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

Article abstract of DOI:10.1002/recl.19921110102

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 S_N2-type ring opening, leading to diastereomerically pure products 4b, 4c, 6b and 6c.Reaction of 1b with acetic acid gave 7 in an S_N2-type ring opening at C3, followed by an O->N 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.