Bernardi Luca, López-Cantarero Jesús, Niess Barbara, Jørgensen Karl Anker
Danish National Research Foundation, Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
J Am Chem Soc. 2007 May 2;129(17):5772-8. doi: 10.1021/ja0707097. Epub 2007 Apr 6.
The first organocatalytic enantioselective 1,6-addition of beta-ketoesters and benzophenone imine to electron-poor delta-unsubstituted dienes using cinchona alkaloids under phase-transfer conditions is demonstrated. The scope of the reaction for the beta-ketoesters is outlined for reactions with different delta-unsubstituted dienes having ketones, esters, and sulfones as electron-withdrawing substituents giving the corresponding optically active products in good yields and enantioselectivities in the range of 90-99% ee. The 1,6-addition also proceeds with a number of cyclic beta-ketoesters having different ring sizes, ring systems and substituents in high yields and enantioselectivities. The potential of this new organocatalytic 1,6-addition for beta-ketoesters is demonstrated by a two-step synthesis of the bicyclo[3.2.1]octan-8-one structure, a bicyclic bridged skeleton occurring in a variety of natural compounds. Benzophenone imines also undergo the organocatalytic asymmetric 1,6-addition to the activated dienes in high yields and with enantioselectivities from 92% to 98% ee, except in one case. The synthetic utility of this asymmetric reaction is demonstrated by the two-step transformation of the allylated alpha-amino acid derivative to highly attractive optically active pyrrolidines.
在相转移条件下，使用金鸡纳生物碱实现了β-酮酯和二苯甲酮亚胺对缺电子δ-未取代二烯的首例有机催化对映选择性1,6-加成反应。概述了β-酮酯与具有酮、酯和砜作为吸电子取代基的不同δ-未取代二烯反应的范围，反应能以良好的产率得到相应的光学活性产物，对映选择性在90 - 99% ee范围内。1,6-加成反应也能以高收率和对映选择性进行，涉及多种具有不同环大小、环系和取代基的环状β-酮酯。通过两步合成双环[3.2.1]辛-8-酮结构，证明了这种新型β-酮酯有机催化1,6-加成反应的潜力，双环桥连骨架存在于多种天然化合物中。除了一种情况外，二苯甲酮亚胺也能以高收率和92%至98% ee的对映选择性进行有机催化不对称1,6-加成至活化二烯。通过烯丙基化α-氨基酸衍生物两步转化为极具吸引力的光学活性吡咯烷，证明了这种不对称反应的合成实用性。
