Cyclopropane-annelated azaoligoheterocycles by Ti-mediated intramolecular reductive cyclopropanation of cyclic amino Acid amides.
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.
Gensini
Martina
M
Institut für Organische Chemie, der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Goettingen, Germany.
de Meijere
Armin
A
D000577:Amides / Q000138:chemical synthesis*; D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D003521:Cyclopropanes / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D007212:Indolizines / Q000138:chemical synthesis; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis; D014025:Titanium / Q000737:chemistry*
D000577:Amides; D000596:Amino Acids; D003521:Cyclopropanes; D006571:Heterocyclic Compounds; D007212:Indolizines; D011759:Pyrrolidines; D014025:Titanium