Gensini Martina, de Meijere Armin
Institut für Organische Chemie, der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Goettingen, Germany.
Chemistry. 2004 Feb 6;10(3):785-90. doi: 10.1002/chem.200305068.
Starting from pyrrole- and indole-2-carboxylic acids 5 a and 5 b, the tri- and tetracyclic N,N-dibenzylcyclopropylamines 7 a and 7 b have been synthesized in 52 and 33 % overall yield, respectively. The synthesis of the enantiopure tetracyclic diamine 10 has been achieved applying the established set of reactions to N-tert-butoxycarbonylindoline-2-carboxylic acid (8) in 46 % overall yield. The amide 15 could not be prepared in the same way starting from the N-tert-butoxycarbonylproline 11. In fact, in the allylation step the stereogenic center was deprotonated and the doubly alkylated amide 13 was formed. However, the desired intermediate 15 could be obtained from L-proline in 49 % yield performing first the N-allylation step, then the introduction of the amide function. From 15, the cyclopropane-annelated pyrrolizidine 16 was obtained in 70 % yield as a mixture of (1aS,6aS,6bR)-16 and (1aR,6aS,6bS)-16 diastereoisomers in a ratio of 1:2.9.
从吡咯 -2 - 羧酸（5a）和吲哚 -2 - 羧酸（5b）出发，分别以52%和33%的总收率合成了三环和四环的N,N - 二苄基环丙胺（7a）和（7b）。通过将一系列既定反应应用于N - 叔丁氧羰基吲哚啉 -2 - 羧酸（8），以46%的总收率实现了对映体纯的四环二胺（10）的合成。从N - 叔丁氧羰基脯氨酸（11）出发，无法以同样的方式制备酰胺（15）。实际上，在烯丙基化步骤中，手性中心发生去质子化，形成了双烷基化酰胺（13）。然而，通过先进行N - 烯丙基化步骤然后引入酰胺官能团，从L - 脯氨酸可以以49%的收率获得所需的中间体（15）。从（15）出发，以7:2.9的比例得到环丙烷稠合的吡咯里西啶（16），收率为70%，它是（1aS,6aS,6bR）-16和（1aR,6aS,6bS）-16非对映异构体的混合物。
