In our ongoing research of CH₂N₂ application for synthesizing the MedChem relevant building blocks, we report their reaction with N-tert-butylsulfinyl imines of fluoral. Firstly, we found that the treatment of imine 1 by stoichiometrically non-controlled CH₂N₂ excess leads to the unexpected formation of triazoline 4, which structure was proved by X-ray. Triazoline 4 is a product of formal “methylation” of expected product 2 (Scheme 1). For the explanation of the results, we investigated the reaction in detail. The starting imine of fluoral (S)-1 reacts with diazomethane selectively at 0^oC to give the expected product of [3+2] – cycloaddition – triazoline 2. An increase in the temperature of the reaction mixture leads to the elimination of nitrogen with the formation of imine trifluoroacetone (S)-3. The latter was isolated by distillation in a preparative scale. It should be noted that this method of the synthesis of 3 is most convenient in comparison with previously reported. The subsequent interaction of imine (S)-3 with diazomethane occurs stereoselectively with the formation of optically pure triazoline (R,S_s)-4. X-ray analysis showed that the newly formed stereocenter has an R-configuration using imine 1 with an S-configuration on the sulfur atom. In the presence of trifluoroacetic acid triazoline (R,S_s)-4 can be cleanly converted into the respective aziridine (R,S_s)-5. Treatment of aziridine 5 with hydrochloric acid results in ring opening, which is accompanied by deprotection of sulfinyl group with the formation of enantiomeric pure aminochloride (S)-6 (Scheme 1). All transformations for imine 1 with R-configuration occur in the same manner.
The further preparative perspectives of the obtained procedure will be discussed.

Scheme 1. Possible reaction pathway.

Roman Zakharko

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