Organocatalytic chemo-, (E/Z)- and enantioselective formal alkenylation of indole-derived hydroxylactams using o-hydroxystyrenes as a source of alkenyl group.

The first organocatalytic asymmetric formal alkenylation of multicyclic alcohols using non-metal-based alkenes instead of alkenyl metals as a source of an alkenyl group has been established via chiral phosphoric acid catalyzed tandem reactions. This transformation directly assembles isoindolo-ß-carboline-derived hydroxylactams with o-hydroxystyrenes via an asymmetric cascade vinylogous addition/hydrogen elimination reaction sequence, offering an easy access to functionalized chiral isoindolo-ß-carbolines with one quaternary stereogenic center in high chemo-, (E/Z)-, and enantioselectivities (up to >95:5 cr, >95:5 E/Z, 97:3 er). This approach also represents the first catalytic asymmetric formal alkenylation of isoindolo-ß-carboline-derived hydroxylactams, which provides a useful strategy for functionalization of isoindolo-ß-carbolines and synthesis of chiral isoindolo-ß-carboline derivatives. In addition, the investigation on the activating mode revealed that the hydroxyl group in o-hydroxystyrene was essentially important for generating a hydrogen-bond interaction with the catalyst. The dual activation mode of hydrogen bond and ion pair between the catalyst and the substrates cooperatively facilitated the desired formal alkenylation reaction in a chemo- and stereoselective way.