Hydroacridines XVIII.: Synthesis and NMR spectroscopic investigation of (4aα,8aβ,9aα,10aβ)-tetradecahydroacridine and some of its derivatives

The reductive amination of (R*,R*)-2,2'-methylene-bis-cyclohexanone (1) with methylamine and potassium borohydride affords a mixture of (4a alpha,8a beta,9a alpha,10a beta)- and (4a alpha,8a alpha,9a beta,10a alpha)-tetradecahydro-10-methylacridine (2, 3) in a ratio of approximately 1.3:1 in 57% overall yield. By N-demethylation of 2, via the N-nitrosamine 4 the first synthesis of (4a alpha,8a beta,9a alpha,10a beta)-tetradecahydroacridine (5) could be performed. The relative configurations and conformations of compounds 2-5 as well as the barrier of conformational inversion of 5(Delta G(300)(#), = 55.5 +/- 0.4kJ.mol(-1)) were determined by NMR spectroscopy.