Practical Synthesis of Phisiologically Active Substances Using Functionalized Lewis Acids

使用功能化路易斯酸实际合成生理活性物质

基本信息

批准号：
08555225
负责人：
MARUOKA Keiji
金额：
$ 9.86万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

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

通过成功利用功能化路易斯酸三(2,6-二苯酚铝)(ATPH)，观察到分子内自由基环化过程中显着的模板效应，例如3-碘丙基3-苯基丙炔基醚在分子内自由基环化。甲苯中Bu_3SnH和Et_3B催化量对ATPH的影响在-78°C 下反应 1 小时，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，则获得简单的还原产物作为主要产物，同时形成少量环化产物，值得注意的是 E/Z。在存在或不存在 ATPH 的情况下，环化产物的选择性完全相反。ATPH 的这种有效模板效应的起源可归因于在铝配位中心之前创建的明确的反应环境。代表了第一个利用设计者路易斯酸控制自由基反应途径的例子，考虑到分子识别方法。使用ATPH作为功能化路易斯酸，我们还开发了一种概念上新的两亲性共轭烷基化，可有效阻断醛羰基，从而在各种功能化的 ATPH 衍生物中，铝作为具有特定反应环境的设计者路易斯酸，允许反应性亲核试剂与 α，β-不饱和醛进行迄今为止困难的共轭加成。三[2,6-双（对氟苯基）苯酚]（p-F-ATPH）和三[2,6-双（3,4,5-三氟苯基）苯酚]铝（3,4,5-F_3-ATPH）发现对于这种转化非常有效，该仿生系统通过首次成功地将烯丙基锂试剂共轭添加到α，β-不饱和醛中而得到强调。与官能化路易斯酸，p-F-ATPH 络合，得到具有优异选择性的所需共轭加合物。除了这些研究之外，基于双齿亲电子活化的双齿有机铝和钛路易斯酸也实现了羰基化合物相对于缩醛的化学选择性官能化选择性地减少羰基。