Departmento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid (Spain).
Chemistry. 2013 Sep 23;19(39):13207-15. doi: 10.1002/chem.201204594. Epub 2013 Aug 14.
The cerium(IV) ammonium nitrate (CAN)-catalyzed sequential multicomponent reaction between tryptamine, α,β-unsaturated aldehydes, and β-dicarbonyl compounds affords highly substituted indolo[2,3-a]quinolizines in a single synthetic operation. Two rings are generated through the creation of two C-C and two C-N bonds by a domino process comprising initial β-enaminone formation, followed by individual Michael addition, 6-exo-trig cyclization, iminium formation, and Pictet-Spengler steps. Furthermore, the reaction is diastereoselective and affords exclusively compounds with a trans relationship between the H-2 and H-12b protons. The use of amines bearing a less nucleophilic side chain aromatic ring (5-bromotryptamine, 3,4-dimethoxyphenylethylamine) prevents the Pictet-Spengler final step and leads to N-indolylethyl or N-phenylethyl-1,4-dihydropyridines, which are cyclized to the corresponding indolo[2,3-a]quinolizines or benzo[a]quinolizines in the presence of HCl in methanol/water. Treatment of the fused quinolizine derivatives with sodium triacetoxyborohydride led to the corresponding indolo[2,3-a]quinolizidines or benzo[a]quinolizidines, possessing four stereogenic centers, as mixtures of two diastereomers.
硝酸铈铵（CAN）催化的色胺、α,β-不饱和醛和β-二羰基化合物的串联多组分反应在单一合成操作中提供了高度取代的吲哚并[2,3-a]喹啉。通过包含初始β-烯胺酮形成、随后的单独迈克尔加成、6-endo-trig 环化、亚胺形成和皮克特-斯彭格勒步骤的多米诺过程，生成了两个环，通过两个 C-C 和两个 C-N 键的形成。此外，该反应具有立体选择性，仅提供 H-2 和 H-12b 质子之间具有反式关系的化合物。使用具有较少亲核性侧链芳环的胺（5-溴色胺、3,4-二甲氧基苯乙胺）可以防止皮克特-斯彭格勒的最后一步，并导致 N-吲哚基乙基或 N-苯乙基-1,4-二氢吡啶，在甲醇/水中存在 HCl 时，它们环化成相应的吲哚并[2,3-a]喹啉或苯并[a]喹啉。将稠合的喹啉衍生物用三乙酰氧基硼氢化钠处理导致相应的吲哚并[2,3-a]喹啉啶或苯并[a]喹啉啶，作为两种非对映异构体混合物，具有四个立体中心。
