Synthesis of chiral 1-(2-aminoalkyl)aziridines via the self-opening reaction of aziridine

Abstract

A novel approach to the synthesis of optically pure 1-(2-aminoalkyl)aziridines via a nucleophilic ring-opening reaction of aziridine is presented. The reaction takes place under mild conditions in the presence of ZnBr 2 with moderate chemical yields. The formation of 1-(2-aminoalkyl)aziridines, starting from optically pure NHaziridines, occurs selectively, leading to a single diastereoisomer.

Enantiodivergent Aldol Condensation in the Presence of Aziridine/Acid/Water Systems

“…Chiral catalysts 1-10 (Figure 2) were synthesized using a two-step synthesis from chiral, optically pure NH-aziridines [22] according to a procedure described earlier [23,24]. Two equivalents of enantiomerically pure chiral aziridines reacted with one equivalent of ZnBr 2 at 80 • C without solvent.…”

“…The configuration of all the aldol products was established according to optical rotation signs, retention times in HPLC chromatograms, and by comparison with literature data [22][23][24][25][26][27][28]. All data are described in Appendix A and chromatograms are included in Supplementary Materials.…”

“…A solution of the corresponding 1-(2-aminoalkyl)aziridine [23] (1 mmol) and aromatic aldehyde (1 mmol) in MeOH (10 mL) was refluxed for 16 h. After this time, a solvent was evaporated and the product was purified using flash chromatography (silica gel, hexane/AcOEt in gradient) to afford the corresponding chiral imines 1-10 as colorless, viscous oils.…”

“…In 2019, Chen et al [25] prepared chiral aziridine imines and investigated its use in organocatalysis. However, our first report concerning such chiral derivatives appeared in 2017 [23]. As a continuation of the studies, we herein present the synthesis of aziridine ligands with specific configurations by starting from 1-(2-aminoalkyl)aziridines and any carbonyl compound (not only hydroxy-substituted), which is more useful from a synthetic point of view.…”

“…Based on our experience in the field of asymmetric synthesis using aziridine-containing ligands/organocatalysts [19][20][21][22] and achieving very promising preliminary results [23,24], we decided to synthesize a series of chiral, diastereomerically pure imines from 1-(2-aminoalkyl)aziridines and to investigate their catalytic activity in the enantiodivergent and/or diastereodivergent asymmetric aldol reaction in the presence of water. In 2019, Chen et al [25] prepared chiral aziridine imines and investigated its use in organocatalysis.…”