Cationic organic intermediates participate in a wide variety of useful synthetic transformations, but their high reactivity can render selectivity in competing pathways difficult to control. We describe a strategy for inducing enantioselectivity in reactions of protio-iminium ions, wherein a chiral catalyst interacts with the highly reactive intermediate through a network of non-covalent interactions. This leads to an attenuation of the reactivity of the iminium ion, and allows high enantioselectivity in cycloadditions with electron-rich alkenes (the Povarov reaction). A detailed experimental and computational analysis of this catalyst system has revealed the precise nature of the catalyst-substrate interactions and the likely basis for enantioinduction.The proton (H + ) is the simplest-and arguably most versatile-catalyst for organic reactions, mediating an extraordinary range of biological and synthetic transformations (1). Although a proton cannot be rendered chiral, enantioselective Brønsted acid catalysis is attainable through the influence of the acid's conjugate base and through medium effects. The former strategy, involving use of chiral acids, has proven particularly useful as demonstrated in the design and application of chiral phosphoric acids (2,3,4), N-triflyl phosphoramides (5), aryl sulfonic acids (6), and Lewis acid-(7,8) or thiourea-assisted Brønsted acids (9,10). The use of medium effects has been less straightforward, and chiral solvents have been investigated in asymmetric catalysis with comparatively limited success (11). The recent discovery of anion-binding pathways (12,13) in reactions catalyzed by chiral small-molecule H-bond donor catalysts such as urea and thiourea derivatives (14) suggests an alternative strategy that combines elements of both approaches, wherein a chiral catalyst might associate with a protonated substrate through the counteranion, and induce enantioselectivity in additions to the cationic electrophile through specific secondary interactions with the charged species.This idea was explored in the context of the formal [4+2] cycloaddition of N-aryl imines and electron-rich olefins, also known as the Povarov reaction. (15) This Brønsted-acid catalyzed reaction affords tetrahydroquinoline derivatives with concomitant generation of up to three contiguous stereogenic centers, and enantioselective Lewis acid or phosphoric acidcatalyzed variants have been identified recently (16,17,18). The acid-catalyzed Povarov reaction between benzylidene aniline 2a and 2,3-dihydrofuran 3 was selected as a model reaction (Fig. 1A), and a broad range of chiral urea and thiourea derivatives developed and studied previously in our laboratory-as well several different Brønsted acids-were evaluated as catalysts for this transformation (Table S1, 19). Using this approach, the combination of the bifunctional sulfinamido urea derivative 1a (20) and orthonitrobenzenesulfonic acid (NBSA) was found to catalyze the model reaction with high enantioselectivity (Figs. 1B and 1C, entry 1). The im...