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

Abstract

2‐(2‐Oxoalkylidene)‐1,3‐oxazolidine derivatives were synthesized in good to excellent yields regiospecifically through the catalyst‐free electrophilic ring expansion of N‐unprotected aziridines and the ketene C=O double bond of α‐oxoketenes, in situ generated from the microwave‐assisted Wolff rearrangement of 2‐diazo‐1,3‐diketones. The ring expansion predominantly underwent an SN1 process and the hydrogen bond decides the (E)‐configuration of products.

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

“…On the basis of the experimental results and previous reports [21,22], the reaction mechanism is rationalized as following (Scheme 3). Under microwave heating, diazo esters 1 undergo a Wolff rearrangement to generate ethoxycarbonylketenes A by loss of nitrogen.…”

“…Interestingly, the reaction of α-diazo-β-diketones and 2-arylaziridines generated 2-(2-oxoalkylidene)oxazolidines [21],…”

“…Interestingly, the reaction of α-diazo-β-diketones and 2-arylaziridines generated 2-(2-oxoalkylidene)oxazolidines [ 21 ], while the current reaction of alkyl α-diazo-β-oxoalkanoates and 2-arylaziridines gave alkyl (oxazolin-2-yl)alkanoates as products, showing different chemoselectivities. 2-Alkylideneoxazolidines and 2-alkyloxazolines are structural isomers and can possibly tautomerize each other.…”

“…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.…”

“…They mainly include (1) cyclization of 2-amidoethyl halides or sulfonates, which are prepared from carboxylic acid derivatives and vicinal amino alcohols [ 8 – 10 ] ( Scheme 1a ); (2) direct condensation of carboxylic acid derivatives or nitriles with vicinal amino alcohols [ 13 – 15 ] ( Scheme 1a ); (3) oxidative condensation of aldehydes with vicinal amino alcohols [ 16 ] ( Scheme 1b ); (4) cyclization of N -allylamides in the presence of electrophilic reagents or radical initiators or catalysts [ 17 ] ( Scheme 1c ); (5) direct synthesis from alkenes and amides or nitriles in the presence of electrophilic reagents [ 18 – 19 ] ( Scheme 1d ). 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.…”