ISM, UMR 5255, University of Bordeaux and CNRS, 351, Cours de la liberation, 33400 Talence Cedex (France).
Chemistry. 2014 Nov 3;20(45):14771-82. doi: 10.1002/chem.201403662. Epub 2014 Sep 15.
The base-catalyzed intramolecular hydroamination of 1-ethylaminocyclohexa-2,5-dienes is described. The transformation proceeds through isomerization of the cyclohexa-1,4-dienyl fragment into the corresponding conjugated 1,3-diene prior to the hydroamination step. Attaching a chiral glycinol ether auxiliary on the amino group allows the protonation to occur with complete diastereocontrol. The resulting lithium amide then adds onto the 1,3-dienyl moiety, affording the desired fused pyrrolidine ring along with the corresponding lithium allylic anion. Protonation of the latter then proceeds with high regiocontrol to favor the resulting allylic amines. In contrast, when the reaction was performed on primary amines, fused pyrrolidines bearing a homoallylic amino group were obtained. The stereochemical course of the process and determination of the reaction pathways were established based on calculations performed at the DFT level. Finally, application of the methodology to the enantioselective synthesis of (+)-epi-elwesine, a crinane alkaloid, is described.
描述了 1-乙氨基环己二烯的碱催化分子内环氢胺化反应。该转化通过环己-1,4-二烯片段异构化为相应的共轭 1,3-二烯，然后进行氢胺化步骤。在氨基上连接手性甘氨醇醚辅助基允许质子化反应以完全的非对映选择性发生。所得的锂酰胺随后加成到 1,3-二烯部分，得到所需的稠合吡咯烷环以及相应的锂烯丙基阴离子。然后对后者进行质子化，具有高区域选择性，有利于得到相应的烯丙基胺。相比之下，当反应在伯胺上进行时，得到了带有偕二烯基氨基的稠合吡咯烷。基于在 DFT 水平上进行的计算，确定了该过程的立体化学过程和反应途径。最后，描述了该方法学在手性选择性合成（+）-表艾维斯碱（epi-elwesine），一种海胆烷生物碱中的应用。
