| The organocatalytic direct asymmetric Michael reaction as one of the most powerful and efficient methods for the formation of carbon-carbon bonds in organic synthesis has attracted great attention in the past decades. Recently, with the scope of this field rapidly expanding, Many enantioselective Michael reactions of malonates, adehydes and ketones to nitroalkenes using chiral organocatalysts have been reported. Nevertheless, the Michael reaction of acyclic ketones with nitroalkenes has proven to be a formidable challenge. Barbas and List respectively reported the first organocatalytic Michael addition of ketones to nitroalkenes using L-proline as a catalyst, then Alexakis et al. described 2,2'-bipyrrolidine effectively catalyzed the asymmetric Michael addition reactions ofα-hydroxyketones to nitroalkenes. Although several different systems for this type of transformation that rely on chiral organocatalysts have been developed to date, Tsogoeva and Jacobsen independently have shown that chiral primary amine-thiourea could serve as very efficient chiral organocatalysts for conjugate addition reactions of acyclic aliphatic ketones to nitroalkenes.In the past few years, although the organocatalytic direct asymmetric Michael reaction of unmodified ketones to nitroalkenes has been investigated intensely, the reaction of functionalized ketones is a much less developed field, such asα-phenylthioacetone, which contain a very useful phenylthio group. The use of this functional group in Pummerer reaction is the important methodology for the synthesis of heterocyclic compounds, and this functional group can be further transformed into other versatile functionalities, such as carbonyl functionality ( direct oxidative desulfuration ) and sulfonyl functionality. Furthermore, the use of sulfonyl functionality as an auxiliary group is a very useful synthetic strategy due to this functional group can act as an electron-withdrawing group or as a leaving group and can be substituted by an alkyl group, a carbonyl functionality or a nucleophile as well as undergo aβ-elimination process.We report herein the first asymmetric organocatalyztic conjugate addition of thioacetones to nitroalkenes, which furnished the corresponding highly functionalizedγ-nitro carbonyl compounds. Undoubtedly, the functional thio groups will dramatically functionalizeγ-nitro carbonyl compounds and broaden the application of chiral nitroalkanes in organic synthesis.The asymmetric additions of thioacetones to nitroalkenes afforded the corresponding adducts in moderate to good yields with up to 96% ee and 20:80 dr (syn: anti). The addition of thioacetones to aromatic nitroalkenes obtained the desired products with good enantioselectivity when aromatic nitroalkenes have either electron donating or electron withdrawing substituents under the optimized condition. The configuration reversal might take place when the further oxidated products were treated with LiHMDS, affording sole anti-diastereoselective products.1). Although the organocatalytic direct asymmetric Michael reaction of unmodified ketones to nitroalkenes has been investigated intensely, the reaction of functionalized ketones is a much less developed field. In this paper, we report the first organocatalytic conjugate addition of thioethers to nitroalkenes.2). Because of the ability to further transform the nitro group and phenylthio group into other useful functionalities,γ-nitro carbonyl compounds, which contain the two useful functional groups of nitro and phenylthio as the Michael adducts will be more useful and versatile in organic synthesis.3). Under mild condition, highly functionalizedγ-nitro ketones formed successfully with high ees and good yields.4). The configuration reversal might take place when the further oxidated products were treated with LiHMDS, affording sole anti-diastereoselective products. We first report the application of the sterically-hindered lithium amide base in the configuration reversal of the chiral compounds.
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