A Superstable Nitrogen Pyramid: Stereodirected N-Halogenation of Methyl 2-Aziridinecarboxylate

Stereodynamics of Nitrogen Chiral Centers in aza‐β3‐Cyclodipeptides

“…High Δ G ≠ values are also observe in 2‐methoxy‐1,2‐oxazolidines where the nitrogen chiral center is connected to both endocyclic and exocyclic electronegative elements. It is worth noting that although the mechanism of enantiomerization of nitrogen in small heterocycles is most often considered as arising from hindered NPI, some studies suggest alternative pathways like ion pair formation in the case of N ‐chloro‐diaziridine or N ‐chloro‐oxaziridine, or a ring opening–ring closure mechanism for 1,2‐dipropyldiaziridines and 3,4‐diterbutyle‐1,3,4‐oxadiazolidines . On the whole, slow NPI remained for 60 years the quasi‐exclusive prerogative of small cyclic compounds (Fig.…”

N-Fluorination of aziridinecarboxylates via fluorolysis of their N-aminomethyl derivatives

“…

A new and convenient method for the synthesis of 1-fluoroaziridinecarboxylates through the fluorolysis of N-aminomethylaziridinecarboxylates is revealed.1-Fluoroaziridines show an extraordinarily high configurational stability of the nitrogen atom (∆G inv = 35 kcal mol -1 ) 1 but only a few of these scarcely available compounds have been reported. [1][2][3] They are obtained by addition of CH 2 N 2 to the N-fluoroimine of hexafluoroacetone followed by acidolysis of the resulting ∆ 2 -1,2,3-triazoline (yield 38%). 2,3 Later, 1-fluoro-2,2-bis(trifluoromethyl)aziridine was obtained by direct fluorination of 2,2-bis(trifluoromethyl)aziridine (F 2 /NaF) in 50% yield and its NMR parameters were refined.

…”

“…When this H-bond is broken in the presence of Et 3 N both isomers A and B are formed. 1 In the case of unsymmetrically-substituted aziridinecarboxylates this leads to fluorine attack from the more sterically hindered side with the formation of mostly N-fluoroaziridine C 6 or exclusively E. 7 However, fluorination of aziridines in the presence of NaF is difficult to reproduce and yields strongly depend on the reaction conditions (dispersivity of NaF, mixing conditions, dilution extent, rate of F 2 feed), and fluorination in the presence of Et 3 N is limited. Thus, methyl trans-2-trifluoromethylaziridine-3-carboxylate is far less nucleophilic than methyl aziridine-2-carboxylate and in the presence of Et 3 N it does not undergo fluorination because of the concurrent and easier fluorination of Et 3 N itself.…”

Derivatives of 1-fluoroaziridine-2,2-dicarboxylic acid

“…Synthesis of derivatives of aziridinecarboxylic acids with electronegative N-substituents, [1][2][3][4][5][6][7][8][9][10][11][12] such as 1-6 (∆G # inv / kcalmol -1 in parentheses) has been developed in our laboratory in connection with the investigation of asymmetric nitrogen.…”

“…It was shown that aziridine 6 has a record high configurational stability. 12 In this work, for the first time derivatives of 1-fluoroaziridine-2,2-dicarboxylic acid 10-14 have been synthesized and studied (Scheme 1). † Compound 10 was prepared by fluorination of dimethylaziridine-2,2-dicarboxylate.…”