Functionalized tryptamines are targets of interest for development as small molecule therapeutics. The ring opening of aziridines with indoles is a powerful method for tryptamine synthesis where isomer formation can be controlled. 3,5-Dinitrobenzoyl (DNB)-protected aziridines undergo regioselective, enantiospecific ring opening to produce β-substituted tryptamines for a series of indoles. Attack at the more substituted aziridine carbon occurs in an SN2-like fashion to generate DNB-tryptamine products as synthetic precursors.

Aziridines are important synthetic intermediates for the generation of nitrogen-containing molecules. N-Acylaziridines undergo rearrangement by ring expansion to produce oxazolines, a process known as the Heine reaction. The first catalytic, enantioselective Heine reaction is reported for meso-N-acylaziridines where a palladium(II)–diphosphine complex is employed. The highly enantioenriched oxazoline products are valuable organic synthons and potential ligands for transition-metal catalysis.Keywords: aziridine; desymmetrization; enantioselective; heterocycles; palladium

Functionalized tryptamines are targets of interest for development as small molecule therapeutics. The ring opening of aziridines with indoles is a powerful method for tryptamine synthesis if site selectivity can be controlled. 4-Nitrobenzyl carbamate (PNZ)-protected aziridines undergo regioselective ring opening to produce β-substituted tryptamines for a series of indoles. The PNZ-protected tryptamines can be further manipulated by PNZ removal under mild conditions.

N-Acylaziridines are important starting materials for the synthesis of chiral amine derivatives. The traditional methods for producing these activated aziridines have significant drawbacks. The gram scale synthesis of N-acylaziridines by deprotection of N-tosylaziridines and reprotection with N-hydroxysuccinimide derivatives is described. Mono- and disubstituted aziridines perform well, with complete retention of stereochemical purity. The consistently moderate yields are linked to the N-tosylaziridine deprotection step, while acylation with N-hydroxysuccinimide derivatives is highly efficient.

Plasmodium falciparum, the deadliest malarial parasite species, has developed resistance against nearly all man-made antimalarial drugs within the past century. However, quinine (QN), the first antimalarial drug, remains efficacious worldwide. Some chloroquine resistant (CQR) P. falciparum strains or isolates show mild cross resistance to QN, but many do not. Further optimization of QN may provide a well-tolerated therapy with improved activity versus CQR malaria. Thus, using the Heck reaction, we have pursued a structure–activity relationship study, including vinyl group modifications of QN. Certain derivatives show good antiplasmodial activity in QN-resistant and QN-sensitive strains, with lower IC50 values relative to QN.

Aziridines are important synthetic intermediates which readily undergo ring-opening reactions. It is demonstrated that electron-rich phosphines are efficient catalysts for the regioselective rearrangement of N-acylaziridines to oxazolines. The reactions occur in excellent yield under neutral conditions. Evidence is provided for an addition/elimination mechanism by generation of a phosphonium intermediate. Similar intermediates may be useful for the development of alternate aziridine ring-opening processes and stereoselective synthesis with enantiopure phosphines.