Practical Synthesis of Phisiologically Active Substances Using Functionalized Lewis Acids

成功利用功能化路易斯酸三（2,6-二苯基苯氧化铝）（ATPH），观察到分子内自由基环化过程中存在显著的模板效应。例如，3-碘丙基- 3-苯基丙基醚在ATPH的影响下，在Bu_3SnH和Et_3B的催化量下，在78 C的甲苯中进行1 h的分子内自由基环化反应，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，得到一个简单的还原产物作为主要产物，并伴随少量的环化产物形成。值得注意的是，在ATPH存在或不存在的情况下，环化产物的E/Z选择性完全相反。ATPH产生这种高效模板效应的原因是在铝配位中心前形成了良好的反应环境。这是第一个用设计Lewis酸来控制自由基反应途径的例子。使用ATPH作为功能化Lewis酸，我们还开发了一种概念性的新两亲性共轭烷基化物，用于有效阻断醛羰基，从而允许迄今为止难以将反应性亲核试剂共轭添加到α， β -不饱和醛上。在各种功能化ATPH衍生物中，作为具有特定反应环境的设计刘易斯酸，三铝[2,6-二（对氟苯基）苯氧化合物]（p-F-ATPH）和三铝[2,6-二（3,4,5-三氟苯基）苯氧化合物]（3,4,5- f_3 -ATPH）对该转化非常有效。这种仿生体系的突出之处是首次成功地通过与功能化Lewis酸p-F-ATPH络合，将烯丙基锂试剂偶联到α， β -不饱和醛上，得到了具有优异选择性的所需共轭加合物。除此之外，基于双齿有机铝和钛路易斯酸对羰基的选择性双亲电活化，羰基化合物在缩醛上实现了化学选择性功能化。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