Synthesis and conformational analysis of saturated cis- and trans-1,3,2-benzodiazaphosphinine 2-oxides

By cyclization of N-unsubstituted, and N-1- or N-3-methyl-substituted cis- and trans-2-(aminomethyl)cyclohexylamines with phenylphosphonic dichloride, phenyl dichlorophosphate and bis(2-chloroethyl)phosphoramidic dichloride, P epimeric diastereomers a and b of the corresponding 1,3-unsubstituted and 1- or 3-methyl-substituted 2-phenyl-, 2phenoxy- and 2-[bis(2-chloroethyl)amino]decahydro-1,3,2-benzodiazaphosphinine 2-oxides have been synthesized. The stereochemistry and conformations of the prepared saturated 1,3,2-benzodiazaphosphinine 2-oxides were determined by H-1, C-13 and P-31 NMR spectroscopy aided by DFT geometry optimizations and J-coupling-constant calculations for selected structures. The 2-phenoxy-substituted transfused derivatives with an equatorial phenoxy group in a hypothetical double-chair conformation (14a, 16a, 18a) were observed to adopt nonchair heteroring conformations with a pseudoaxial P-OPh bond instead. The corresponding b epimers, as well as the trans-fused 2-phenyl and 2-[bis(2-chloroethyl)amino] derivatives (both P epimers) were found to retain double-chair conformations. In the cis-fused series, the position of the N-in/N-out equilibrium was dependent on the steric and stereo electronic requirements of the phosphorus substituents (and thus on the phosphorus configuration) as well as on the substituents at the ring nitrogen atoms.