Mechanistic Studies and Synthetic Applications of 5-Endo Radical Cyclization

5-Endo自由基环化的机理研究及合成应用

基本信息

批准号：
09672176
负责人：
IKEDA Masazumi
金额：
$ 1.79万
依托单位：
Kyoto Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Mechanistic aspects in the 5-endo radical cyclization of N-vinylic alpha-halo amides and its application to the synthesis of biologically active alkaloids were investigated, The results obtained were as follows :1, The radical cyclization of N-benzyl-2,2,2-trichloro-N-[2-(phenylthio) cyclohex-1-en-1-yl] acetamide in boiling toluene gave the 5-e.ndo-trig cyclization product, whereas, at room temperature, it gave the 4-exo-trig cyclization product. The results may be explained in terms of the reversibility of the 4-exo cyclization.2, The regioselectivity in Bu_3SnH-mediated radical cyclizations (4-exo-trig vs 5-endo-trig) of a range of 2-halo-N-(3,4-dihydro-2-naphthyl)acetamides has been examined from the standpoint of the effects of substituents on the radical center and on the nitrogenatom as well as the reaction temperature. When the substituent on the radical center is a hydrogen or chlorine atom, the 4-exo-trig cyclization (the beta-lactam formation) is favored in boiling toluene, w … More hile the radical stabilizing substituents such as alkyl, phenyl, and phenylthio groups bring about the 5-endo-trig cyclization (the gamma-lactam formation) predominantly or exclusiyely. In boiling benzene, however, the predominant formation of the beta-lactams is observed for the methyl substituent, On the other hand, no remarkable difference in the product distributions between the methyl and benzyl substituents on the nitrogen atom is observed. These results are discussed in terms of kinetic or thermodynamic considerations.3, The radical cyclization of 2-iodo-N-[(S)-1-phenylethyl]-N-(6-oxocyclohex-1-en-1-yl)acetamide proceeded in a 5-endo-trig manner with moderate diastereoselectivity to give the (3aS,7aR)-octahydroindole-2,7-dione as the major product, which was converted into (-)-gamma-lycorane.4, The radical cyclization of N-(cyclohex-1-en-1-yl)-N-(p-methoxybenzyl) -2- (3, 4-methylenedioxyphenyl) -2- (phenylthio) acetamide gave (3R*, 3aS*, 7aS*) -3-aryloctahydroindol-2-one, which was transformed into the key intermediate for the synthesis of (*)-pancracine. Less

Mechanistic aspects in the 5-endo radical cyclization of N-vinylic alpha-halo amides and its application to the synthesis of biologically active alkaloids were investigated, The results obtained were as follows:1, The radical cyclization of N-benzyl-2,2,2-trichloro-N-[2-(phenylthio) cyclohex-1-en-1-yl] acetamide in boiling toluene gave 5-E.NDO-Trig环化产品，而在室温下，它给出了4-Exo-Trig环化产品。 The results may be explained in terms of the reversibility of the 4-exo cyclization.2, The regulatoryselectivity in Bu_3SnH-mediated radical cyclizations (4-exo-trig vs 5-endo-trig) of a range of 2-halo-N-(3,4-dihydro-2-naphthyl)acetamides has been examined from the standpoint of the effects of subtituents on the radical center and在氮气以及反应温度上。当激进中心的亚物质是氢或氯原子时，4- exo-Trig环化（β-内酰胺）形成（β-内酰胺形成）以沸腾的甲苯为有利于…更受激根稳定的亚titus，例如烷基，苯基和苯基苯基和苯基基团（如5-苯甲酸甲基苯基和苯基苯基苯基）的形式（排他性。然而，在沸腾的苯中，观察到甲基亚tit剂量的β-内酰胺的主要形成，另一方面，观察到甲基和苄基替代剂之间的产物分布在氮原子上的产物分布没有显着差异。根据动力学或热力学考虑来讨论这些结果。3，2- iodo-n- [（S）-1-苯基乙基乙基] -N-（6-氧氧氧化苯基乙基苯基乙基乙基苯基乙基苯基乙基）（6-氧氧氧化物1- eN-1--en-1-基）乙酰氨酰胺以5-末端的方式进行，以中等的iaterecoselectivity diacerecoselectivity进行。（3AS，7AR）-Conthydroindole-2,7-二酮作为主要产品，将其转换为（ - ） - γ-柠檬烷。（3r*，3AS*，7AS*）-3-芳二氢醇-2-ONE，它被转化为合成（*） - pancracine合成的关键中间体。较少的