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Organocatalytic Chemo‑, (E/Z)- and Enantioselective Formal Alkenylation of Indole-Derived Hydroxylactams Using o‑Hydroxystyrenes as a Source of Alkenyl Group

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journal contribution
posted on 2014-08-01, 00:00 authored by Hong-Hao Zhang, Yue-Ming Wang, Yuan-Wei Xie, Zi-Qi Zhu, Feng Shi, Shu-Jiang Tu
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-β-carboline-derived hydroxylactams with o-hydroxystyrenes via an asymmetric cascade vinylogous addition/hydrogen elimination reaction sequence, offering an easy access to functionalized chiral isoindolo-β-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-β-carboline-derived hydroxylactams, which provides a useful strategy for functionalization of isoindolo-β-carbolines and synthesis of chiral isoindolo-β-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.