A Theoretical and Experimental Study on Acid-Catalyzed Isomerization of 1-Acylaziridines to the Oxazolines. Reexamination of a Possible SNi Mechanism by Using ab Initio Molecular Orbital Calculations

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Abstract
The SNi mechanism, which was previously proposed for the isomerization of 1-acylaziridines to the oxazolines, was reexamined theoretically by performing molecular orbital (MO) calculations of 1-formylaziridine and its derivatives as model compounds and experimentally by using 1(R)-[α-methoxy-α-(trifluoromethyl)phenylacetyl]-2(S)-methylaziridine (5). At the MP2/6-31G**//RHF/6-31G* level, the activation energy was estimated to be 38.9 kcal mol-1 for the SNi mechanism in which N-protonated 1-formylaziridine 8a(NH+) isomerizes to the N-protonated oxazoline 9a(NH+). Intrinsic reaction coordinate calculations showed that this reaction proceeds with retention of the ring carbon configuration. Methyl substitution in the aziridine ring reduces the activation energy by 10 kcal mol-1. The ring closure of N-(2-chloroethyl)formamide (10a) to the oxazoline, which is a model reaction of the rate-determining step for the addition−elimination mechanism, was estimated to have an activation energy of 45.4 kcal mol-1. The results of these MO calculations are consistent with the observation that the isomerization of the acylaziridine 5 to the oxazoline 6 is facilitated in the presence of weak nucleophiles such as with BF3·OEt2 while the formation of 6 is very slow in the presence of stronger nucleophiles such as p-toluenesulfonate. Both theoretical and experimental results suggest that the SNi mechanism explains well the isomerization of (R,S)-5 to the oxazoline with BF3·OEt2 in refluxing benzene.