Establishment of Highly Selective Radical Cyclization and Application to the Synthesis of Biologically Active Compounds

研究了bu_3snh介导的区域选择性和立体选择性自由基环化。结果总结如下：1。n -乙烯基α -halo酰胺的4-外显基环化，在氮原子或羰基的α位置上带有手性助剂，被发现具有高度的非对映选择性，得到光学活性的β -内酰胺。应用该方法合成了(+)-PS-5、(+)-噻霉素和1 - β -甲基碳青霉烯2等光活性碳青霉烯类抗生素。氮原子上有手性助剂的N-（1-环己烯-1-酰基）- α -卤代乙酰胺的5端自由基环化具有中等程度的非对映选择性，从而得到光学活性的八羟基吲哚-2- 1。该方法应用于(-)- γ -石蜡烷的全合成。研究了N-（2-苯基硫代-1-环己烯-1-基）- α -卤乙胺的自由基环化过程，发现反应温度对环化过程有明显的影响。因此，在室温下，4-外环化占主导地位，而在较高温度下（在沸腾的甲苯中），5-内环化占主导地位。n -乙烯基-2-溴苯甲酰胺或n -乙烯基-2-（2-溴苯基）乙酰酰胺的n -乙烯基键末端含有一个苯基硫基团，它们分别以5-外三角或6-外三角方式进行自由基环化，有效地生成异吲哚酮和异喹啉酮。并将该方法应用于辣椒碱、lennoxamine、tetrahydropalmatine、salatine等生物碱的合成。N- [o-（2-丙烯基）苯基]-2,2-二（苯基硫代）乙酰胺以8-内三角方式发生自由基环化，得到苯并氮唑酮衍生物。

Bu_3SnH-mediated regio- and stereoselective radical cyclizations of alpha-holo amides have been examined. The results are summarized below.1. The 4-exo radical cyclization of N-vinylic alpha-halo amides, bearing a chiral auxiliary on the nitrogen atom or at the alpha-position of the carbonyl group, was found to proceed with high degree of diastereoselectivy to give optically active beta-lactams. The methods were applied to the synthesis of optically active carbapenem antibiotics such as (+) -PS-5, (+) -thienamycin and 1beta-methylcarbapenem.2. The 5-endo radical cyclization of N- (1-cyclohexenen-1-yl) -alpha-haloacetamides bearing a chiral auxiliary on the nitrogen atom was found to proceed with moderate degree of diastereoselectivy t give optically active octahydroindol-2-ones. The method was applied to the total synthesis of (-) -gamma-lycorane.3. The radical cyclization of N- (2-phenylthio-1-cyclohexenen-1-yl) -alpha-haloacetamies has been examined, and it was found that the course of the cyclizations was atrikingly affected by the reaction temperature employed. Thus, at room temperature, 4-exo cyclization predominated, and at higher temperature (in boiling toluene), 5-endo cyclization predominated.4. The kN-vinyl-2-bromobenzamides or N-vinyl-2- (2-bromophenyl) acetamides bearing a phenylthio group at the terminus of their N-vinylic bond were found to undergo radical cyclization in a 5-exo-trig or in a 6-exo-trig manner effectively to give isoindolone and isoquinolinones, respectively. The methods were applied to the synthesis of some alkaloids such as chilenine, lennoxamine, tetrahydropalmatine and saulatine.5. The N- [o- (2-propenyl) phenyl] -2,2-bis (phenylthio) acetamides were found to undergo radical cyclization in an 8-endo-trig manner to give benzoazocinone derivatives.