Alkylation of indoles by aziridinium ions: New rapid access to tetrahydro-β-carbolines (THBCs)

Article abstract of DOI:10.1016/j.tet.2014.05.009

The alkylation of indoles by aziridinium ions generated in situ from β-amino chlorides was explored. The outcome of this reaction strongly relied on the substitution pattern of the starting β-amino chloride and requires silver tetrafluoroborate activation to proceed in reasonable yield. Ephedrine- and pseudoephedrine-derived N-cyanomethyl-β-amino chlorides afforded the corresponding tryptamines in a regio- and stereoselective manner and subsequent silver(I)-promoted Pictet-Spengler reactions produced 4-phenyl substituted THBCs in good yields. Unexpected epimerization at C-3 was found in these reactions, producing trans-3,4-disubstituted THBCs stereoselectively.