Efficient Direct Synthesis of Aziridine‐Containing Chiral Tridentate Ligands by the Iminium‐Mediated Self‐Ring Opening Reaction of Enantiopure Aziridines and Salicylaldehydes

Abstract

An efficient method for the direct synthesis of aziridine-containing chiral tridentate ligands was developed from enantiopure aziridines and salicylaldehydes. The method achieved the regiospecific cleavage of more substituted CÀ N bonds of aziridines through an iminium-mediated self-ring opening reaction of aziridines with up to 95% yield and complete inversion of configuration. The (S)-2-alkylaziridine-derived tridentate ligands displayed excellent activity and stereoselectivity in the zinc trifluoromethanesulfonatecatalyzed asymmetric aldol reactions of acetone and aromatic aldehydes.

Catalyst‐Free Electrophilic Ring Expansion of N‐Unprotected Aziridines with α‐Oxoketenes to Efficient Access 2‐Alkylidene‐1,3‐Oxazolidines

“…Preparations and analytical data of 2‐diazo‐1,3‐diketones 1 [6d,11] and aziridines 2 , [15,22] and hydrolysis of product 3 aa * are provided in SI.…”

“…The AgOTf and Cu(OAc) 2 synergetically catalyzed reaction of activated N ‐tosylaziridines and 2‐diazo‐1,3‐dicarbonyls generated 2 H ‐1,4‐oxazines (Scheme 1c) [14] . Recently, we realized the electrophilic ring opening of nonactivated aziridines for the direct and efficient synthesis of chiral tridentate ligands under neutral conditions [15] . Herein, we present an unprecedented synthesis of 2‐(2‐oxoalkylidene)‐1,3‐oxazolidine derivatives via the catalyst‐free reaction of nonactivated N ‐unprotected aziridines and 2‐diazo‐1,3‐diketones under microwave‐assisted neutral conditions.…”

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

“…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.…”

“…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. However, our first report concerning such chiral derivatives appeared in 2017 [23].…”

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

“…( 5) direct synthesis from alkenes and amides or nitriles in the presence of electrophilic reagents [18,19]. Aziridines can be considered as the NCC structural fragment after ring-opening and have been applied in the synthesis of aziridine-imine-containing chiral tridentate ligands [20], 2-alkylideneoxazolidines [21] and N-vinylamides [22]. We envisioned that the reaction of ethoxycarbonylketenes and aziridines can be applied for the synthesis of ethyl 2-(oxazolin-2-yl)alkanoates.…”