Practical Synthesis of Phisiologically Active Substances Using Functionalized Lewis Acids

利用功能化的刘易斯酸--三（2，6-二苯基苯酚）铝（ATPH），在分子内环化自由基过程中观察到了显著的模板效应。例如，3-碘丙基-3-苯基丙炔基醚在ATPH作用下与Bu_3SnH和催化量的Et_3B在甲苯中于-78 ℃下发生分子内环化反应，得到环醚作为唯一的可分离产物，而在没有ATPH的情况下，在其他类似的反应条件下，得到简单的还原产物作为主要产物，伴随着少量环化产物的形成。ATPH的存在和不存在对环化产物的E/Z选择性的影响是完全相反的，这种有效的模板效应的来源是由于在铝配位中心前创造了明确的反应环境。这代表了第一个用设计师刘易斯酸控制自由基反应途径的例子 关于我们 使用ATPH作为官能化的刘易斯酸，我们还开发了一种概念上新的两亲性共轭烷基化，用于有效地阻断醛羰基，从而允许迄今为止困难的反应性亲核试剂与α，β-不饱和醛的共轭加成。在各种功能化的ATPH衍生物中，三[2，6-二（对氟苯基）苯酚]铝（p-F-ATPH）和三[2，6-二（3，4，5-三氟苯基）苯酚]铝（3，4，5-F_3-ATPH）作为具有特定反应环境的设计刘易斯酸被发现是这种转化的高效催化剂。该仿生体系的突出表现是首次成功地将烯丙基锂试剂通过与官能化的刘易斯酸p-F-ATPH络合而与α，β-不饱和醛进行共轭加成，以优异的选择性得到所需的共轭加合物。双齿有机铝和钛刘易斯酸基于双亲电性，实现了羰基化合物对缩醛的化学选择性官能化选择性地活化羰基。少

A remarkable template effect in the intramolecular radical cyclization process has been observed by the successful utilization of functinalized Lewis acid, aluminum tris (2,6-diphenylphenoxide) (ATPH). For example, intramolecular radical cyclization of 3-iodopropyl 3-phenylpropynyl ether under the influence of ATPH with Bu_3SnH and catalytic amount of Et_3B in toluene at-78ﾟC for 1 h affords cyclic ether as a sole isolable product, while without ATPH under otherwise similar reaction conditions a simple reduction product is obtained as a major product with concomitant minor formation of the cyclization product. Notably, the E/Z selectivity in the cyclization products is totally opposite in the presence or absence of ATPH.The origin of this efficient template effect by ATPH would be ascribed to the well-defined reaction environment created in front of aluminum coordination center. This represents the first example of controlling radical reaction pathway with a designer Lewis acid in view … More of the molecular recognition approach.Using ATPH as a functionalized Lewis acid, we have also developed a conceptually new amphiphilic conjugate alkylation for effective blocking of aldehyde carbonyls, thereby allowing the hitherto difficult conjugate addition of reactive nucleophiles to alpha, beta-unsaturated aldehydes. Among various functionalized ATPH derivatives as a designer Lewis acid possessing the specific reaction environment, aluminum tris [2,6-bis (p-fluorophenyl) phenoxide] (p-F-ATPH) and aluminum tris [2,6-bis (3,4,5-trifluorophenyl) phenoxide] (3,4,5-F_3-ATPH) were found to be highly effective for this transformation. This biomimetic system is highlighted by the first successful conjugate addition of allyllithium reagents to alpha, beta-unsaturated aldehydes by complexation with the functionalized Lewis acid, p-F-ATPH,giving the desired conjugate adducts with excellent selectivity.In addition to these researches, chemoselective functionalization of carbonyl compounds over acetals has been achieved by bidentate organoaluminum and titanium Lewis acids based on the double electrophilic activation of carbonyls selectively. Less