Cyclopropane‐Annelated Azaoligoheterocycles by Ti‐Mediated Intramolecular Reductive Cyclopropanation of Cyclic Amino Acid Amides

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Abstract
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.