Arai Kenzo, Lucarini Simone, Salter Matthew M, Ohta Kentaro, Yamashita Yasuhiro, Kobayashi Shu
Graduate School of Pharmaceutical Sciences, The University of Tokyo, The HFRE Division, ERATO, Tokyo, Japan.
J Am Chem Soc. 2007 Jul 4;129(26):8103-11. doi: 10.1021/ja0708666. Epub 2007 Jun 13.
The discovery and development of a new Lewis acid system based on a complex formed from niobium(V) methoxide and (R)-3,3'-bis(2-hydroxy-3-isopropylbenzyl)-1,1'-binaphthalene-2,2'-diol, a novel tetradentate BINOL derivative, is presented. The system was shown to be extremely effective in promoting the desymmetrative ring opening of linear and cyclic meso-epoxides using anilines as nucelophiles, delivering the corresponding (R,R) anti-amino alcohols in good to excellent yields (up to quantitative) and excellent enantioselectivity (up to 96% ee). Furthermore, the catalyst system displays a remarkable sensitivity to steric bulk at the beta-carbon of the epoxide, selectively facilitating ring opening of smaller epoxides in the presence of more sterically hindered epoxides. This property was confirmed by a series of competition reactions using a mixture of meso-2-butene oxide and another aliphatic meso-epoxide, with the result that the former, less encumbered epoxide reacted preferentially with up to 98% chemical selectivity. While it was found to be most convenient to conduct the reactions with 10 mol % catalyst loading at 0.16 M, at higher overall concentration the reaction still proceeded efficiently with as little as 0.25 mol % catalyst to give the desired products with no significant reduction in yields or enantioselectivities. In addition, the current catalyst system was also found to mediate the asymmetric ring opening of nonsymmetrical cis-2-alkene oxides with anilines to give preferentially the corresponding (2R,3R)-2-amino-3-ols arising from ring opening at the methyl terminus, in excellent yields (up to quantitative) and good to excellent regio- and enantioselectivities (up to 18:1 and >99% ee, respectively). Intriguingly, it was discovered that the same catalyst system also promoted the ring-opening desymmetrization of aziridines with aniline nucleophiles to give the corresponding (S,S) vicinal diamines in good to excellent yields and enantioselectivity (up to 95% and 84% ee [>99% ee following a single recrystallization]). Catalyst systems that promote closely related reactions with opposite stereochemical outcomes in high selectivity such as the current niobium system are extremely unusual. To the best of our knowledge, this report constitutes not only the first example of the catalytic desymmetrization of both meso-epoxides and meso-aziridines but also a rare example of such complementary stereoselectivity in a catalytic reaction.
本文介绍了一种新型路易斯酸体系的发现与开发，该体系基于由五价铌甲氧基化物与一种新型四齿联萘酚衍生物（R）-3,3'-双（2-羟基-3-异丙基苄基）-1,1'-联萘-2,2'-二醇形成的配合物。该体系在以苯胺为亲核试剂促进线性和环状内消旋环氧化物的去对称开环反应中表现出极高的效率，能以良好至优异的产率（高达定量）和出色的对映选择性（高达96% ee）得到相应的（R,R）反式氨基醇。此外，该催化剂体系对环氧化物β-碳上的空间位阻表现出显著的敏感性，在存在空间位阻更大的环氧化物时，能选择性地促进较小环氧化物的开环反应。这一性质通过一系列使用内消旋-2-丁烯氧化物和另一种脂肪族内消旋环氧化物混合物的竞争反应得到证实，结果是前者，即空间位阻较小的环氧化物优先反应，化学选择性高达98%。虽然发现以0.16 M的浓度使用10 mol%的催化剂负载量进行反应最为方便，但在更高的总浓度下，反应仍能以低至0.25 mol%的催化剂高效进行，得到所需产物，产率和对映选择性均无显著降低。此外，还发现当前的催化剂体系也能介导不对称顺式-2-烯烃氧化物与苯胺的不对称开环反应，优先得到相应的（2R,3R）-2-氨基-3-醇，该产物由甲基端开环产生，产率优异（高达定量），区域选择性和对映选择性良好至优异（分别高达18:1和>99% ee）。有趣的是，发现相同的催化剂体系还能促进氮丙啶与苯胺亲核试剂的开环去对称化反应，以良好至优异的产率和对映选择性（高达95%和84% ee [单次重结晶后>99% ee]）得到相应的（S,S）邻二胺。像当前的铌体系这样能在高选择性下促进具有相反立体化学结果的密切相关反应的催化剂体系极为罕见。据我们所知，本报告不仅构成了内消旋环氧化物和内消旋氮丙啶催化去对称化的首个实例，也是催化反应中这种互补立体选择性的罕见实例。
