Highly enantioselective aza-Baylis-Hillman reactions catalyzed by chiral thiourea derivatives

被引:165
作者
Raheem, IT [1 ]
Jacobsen, EN [1 ]
机构
[1] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA
关键词
asymmetric catalysis; aza-Baylis-Hillman reaction; kinetic isotope effect; organocatalysis; thiourea catalyst;
D O I
10.1002/adsc.200505230
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
We report the discovery of asymmetric aza-Baylis-Hillman (ABH) reactions of N-p-nitrobenzenesulfonylimines with methyl acrylate catalyzed by chiral thiourea derivatives. A series of aromatic imines was found to undergo coupling with methyl acrylate with unprecedented levels of enantioselectivity (87-99% ee), albeit only in modest (25-49%) yields. A DABCO-acrylate-imine adduct was isolated as a key intermediate in the ABH reaction. We provide a mechanistic analysis based on the identity of this intermediate as well as kinetic investigations and isotope studies, and propose a rationale for the observed limitations in yield. Synthetic applications of the ABH products are also described.
引用
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页码:1701 / 1708
页数:8
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