Nucleophilic Reactions of 5-tert-Butyl-2-methoxy-3H-azepine with Alkoxides and Alkyllithium Reagents

The reaction of 5-tert-butyl-2-methoxy-3H-azepine (2a) with sodium alkoxides gave 2-alkoxy-3H-azepine derivatives 3-6 by nucleophilic transetherification. The treatment of 2a with tert-butyllithium also yielded 2,5-di-tert-butyl-3H-azepine (7); however, the reaction of 2a and methyllithium gave the expected 5-tert-butyl-2methyl-3H-azepine (8) along with unexpected 5-tert-butyl-2,2-dimethyl-2,3-dihydro-1H-azepine (9), but also 5,5ʹ-di(tert-butyl)-2,2ʹ-methylenedi(3H-azepine) (11), the structure of which was found to be tautomerized 5-tert-butyl-2-(5-tert-butyl-2,3-dihydro-1H-azepin-2-ylidenemethyl)-3H-azepine (12). The energy profile for the observed tautomerization is discussed based on ab initio DFT calculations and kinetic measurements.