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

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Abstract
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 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.