Wolf Florian F, Klare Helge, Goldfuss Bernd
Institut für Organische Chemie, Universität zu Köln , Greinstrasse 4, 50939 Köln, Germany.
J Org Chem. 2016 Mar 4;81(5):1762-8. doi: 10.1021/acs.joc.5b02167. Epub 2016 Feb 12.
Enantioselective Michael additions of 4-hydroxycoumarin to β-nitrostyrenes are catalyzed by different chiral, bifunctional hydrogen-bonding catalysts, based on thiourea- and squaramide motifs. The scope of the catalysis is tested by employing a series of substituted β-nitrostyrenes as well as different solvents. The 3,5-bis(trifluoromethyl)phenyl- and quinine-substituted squaramide catalyst is shown to be the most selective catalyst, resulting in 78% yield and 81% ee. Computational analyses of transition structures with different binding modes show that the most favored transition structure exhibits squaramide (NH)2 binding to an oxygen atom of the enolate nucleophile, while the nitroalkene coordinates via hydrogen bonding to the ammonium function of the quinuclidine unit of the catalyst. Hence, the canted directionality of the squaramide (NH)2 motif, favoring one-atom binding, might be decisive for the selectivity of the reaction. The absolute configuration of the major (-)-(R) enantiomer of the product is assigned computationally according to its optical rotation.
基于硫脲和方酰胺基序的不同手性双功能氢键催化剂可催化4-羟基香豆素与β-硝基苯乙烯的对映选择性迈克尔加成反应。通过使用一系列取代的β-硝基苯乙烯以及不同的溶剂来测试催化反应的范围。结果表明，3,5-双（三氟甲基）苯基和奎宁取代的方酰胺催化剂是最具选择性的催化剂，产率为78%，对映体过量值（ee）为81%。对具有不同结合模式的过渡结构进行的计算分析表明，最有利的过渡结构表现为方酰胺（NH）2与烯醇负离子亲核试剂的一个氧原子结合，而硝基烯烃则通过氢键与催化剂奎宁环单元的铵官能团配位。因此，方酰胺（NH）2基序偏向单原子结合的倾斜方向性可能是反应选择性的决定性因素。根据产物主要（-）-（R）对映体的旋光性，通过计算确定其绝对构型。
