The asymmetric Povarov reaction of N-arylimines with 2- and 3-vinylindoles has been developed using a chiral phosphoric acid ((S)-TRIP) as catalyst. The peculiar reactivity of vinylindoles allowed also the disclosure of a Povarov Friedel-Crafts sequence, and the trapping of the reaction intermediate with nucleophilic species, thus providing a versatile platform for the preparation of highly enantioenriched indole derivatives.

Abstract:The first catalytic asymmetric PictetSpengler reaction of isatins is presented. BINOLderived phosphoric acids were found to be competent catalysts for this transformation, giving challenging spirooxindole structures bearing a quaternary stereocentre with generally good results. The 1,2,3,4-tetrahydro-b-carboline products (spiroindol-

A catalytic asymmetric addition of nitroalkanes to alkylideneindolenines, generated in situ from arylsulfonylindoles, is presented. Despite the weakness of the non-covalent H-bond interactions between catalyst and substrates, the performance of the bifunctional organocatalyst used was found to be essentially unaffected by the polarity of the reaction medium. Nitroalkanes, mostly used in nearly stoichiometric amounts, could thus function both as sol-vents and reagents, resulting in a truly solvent-free reaction. The broad substrate scope shown by the present transformation allowed the preparation of some optically active tryptamine precursors that are not accessible through the previous catalytic asymmetric methods.

Optically active β-amino-α-methylene carbonyl derivatives (aza-Morita−Baylis−Hillman adducts) were prepared using a one-pot protocol involving an enantioselective Mannich reaction catalyzed by various quinine-based catalysts, followed by a Horner olefination.

The first catalytic asymmetric Wittig reaction is presented. Hydrogen-bond donors catalyze the [2+2] cycloaddition reaction between stabilized phosphorus ylides and 4-substituted cyclohexanones, breaking their symmetry plane and furnishing axially chiral olefins with moderate stereoselectivities.Asymmetric organocatalysis has witnessed spectacular advances over the last few years. 1 Transmission of the chiral information from catalyst to substrate has been achieved with high fidelity in an impressive range of chemical transformations. In most cases, the result of these efficient asymmetric protocols is the stereocontrolled formation of a chiral center, typically a tetrahedral carbon atom bearing four different substituents. Also kinetic resolutions, wherein the catalyst distinguishes two enantiomeric substrates and desymmetrization processes, wherein the catalyst recognizes local asymmetry, discriminating two enantiotopic moieties, have been studied in detail. In these latter cases, substrate/product asymmetry is again mostly due to tetrahedral carbon atoms. However, chirality is not restricted to the presence of a chiral center. 2 Compounds featuring a chirality axis or plane are in fact of tremendous importance. Axial/planar chirality is showcased in many natural compounds, 3 ligands or catalysts for asymmetric synthesis, 4 synthetic intermediates, 5 and molecular switches/motors. 6 Use of organocatalysis for the stereocontrolled generation of chiral axes or planes has, however, been largely ignored. 7Herein, we present the first example of a catalytic asymmetric Wittig reaction (Scheme 1). The reaction furnishes enantioenriched axially chiral olefins 3 and is catalyzed by hydrogen-bond donors. The Wittig 8 olefination between carbonyl compounds and phosphorus ylides, together with its related counterparts (Horner 9 involving phosphine oxides and Horner-Wadsworth-Emmons 10 involving phosphonates), is amongst the most venerable transformations of organic chemistry. These powerful methods for C=C bond formation have found ubiquitous applications in organic synthesis, 11 including preparations of axially chiral olefins. 12 Scheme 1 Asymmetric olefination of ketones 1Olefination of a ketone featuring a symmetry plane but lacking a symmetry axis leads in fact to an axially chiral alkene, as exemplified in Scheme 1 for the benchmark reaction for asymmetric Wittig-type processes, with 4-substituted cyclohexanones 1. 13 Stereoselectivity in this class of symmetry-breaking transformations has been achieved in the past using Wittig and related olefinations, exploiting stoichiometric chiral auxiliaries and reagents. 13,14 A single example instead made use of a chiral catalyst. 15,16 Horner-Wadsworth-Emmons olefination of 4-tert-butylcyclohexanone (1a), performed under phase-transfercatalysis conditions, gave the corresponding olefin in only moderate enantioselectivity (<57% ee). We tentatively ascribed this moderate stereocontrol to the reversibility of the first step in Horner-Wadsworth-Emmons reactions. 11a We thus set...