Bélanger Guillaume, April Myriam, Dauphin Etienne, Roy Stéphanie
Laboratoire de synthèse organique et de développement de stratégies de synthèse, Département de Chimie, Université de Sherbrooke, 2500 boulevard Université, Sherbrooke, Québec, J1K 2R1, Canada.
J Org Chem. 2007 Feb 16;72(4):1104-11. doi: 10.1021/jo061556t.
A sequence of chemoselective activation of N-acylaminoacids, münchnone generation, intramolecular 1,3-dipolar cycloaddition, and ring opening efficiently generated functionalized polycyclic structures such as cyclopenta[b]pyrroles or zwitterionic bicyclo[4.3.0]nonane or bicyclo[3.3.0]octanes in one operation is given. These zwitterionic species were isolated for the first time and were subsequently reduced to bicyclic aminoalcohols. The effect of the substitution of both the dipolarophile and the münchnone on the intramolecular cycloaddition outcome was examined. It was found that either nonactivated or electron-poor alkenes can react with the münchnone if these alkenes are tethered at position 4 on the münchnone (2, R2 = alkene tether), whereas only an electron-poor alkene at position 2 (2, R3 = alkene tether) could undergo successful cycloaddition. Also, münchnones substituted at position 2 with a phenyl (2, R3 = Ph) showed a dramatic increase in reactivity, whereas a phenyl at position 4 (2, R2 = Ph) had a very limited effect.
给出了一种通过对N-酰基氨基酸进行化学选择性活化、生成米氏酮、分子内1,3-偶极环加成和开环反应，在一步操作中高效生成功能化多环结构（如环戊并[b]吡咯或两性离子双环[4.3.0]壬烷或双环[3.3.0]辛烷）的序列。这些两性离子物种首次被分离出来，随后被还原为双环氨基醇。研究了亲偶极体和米氏酮的取代对分子内环加成结果的影响。结果发现，如果这些烯烃连接在米氏酮的4位（2，R2 = 烯烃连接基），则未活化的或缺电子的烯烃都能与米氏酮反应，而只有2位的缺电子烯烃（2，R3 = 烯烃连接基）能成功进行环加成。此外，2位被苯基取代的米氏酮（2，R3 = Ph）显示出反应活性的显著增加，而4位的苯基（2，R2 = Ph）的影响非常有限。
