Synthesis and Ring Opening of Methyl 2-Alkyl-3-(alkyl/aryl)-1-benzoylaziridine-2-carboxylates: Synthesis of Polysubstituted Amino Acids

Abstract

A new method for the preparation of 2,2,3‐trisubstituted methyl 1‐benzoylaziridine‐2‐carboxylates is reported. These compounds have been obtained starting from α‐alkyl β‐amino acids by formation of the lithium dianion and reaction with iodine. The aziridines undergo ring expansion or ring opening, depending on the substituents of the aziridine ring and on the reaction conditions. Following these methods, both α‐substituted α‐hydroxy β‐amino acids and α‐substituted β‐hydroxy α‐amino acids have been synthesised.

Lewis Acid-Catalyzed Diastereoselective Synthesis of Multisubstituted N-Acylaziridine-2-carboxamides from 2H-Azirines via Joullié–Ugi Three-Component Reaction

“…BF 3 •2H 2 O). 20 On the other hand, Nacylaziridines can rearrange into oxazolines, promoted under thermal, acidic or nucleophilic (eg. NaI) conditions.…”

“…13 C NMR (126 MHz, DMSO-d 6 ) δ 170. 6, 168.6, 162.6, 132.5, 128.9, 128.3, 126.1, 84.2, 78.9, 61.0, 50.3, 28.2, 27.2, 14.0 20 : To a solution of ethyl 1-benzoyl-3-(tertbutylcarbamoyl)-3-methylaziridine-2-carboxylate 4{1} (trans) or 5{1} (cis) (0.5 mmol, 166 mg) in DCM (10 mL) was added boron trifluoride dihydrate (1.5 mmol, 95 µL, 3 equiv) and the mixture was stirred for 6 h at room temperature. Upon completion of the reaction as indicated by TLC, saturated aqueous NaHCO 3 (15 mL) was added and extracted with DCM (2 x 15 mL).…”

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

“…The trans -imidazolidine 12b is a potential building block for foldamers, as the corresponding trans -oxazolidin-2-ones are already applied as such [46]. trans -Imidazolidine 12b could also be used as a precursor of the corresponding N α ,N β -deprotected α,β-diaminocarboxylamide, by hydrolysis under acidic conditions, in analogy with deprotection reactions of imidazolidines, imidazolines and oxazolines in the literature [16,47–48]. However, in a second reaction, syn -γ-chloro-α,β-diaminocarboxylamide syn - 5a was directly converted into the dihydrochloride of the N α ,N β -deprotected syn -γ-chloro-α,β-diaminocarboxylamide 13a , by stirring in 0.5 M (aq) HCl/EtOAc (2:1) for 30 min at rt, in a yield of 83%.…”

Aziridines in Formal [3+2] Cycloadditions: Synthesis of Five‐Membered Heterocycles

“…Several Lewis acids, including BF 3 ·OEt 2 , [21][22][23][24][25][26]28] Cu(OTf) 2 , [12] ZnX 2 (X = Cl, Br, I), [27] Zn(OTf) 2 , [28] Sc(OTf) 3 , [29] and Bi(OTf) 3 , [30] have been employed as catalysts in reactions of this type. Several Lewis acids, including BF 3 ·OEt 2 , [21][22][23][24][25][26]28] Cu(OTf) 2 , [12] ZnX 2 (X = Cl, Br, I), [27] Zn(OTf) 2 , [28] Sc(OTf) 3 , [29] and Bi(OTf) 3 , [30] have been employed as catalysts in reactions of this type.…”

“…[23] Some of the above limitations were successfully overcome by Singh and co-workers, who reported the formal [3+2] cycloadditions of N-tosylarylaziridines (e.g., 12a) with a range of nitriles, in the presence of BF 3 ·OEt 2 or Et 3 OBF 4 , at room temperature and with very short reaction times (Scheme 16). In this case, an 89:11 regioisomeric mixture of the cis-4,5-dihydro-1H-imidazoles rac-81a and rac-81b was obtained.…”