of All-Carbon Quaternary Stereocentres

“…Some of the examples reported contained molecules with all-carbon quaternary stereocentres, as exemplified in the synthesis of 45 and 47 (Scheme 13 ). 30…”