Computational study-led organocatalyst design: A novel, highly active urea-based catalyst for addition reactions to epoxides
Computational study-led organocatalyst design: A novel, highly active urea-based catalyst for addition reactions to epoxides
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DOI：
10.1021/jo702154m
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发表时间：
2008-02-01
影响因子：
3.6
通讯作者：
Connon, Stephen J.
中科院分区：
文献类型：
--
作者：
Fleming, Eimear M.;Quigley, Cormac;Connon, Stephen J.
[图表]一项计算机研究检查了简单硫脲催化剂和三种不同亲电子试剂之间氢键配合物的稳定性，并确定了一种新型、高活性的 N-甲苯磺酰脲催化剂，用于促进环氧化物亲电子试剂的加成反应。 6的合成和评估表明，在简单的N,N-双芳基脲和硫脲（包括1）不活泼的条件下，它是1,2-二甲基吲哚与氧化苯乙烯加成的强大催化剂。随后的研究确定 6 与一系列吲哚和环氧化物底物（包括（E）-二苯乙烯氧化物）相容，并发现相对较差的亲核试剂，例如空间和电子失活的苯胺、苯硫酚和苯甲醇，可以在温和条件下有效且区域选择性地添加到环氧乙烷中。
[GRAPHICS]An in silico study examined the stabilities of hydrogen-bonded complexes between simple thiourea catalysts and three different electrophiles and identified a novel, highly active N-tosyl urea catalyst for the promotion of addition reactions to epoxide electrophiles. Synthesis and evaluation of 6 revealed it to be a powerful catalyst for the addition of 1,2-dimethylindole to styrene oxide under conditions in which simple N,N-bis-aryl ureas and thioureas (including 1) are inactive. Subsequent studies determined 6 to be compatible with a range of indole and epoxide substrates (including (E)-stilbene oxide) and found that relatively poor nucleophiles such as sterically and electronically deactivated anilines, thiophenol, and benzyl alcohol could be efficiently and regioselectively added to oxiranes under mild conditions.