Asymmetric Catalytic Double Michael Additions for the Synthesis of Spirooxindoles
40
Citation
83
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract Asymmetric cascade double Michael additions to construct 2′‐substituted 3,3′‐spirooxindoles by using a chiral guanidine organocatalyst has been developed. A series of spirooxindole derivatives containing dihydrofuran or pyrrolidine subunits were obtained with good to excellent diastereo‐ and enantioselectivities. The method showed great tolerance of a number of aromatic and aliphatic alkynones. The strategy gave access to the asymmetric synthesis of (−)‐salacin for the first time.Keywords:
Pyrrolidine
Michael reaction
Guanidine
Abstract Enantioselective desymmetrization of prochiral 1,3‐cyclodiketones is the most convenient and highly desired transformation to access densely functionalized, enantiomerically enriched scaffolds with multiple chiral centers. In recent years, organocatalysis has made significant progress in this research area along with other traditional metal‐ or enzyme‐catalyzed reactions. This mini‐review provides an overview of the recent developments in the domain of organocatalytic enantioselective desymmetrization along with a brief discussion about future perspectives.
Desymmetrization
Cite
Citations (20)
Abstract Organocatalytic methods have achieved spectacular advancements for the preparation of chiral molecules in highly enantioenriched forms. The fast development of this field can mainly be attributed to the evolution of general and reliable activation modes. The discovery and identification of new activation modes are therefore highly desirable to push the boundaries of asymmetric reactions. In this Minireview, recent advances in enantioselective carbonyl catalysis, one useful subbranch of organocatalysis for the efficient activation of simple amines, will be summarized. With elegantly designed chiral aldehyde catalysts, highly enantioselective and efficient asymmetric reactions can be developed. Continued development of enantioselective carbonyl catalysis is expected in the future.
Cite
Citations (26)
Pyrrolidine
Michael reaction
Addition reaction
Cite
Citations (13)
The enantioselective desymmetrization is regarded as an effective strategy for producing chiral compounds from achiral substrates. The past decade saw the establishment of organocatalysis in organic synthesis and also organocatalytic desymmetrizations have emerged in recent years. In particular, bifunctional organocatalysts have shown the ability to promote enantioselective desymmetrizations enabling simultaneous covalent and/or non-covalent activations of the reagents. Many classes of prochiral and meso compounds were efficiently desymmetrized, being cyclic anhydrides ringopening and diols acylation the most widely employed transformations. The goal of this review is to give a comprehensive overview on the developed strategies in the field of the enantioselective desymmetrizations promoted by bifunctional organocatalysts. Keywords: Bifunctional activation, desymmetrization, enantioselectivity, meso compound, organocatalysis, prochiral substrate.
Desymmetrization
Organic Synthesis
Cite
Citations (20)
Abstract The first use of phosphahelicene in enantioselective organocatalysis is reported. New chiral phosphahelicenes have been prepared and enable highly enantioselective [3+2] cyclization reactions between arylidene‐ or alkylidenemalononitriles and γ‐substituted allenoates or cyanoallenes. These reactions afford cyclopentene derivatives in both high yields and diastereoselectivities, with enantiomeric excesses of up to 97 %.
Cyclopentene
Cite
Citations (37)
Pyrrolidine
Michael reaction
Azole
Conjugate
Cite
Citations (2)
Abstract Organocatalytic methods have achieved spectacular advancements for the preparation of chiral molecules in highly enantioenriched forms. The fast development of this field can mainly be attributed to the evolution of general and reliable activation modes. The discovery and identification of new activation modes are therefore highly desirable to push the boundaries of asymmetric reactions. In this Minireview, recent advances in enantioselective carbonyl catalysis, one useful subbranch of organocatalysis for the efficient activation of simple amines, will be summarized. With elegantly designed chiral aldehyde catalysts, highly enantioselective and efficient asymmetric reactions can be developed. Continued development of enantioselective carbonyl catalysis is expected in the future.
Cite
Citations (95)
Simple pyrrolidine-azole conjugates have been synthesized and found to be efficient catalysts for asymmetric Michael addition to nitrostyrenes. The identified optimal catalysts, pyrrolidine-azoles 2, 8 and 13, could catalyze the asymmetric Michael addition of a range of Michael donors and nitrostyrenes in high yields (up to 99%) and excellent stereoselectivities (up to 99:1 dr and 97% ee).
Pyrrolidine
Michael reaction
Azole
Conjugate
Cite
Citations (0)
l-(3,3,3-Trifluoro-l-propenylsulfonyl)pyrrolidine 1 was synthesized from N-mesylpyrrolidine and ethyl trifluoroacetate.Michael addition of 1 with some selected nucleophiles including enolate anions and an amine gave the adducts regioselectively in high yields (58-100 %), although no adducts with organometallics were obtained.Much attention has been addressed to trifluoromethylated compounds because they often exhibit unique biological activities (1).For introduction of the trifluoromethyl group into a carbon skeleton, the use of a proper building block, which already has the trifluoromethyl group in it, is one of the most efficient approaches (2).From this point of view, we are interested in the use of trifluoropropenylsulfonyl compounds for the synthesis of trifluoromethylated compounds (3).Some organic compounds containing the trifluoropropenyl group also exhibit remarkable pharmaceutical activities (4).In this paper, we wish to report the synthesis of l-(3,3,3trifluoro-l-propenylsulfonyl)pyrrolidine 1 as a new class of trifluoromethylated building blocks and the Michael addition of 1 with some selected nucleophiles.
Pyrrolidine
Michael reaction
Cite
Citations (5)
Zhong and co-workers report the application of the new pyrrolidine-based organocatalyst 3 in the asymmetric Michael addition of six-membered cyclic ketones 1 to (hetero)aromatic nitroolefins 2 giving the corresponding Michael adducts 4 in high yields (87-99%) along with excellent diastereo- and enantioselectivities (98:2 to >99:1 dr, 96:4 to >99.5:0.5 er). The strong polar P=O group of catalyst 3 is attributed to play a significant role. As supported by DFT calculations, it likely orientates the nitro group for the stereoselective enamine addition via a strong H-bond mediated by water.
Pyrrolidine
Michael reaction
Enamine
Cite
Citations (0)