The development of sustainable processes is one of the main priorities for preparative chemistry in the 21st century.[1] For several decades, a large effort has been devoted to the development of new, efficient catalytic transformations to achieve high molecular complexity from simple starting materials. Consequently, the combination of very efficient catalytic methods (e.g., organocatalysis [2] and gold catalysis [3] ) in a tandem or one-pot process [4] should provide a powerful tool for saving both energy and resources. These two powerful methodologies have already been used in total synthesis, although at different steps of the synthesis.[5]The asymmetric conjugate addition of aldehydes to nitroolefins catalyzed by a pyrrolidine derivative is an efficient method for the synthesis of g-nitrocarbonyl building blocks.[6] Among various nitroolefins, b-nitrostyrenes are the most widely used because of their possible conversion into substituted pyrrolidines, [7] butyrolactones, [8] or cyclopentanes.[9] Other functionalized nitroolefins [10] have also been used, and some of them applied in target-oriented synthesis.[11] However, in all cases, the synthesis of the nitrocarbonyl compounds and their subsequent conversions were carried out in a sequential way. Knowing the compatibility of amines and gold catalysts, [12] and our recent results on 1,4-additions of aldehydes to nitrodienes, [13] as well as goldcatalyzed transformations of functionalized alkynes, [14] we envisaged a one-pot process consisting of an enantioselective organocatalytic Michael addition of aldehydes 1 to nitroenyne 2, and a subsequent gold-catalyzed tandem acetalization/cyclization of the corresponding adduct 3 by electrophilic activation [3] of the triple bond. Herein we disclose our results on this one-pot reaction which leads to nitro-substituted tetrahydrofuranyl ethers 4 with high diastereo-and enantioselectivities (Scheme 1).First, we optimized the organocatalyzed conjugate addition of isovaleraldehyde (1 a) to the phenyl-substituted nitroenyne 2 a in the presence of diphenylprolinol silyl ether 5. The best conditions appeared to be 10 equivalents of aldehyde in the presence of 10 mol % of organocatalyst 5 at À10 8C [Eq. (1) in Scheme 2 and see the Supporting Information].Then we investigated the gold-catalyzed tandem acetalization/cyclization of the aldehyde 3 a into the expected tetrahydrofuranyl ether 4 a in the presence of various gold sources and additives. After optimization, we carried out the reaction in presence of [PPh 3 Au]Cl and AgBF 4 with 10 mol % of p-TsOH and only 1.2 equivalents of ethanol in chloroform at 0 8C, and observed the best diastereoselectivity. [Eq. (2) in Scheme 2 and see the Supporting Information].Having optimized both catalysts and the reaction conditions, we next examined the tandem acetalization/cyclization on the model substrate 3 a in the presence of various alcohols (Scheme 3). Pleasingly, the reaction tolerates a wide range of primary and secondary alcohols and afforded the expected tetrahydrofuran 4...

Enantioselective One-Pot Organocatalytic Michael Addition/Gold-Catalyzed Tandem Acetalization/Cyclization. -Although some asymmetric gold-catalyzed cyclizations are known using either chiral ligands or chiral anions, a third alternative strategy is developed consisting of an enantioselective organocatalytic Michael addition to a nitroenyne (II) and a subsequent gold-catalyzed acetalization/cyclization. Organocatalysis and gold catalysis are shown to be compatible and complementary in a one-pot process, thereby enabling isolation of the products in higher yields relative to those for the sequential reaction. -(BELOT, S.; VOGT, K. A.; BESNARD, C.; KRAUSE*, N.; ALEXAKIS, A.; Angew.

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