Practical Synthesis of Phisiologically Active Substances Using Functionalized Lewis Acids

功能化Lewis酸三(2，6-二苯基苯氧铝)(ATPH)在分子内自由基环化反应中具有显著的模板效应。例如，3-碘丙基-3-苯丙基醚在ATPh的影响下与Bu_3SnH和Et_3B在甲苯中于-78ﾟC反应1h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，而在其他类似的反应条件下，没有ATPH，环化产物以简单的还原产物为主，伴随有少量的环化产物。值得注意的是，在有或没有ATPH的情况下，环化产物中的E/Z选择性完全相反。ATPH的这种有效的模板效应的起源可以归因于在铝配位中心前面创建的明确的反应环境。这是在VIEW…中用设计者刘易斯酸控制自由基反应途径的第一个例子更多的分子识别方法。使用ATPH作为功能化的Lewis酸，我们还开发了一种概念上新的两亲共轭烷基化反应，用于有效封闭醛羰基，从而允许反应性亲核剂与α，β-不饱和醛进行迄今困难的共轭加成。在各种具有特定反应环境的功能化ATPH衍生物中，三[2，6-二(对氟苯基)苯氧铝](p-F-ATPH)和三[2，6-二(3，4，5-三氟苯基)苯氧铝](3，4，5-F3-ATPH)对该反应具有较高的催化活性。这一仿生体系的突出特点是首次成功地将烯丙基锂试剂与功能化的Lewis酸p-F-ATPH络合到α，β-不饱和醛上，得到了选择性很好的共轭加合物。此外，基于羰基的双重亲电活化，双齿有机铝和钛的Lewis酸选择性地实现了羰基化合物对缩醛的化学选择性官能化。较少

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