Asymmetric [4 + 2] Annulation Reactions Catalyzed by a Robust, Immobilized Isothiourea

A polystyrene-supported
isothiourea (1a) behaves as
a highly efficient organocatalyst in a variety of formal [4 + 2] cycloaddition
reactions. The catalytic system has proven to be highly versatile,
leading to six-membered heterocycles and spiro-heterocycles bearing
an oxindole moiety in high yields and very high enantioselectivities
(32 examples, including the previously unreported oxindole spiropyranopyrazolones 8; 97% mean ee). The notable chemical stability of 1a under operation conditions results in high recyclability (11 cycles,
accumulated TON of 76.8) and allows the implementation of an extended-operation
continuous flow process (no decrease in yield or ee after 18 h).