DEVELOPMENT OF ASYMMETRIC RADICAL REACTIONS AND APPLICATION TO THE SYNTHESIS OF BIO-ACTIVE COMPOUNDS

不对称自由基反应的发展及其在生物活性化合物合成中的应用

基本信息

批准号：
08672441
负责人：
NISHIDA Atsushi
金额：
$ 1.47万
依托单位：
CHIBA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

1. DIASTEREOSELECTIVE RADICAL CYCLIZATION1) New chiral auxiliaries, trans-2-(N-benzenesulfonyl-N-benzylamino)cyclohexanol and its derivatives were developed and used for diastereoselective radical cyclization. When trans-2-(N- benzenesulfonyl-N-benzylamino)cyclohexyl 7-iodo-2,6-heptadienoate was reacted with nBu_3SnH in the presence of Et_3B and bulky Lewis acid, such as MAD, a diastereo mixture of (2- cyclopentenyl)acetate was obtained in 92% yield. After standard hydrolysis, (2-cyclopentenyl)acetic acid was obtained (53% ee) and the chiral auxiliary was recovered. Optically active (2- cyclopentenyl)acetic acid is a starting material for many biologically active compounds, such as coriolin, hirsutic acid C, and alepraic acid (a member of cyclopentenyl fatty acids).Optically active (2-cyclohexenyl)acetic acid (38% ee) was also obtained using the same auxiliary.2) Diastereoselective addition of tri-n-butyltin radical to chiral alpha, beta-unsaturated esters, having 8- phenylmenthyl grou … More p as a chiral auxiliary, was achieved in the presence of Lewis acid. Thus obtained beta-stannylester was converted to a chiral cyclopropane derivative.3) Chiral hydroxythiols, which were prepared from (R)-(+)-pulegone, were converted to chiral acetals, When the chiral acetals were irradiated using UV lamp in the presence of benzophenone, carbon radicals were generated and cyclized to chiral cyclopentane derivatives. Although diastereoselectivity was low, the reaction is a new method for the synthesis of chiral 2-substituted cyclopentanones.2. ENANTIOSELECTIVE RADICAL CYCLIZATIONWhen cyclohexyl 8-iodonona-2,8-dienoate was reacted with nBu_3SnH and Et_3B in the presence of chiral aluminum reagent, chiral (2-methylenecyclohexyl)acetate was obtained in 46% ee, This is the first example of enantioselective radical cyclization.3. NEW RADICAL SKELETAL REARRANGEMENT VIA ALKOXY RADICALThe radical reaction of epoxydecalin thiocarbonylimidazolide afforded rearranged bicyclic cyclooctanes. The reaction proceeded via ten-membered ring carbon radicals, which was generated by beta-cleavage of alkoxy radicals. This reaction is useful for some terpene synthesis having a cyclooctane ring. Less

1. 非对映选择性自由基环化 1) 开发了新型手性助剂反式-2-(N-苯磺酰基-N-苯甲基氨基)环己醇及其衍生物，并用于反式-2-(N-苯磺酰基-N-苯甲基氨基)的非对映选择性自由基环化。环己基7-碘-2,6-庚二烯酸酯与nBu_3SnH在Et_3B和大路易斯酸（例如MAD）的存在下反应，在标准水解后以92%收率获得（2-环戊烯基）乙酸酯的非对映混合物。获得了(53% ee)乙酸并回收了光学活性助剂(2-)。环戊烯基）乙酸是许多生物活性化合物的起始原料，例如科里林、多毛酸 C 和阿莱普拉酸（环戊烯基脂肪酸的成员）。光学活性的 (2-环己烯基)乙酸 (38% ee) 也被用于生产2)三正丁基锡基团非对映选择性加成到手性α、β-不饱和酯上，具有8-苯基薄荷基团… More p作为手性助剂，在路易斯酸存在下得到，将所得的β-甲锡烷基酯转化为手性环丙烷衍生物。3)由(R)-(+)制备手性羟基硫醇。 -胡薄荷酮，转化为手性缩醛，当手性缩醛在二苯甲酮存在下使用紫外线灯照射时，碳自由基虽然非对映选择性较低，但该反应是合成手性2-取代环戊酮的新方法。2．8-碘代环己酯与2,8-二烯酸环己酯反应。手性铝存在下的 Et_3B手性(2-亚甲基环己基)乙酸酯在46% ee中得到，这是对映选择性自由基环化的第一个例子。 3.通过烷氧基自由基进行的新的自由基重排环氧萘烷硫代羰基咪唑烷的自由基反应提供了重排的双环环辛烷。 -元环碳自由基，其产生通过烷氧基的β-裂解，该反应可用于某些具有环辛烷环的萜烯合成。