Padwa Albert, Brodney Michael A, Lynch Stephen M, Rashatasakhon Paitoon, Wang Qiu, Zhang Hongjun
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
J Org Chem. 2004 May 28;69(11):3735-45. doi: 10.1021/jo049808i.
The intramolecular Diels-Alder reaction between an amidofuran moiety tethered onto an indole component was examined as a strategy for the synthesis of Aspidosperma alkaloids. Furanyl carbamate 23 was acylated using the mixed anhydride 26 to provide amidofuran 22 in 68% yield. Further N-acylation of this indole furnished 27 in 88% yield. Cyclization precursors were prepared by removing the carbamate moiety followed by N-alkylation with the appropriate alkyl halides. Large substituent groups on the amido nitrogen atom causes the reactive s-trans conformation of the amidofuran to be more highly populated, thereby facilitating the Diels-Alder cycloaddition. The reaction requires the presence of an electron-withdrawing substituent on the indole nitrogen in order for the cycloaddition to proceed. Treatment of N-allyl-bromoenamide 48 with n-Bu(3)SnH/AIBN preferentially led to the 6-endo trig cyclization product 50, with the best yield (91%) being obtained under high dilution conditions. The initially generated cyclohexenyl radical derived from 48 produces the pentacyclic heterocycle 50 by either a direct 6-endo trig cyclization or, alternatively, by a vinyl radical rearrangement pathway.
研究了连接在吲哚组分上的氨基呋喃部分之间的分子内狄尔斯-阿尔德反应，以此作为合成阿朴菲生物碱的一种策略。使用混合酸酐26对呋喃基氨基甲酸酯23进行酰化反应，以68%的产率得到氨基呋喃22。对该吲哚进一步进行N-酰化反应，以88%的产率得到27。通过去除氨基甲酸酯部分，然后用适当的卤代烃进行N-烷基化反应来制备环化前体。酰胺氮原子上的大取代基会使氨基呋喃的反应性s-反式构象占比更高，从而促进狄尔斯-阿尔德环加成反应。为了使环加成反应能够进行，该反应需要在吲哚氮上存在一个吸电子取代基。用正丁基(3)锡氢/偶氮二异丁腈处理N-烯丙基-溴代烯酰胺48，优先得到6-内型三氟环化产物50，在高稀释条件下可获得最佳产率（91%）。最初由48产生的环己烯基自由基通过直接的6-内型三氟环化反应或通过乙烯基自由基重排途径生成五环杂环50。
