Mechanistic Studies and Synthetic Applications of 5-Endo Radical Cyclization

研究了n-乙烯基α -halo酰胺5-末端自由基环化的机理及其在生物活性生物碱合成中的应用，得到的结果如下：1、n-苯基-2,2,2-三氯- n-[2-（苯基硫）环己基-1-烯-1-基]乙酰胺在沸腾甲苯中自由基环化得到5-e。正三角环积，而在室温下，它得到4外三角环积。结果可以用4-外环化的可逆性来解释。短句来源从取代基对自由基中心和氮原子的影响以及反应温度的角度考察了bu_3snh介导的2-halo- n -（3,4-二氢-2-萘基）乙酰胺环化反应的区域选择性（4-外三角对5-内三角）。当自由基中心的取代基是氢或氯原子时，沸化甲苯的4-外三角环化（β -内酰胺形成）更有利，而烷基、苯基和苯基硫基等自由基稳定取代基则主要或完全导致5-内三角环化（γ -内酰胺形成）。而在沸腾的苯中，甲基取代基主要生成β -内酰胺，而在氮原子上甲基取代基和苄基取代基之间的产物分布没有显著差异。这些结果将从动力学或热力学的角度加以讨论。3、2-碘- n- [(S)-1-苯乙基]- n-（6-氧环己基-1-烯-1-基）乙酰胺的自由基环化反应以5-内三角方式进行，具有适度的非对映选择性，得到(3aS,7aR)-八氢吲哚-2,7-二酮为主要产物，转化为(-)- γ -石蜡烷。4、N-（环己基-1-烯-1-基）-N-（对甲氧基苯基）- 2-（3,4 -亚甲二氧苯基）- 2-（苯硫基）乙酰胺自由基环化得到(3R*, 3aS*, 7aS*) -3-芳基氢吲哚-2- 1，并转化为合成(*)-胰腺碱的关键中间体。少

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