- Enantioselective Michael Reaction of Cyclic β-Ketoesters with Morita-Baylis-Hillman Derivatives Using a Phase-Transfer Catalyst
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This study aims to develop a highly enantioselective Michael reaction of cyclic β-ketoesters with Morita-Baylis-Hillman (MBH) derivatives using a phase-transfer catalyst. Cyclic β-ketoesters reacted with MBH derivatives to stereoselectively generate a quaternary carbon center in the presence of cinchona alkaloid-derived bulky ammonium catalyst, and aqueous KOH and Michael adducts bearing an acrylate moiety were obtained in good chemical yields with good enantioselectivity.
- Takagi, Ryukichi,Fujii, Emi,Kondo, Hirotoshi
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p. 11191 - 11203
(2018/09/12)
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- Organocatalytic asymmetric direct α-alkynylation of cyclic β-ketoesters
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The first organocatalytic enantioselective direct α-alkynylation of β-ketoesters and 3-acyl oxindoles is described. It is demonstrated that activated β-halo-alkynes undergo nucleophilic acetylenic substitution catalyzed by chiral phase-transfer compounds to afford the alkynylated products in high yields and excellent enantioselectivities. The potential of the reaction is first demonstrated for various alkynylating reagents having chloride and bromide as the leaving groups and substituents such as allyl and alkyl esters, amides, ketones, and sulfones. These reactions proceed with 74-99% yield and 88-97% ee. Then the scope in nucleophile is demonstrated for a large number of cyclic β-ketoesters with various ring-sizes and for oxindoles as well. The corresponding optically active products are formed in high yields and with enantioselectivities up to 98% ee. The procedure allows for the stereocontrolled attachment of an ethynyl unit in the α-position to the carbonyl compound by facile removal of the activating group, and this has been demonstrated for a number of the optically active allyl esters. Furthermore, the synthesis of optically active 1,4-enynes is also shown. The isolation and characterization by X-ray analysis of the catalyst with p-nitrophenolate as the counterion allowed us to propose a model of the catalyst-substrate intermediate which might account for the observed enantioselectivity of the organocatalytic enantioselective α-alkynylation reaction. Furthermore, it is suggested that this intermediate is also the reactive species for a number of other electrophiles adding to β-ketoesters giving enantioselectivities in the range of 90-98% ee.
- Poulsen, Thomas B.,Bernardi, Luca,Aleman, Jose,Overgaard, Jacob,Jorgensen, Karl Anker
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p. 441 - 449
(2007/10/03)
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