STEREOSELECTIVE SYNTHESIS OF TRANS-2-(INDOL-3-YL)CYCLOPROPYLAMINES - RIGID TRYPTAMINE ANALOGS

A procedure for the preparation of trans-2-(indol-3-yl)cyclopropylamines is reported. The key step in the sequence is a stereoselective palladium-catalyzed cyclopropanation of the indole-3-acryloyl derivative of Oppolzer's chiral sultam (bornane[10,2]sultam) with diazomethane, following by the purification of the resulting diastereomeric cyclopropanated sultams by recrystallization. Base hydrolysis of the pure crystalline diastereomers gave the resolved indolylcyclopropane carboxylic acids. These could be converted into enantiomers of indolylcyclopropylamine by Curtius rearrangement, which did not affect the absolute configuration. In addition, single crystal X-ray erystallography of the cyclopropanated sultam was used to determine the absolute configuration of the intermediate indolylcyclopropanecarboxylic acid and thus to establish the configuration of the final compound.