Organocatalytic Asymmetric Direct -Alkynylation of Cyclic g src="http://pubs.acs.org/images/gifchars/beta2.gif" border="0" align=

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• 作者：Thomas B. Poulsen ; Luca Bernardi ; José ; Alem&aacute ; n ; Jacob Overgaard ; Karl Anker Jg src="http ; //pubs.acs.org/images/gifchars/oslash.gif" border="0">rgensen
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：January 17, 2007
• 年：2007
• 卷：129
• 期：2
• 页码：441 - 449
• 全文大小：250K
• 年卷期：v.129,no.2(January 17, 2007)
• ISSN：1520-5126

文摘

The first organocatalytic enantioselective direct ges/gifchars/alpha.gif" BORDER=0>-alkynylation of ges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-ketoesters and 3-acyl oxindolesis described. It is demonstrated that activated ges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-halo-alkynes undergo nucleophilic acetylenic substitutioncatalyzed by chiral phase-transfer compounds to afford the alkynylated products in high yields and excellentenantioselectivities. The potential of the reaction is first demonstrated for various alkynylating reagentshaving 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 innucleophile is demonstrated for a large number of cyclic ges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-ketoesters with various ring-sizes and for oxindolesas well. The corresponding optically active products are formed in high yields and with enantioselectivitiesup to 98% ee. The procedure allows for the stereocontrolled attachment of an ethynyl unit in the ges/gifchars/alpha.gif" BORDER=0>-positionto the carbonyl compound by facile removal of the activating group, and this has been demonstrated for anumber of the optically active allyl esters. Furthermore, the synthesis of optically active 1,4-enynes is alsoshown. The isolation and characterization by X-ray analysis of the catalyst with p-nitrophenolate as thecounterion allowed us to propose a model of the catalyst-substrate intermediate which might account forthe observed enantioselectivity of the organocatalytic enantioselective ges/gifchars/alpha.gif" BORDER=0>-alkynylation reaction. Furthermore,it is suggested that this intermediate is also the reactive species for a number of other electrophiles addingto ges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-ketoesters giving enantioselectivities in the range of 90-98% ee.