A theoretical and experimental study on acid-catalyzed isomerization of 1-acylaziridines to the oxazolines. Reexamination of a possible S(N)i mechanism by using ab initio molecular orbital calculations

The S(N)i 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)-[alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl]-2-(S)-methylaziridine (5). At the MP2/6-31G**dagger>//RHF/6-31G* level, the activation energy was estimated to be 38.9 kcal mol(-1) for the S(N)i 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 S(N)i mechanism explains well the isomerization of(R,S)-5 to the oxazoline with BF3 . OEt2 in refluxing benzene.