Benzazirine azirine cyclization

A single o- or p-methyl substituent has no influence on the rate of cyclization of the singlet tolylnitrene to the favored azirine. ° The methyl group has no bystander effect on benzazirine formation. Cyclization of 2,6-dimethylphenyl or 2,4,6-tri-methylphenylnitrenes necessarily proceeds toward a carbon bearing a substituent. A steric effect raises the barrier to cyclization by 1.5-2.0 kcal/mol, in excellent agreement with the predictions of Karney and Borden. The steric effect extends the lifetime of 2,6-dimethylphenylnitrene at ambient temperature to 13 ns in Freon-113 and of 2,4,6-trimethylphenylnitrene to 8 ns, in the same solvent (Table 11.4). ° ... 

Curiously, the addition of a second orf/zo-fluorine substituent (i.e. in benzazirine 17d) raises the barrier to reversion to singlet nitrene 16d, relative to the mono orf/io-fluoro system (Fig. 14). This is partly due to steric hindrance by fluorine in the transition state for cyclization, but also to the stabilization of 17d by the fluorine attached directly to the azirine ring vide suprd)F The addition of the second fluorine substituent (benzazirine 17d) decreases the barrier to conversion of azirine 17d to ketenimine 18d slightly... 

Scheme 11.27 describes the rearrangement of 52 to 51 as one-slep reaction. However, the computational work of Kamey and Borden " demonstrates this to be a two-step process involving benzazirine 50, the species trapped by ethanethiol (Scheme 11.24). The first step, cyclization of 52 to the azirine 50, is predicted to be the rate-determining step (Scheme 11.28). The CASPT2 energetics of rearrangement is depicted in Figure 11.9.

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