Combining cycloisomerization with trienamine catalysis: a regiochemically flexible enantio- and diastereoselective synthesis of hexahydroindolesElectronic supplementary information (ESI) available: Experimental procedures, characterization for novel compounds, stereochemical assignment of cycloadducts, copies of 1H and 13C NMR spectra and HPLC traces. See DOI: 10.1039/c5cc08886k

• Main Authors: Chintalapudi, V, Galvin, E. A, Greenaway, R. L, Anderson, E. A
• Format: Article
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/c5cc08886k

The synthesis of polysubstituted hexahydroindoles through trienamine-organocatalyzed cycloadditions of pyrrolidinyl dienals, prepared by palladium-catalyzed cycloisomerization, is reported. The cycloadditions of this novel class of dienals proceed with excellent levels of enantio- and diastereoselectivity, with the regioselectivity of cycloaddition with respect to the tethering ring readily tuned through design of the cycloisomerization substrate. This work culminates in the first examples of double-stereodifferentiating trienamine catalysis, where catalyst stereocontrol dominates facial selectivity in the cycloaddition, affording azacyclic products that are specifically functionalized at every position. The synthesis of polysubstituted hexahydroindoles through trienamine-organocatalyzed cycloadditions of pyrrolidinyl dienals, prepared by palladium-catalyzed cycloisomerization, is reported.