Regioselective, Lewis Acid-Catalyzed Ring-Openings of 2,3-Aziridyl Alcohols with Azoles

Methods for regioselective ring-opening reactions of <i>N</i>-sulfonyl-protected aziridyl alcohols with azole nucleophiles have been developed. Several classes of azoles, including indazole, substituted pyrazole, benzotriazole, and tetrazole, have been employed as reaction partners, giving rise to C3-selective opening and >3:1 <i>N</i>-selectivity. BF₃•OEt₂ is the optimal catalyst for most substrate combinations, although examples where diphenylborinic acid (Ph₂BOH) provides higher yields, or where the reactions proceed efficiently without a catalyst, are also described. Computational modeling of the BF₃•OEt₂-catalyzed reaction is consistent with the observed regiochemical outcome. The calculated ring-opening transition state appears to be stabilized by an unconventional OH···FB hydrogen-bonding interaction.