Synthesis of functionalized phenylalanine derivatives by ring opening reactions of 3‐arylaziridine‐2‐carboxylic esters

Ring-opening reactions of 3-arylaziridine-2-carboxylic esters with various nucleophiles are described. Racemic methyl 3-(4-methoxyphenyl)-, 3-phenyl- and 3-(4-nitrophenyl)aziridine-2-carboxylate (1a, 1b and 1c, respectively) were selected as substrates. In the absence of acid, no ring opening occurred. On treatment with ethereal hydrogen chloride, 1a gave a mixture of diastereomers 2a, whereas 1b and 1c gave mixtures of regioisomers 2b/3b and 2c/3c, respectively. Boron-trifluoride etherate catalyzed reaction of 1a with benzenethiol and indole also resulted in the formation of diastereomeric ring-opened products 4a and 6a, respectively, due to the electron-releasing properties of the p-methoxy group. Only C3 attack was observed. Under the same conditions, 1b and 1c gave a clean SN2-type ring opening, leading to diastereomerically pure products 4b, 4c, 6b and 6c. Reaction of 1b with acetic acid gave 7 in an SN2-type ring opening at C3, followed by an ON acyl shift. Treatment of enantiopure (+ )-(2S,3R)-1b with benzenethiol, indole and acetic acid gave the corresponding enantiomerically pure β-functionalized α-amino acid derivatives. Functionalization of 1b at nitrogen strongly increased the reactivity: N-acylaziridine 8 isomerized to trans-oxazoline 11 when treated with boron trifluoride etherate in acetonitrile.