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

1)合成了新型手性助剂trans-2-(N-benzenesulfonyl-N-benzylamino)cyclohexanol及其衍生物，并用于非对映选择性自由基环化反应。反式-2-(N-苯磺酰基-N-苄氨基)7-碘-2，6-庚二烯酸环己酯在Et_3B和大块Lewis酸(如MAD)存在下与NBU_3SnH反应，以92%的产率合成了(2-环戊烯基)乙酸酯的非对映混合物。标准水解后得到(2-环戊烯基)乙酸(ee=53%)，并回收了手性助剂。光学活性的(2-环戊烯基)乙酸是许多生物活性化合物的起始原料，如科里奥林、水飞蓟酸C和对映体酸(环戊烯脂肪酸的一种)。光学活性的(2-环己烯基)乙酸(38%ee)也是用相同的助剂得到的。2)三正丁基锡自由基非对映选择性地加成手性α，β-不饱和酯，具有8-苯基薄荷基…在Lewis酸存在下，得到了更多的p作为手性助剂。3)将(R)-(+)-普利酮得到的手性羟基硫醇转化为手性缩醛，在二苯甲酮存在下用紫外灯照射手性缩醛，生成碳自由基并环化为手性环戊烷衍生物。虽然非对映选择性较低，但该反应是一种合成手性2-取代环戊酮的新方法。8-碘-2，8-二烯酸环己酯与NbU_3SnH和Et_3B在手性铝试剂存在下反应，在46%ee中得到手性(2-亚甲基环己基)乙酸酯，这是第一例不对称自由基环化反应。通过烷氧基辐射的新的自由基骨架重排环氧十烷基硫代羰基咪唑的自由基反应得到重排的双环环辛烷。反应是通过烷氧基的β-裂解生成的十元环碳自由基进行的。该反应对某些具有环辛烷环的萜类化合物的合成是有用的。较少

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