Synthesis and resolution of diastereomers of (R,R)-1,2-cyclohexylenediamino-di-phenylmethylphosphonates

Salen-like compounds, such as bis-aminophosphonic systems bearing a (R,R)-1,2-diamino-cyclohexyl (DACH) moiety, were synthesized by the addition of dialkyl phosphites to the azomethine bond of N,N′-dibenzylidene-1,2-diaminocyclohexane 2. Five bis-aminophosphonates, dimethyl, diethyl, diisopropyl, dibenzyl, and diallyl derivatives, were obtained in high diastereoselectivity. Three of these compounds, dimethyl 3a, diethyl 3b, and diisopropyl 3c derivatives, had the predominant diastereoisomers separated. A hypothetical explanation of the diastereoselectivity is also reported.

Figure optionsDownload as PowerPoint slide

Tetraisopropyl (R,R)-1,2–cyclohexylenediamino-(S,S)-di-phenylmethylphosphonate[α]D20=-55.7 (c1, CH2Cl2)Absolute configuration: (R,R)(S,S)Source of chirality: (R,R)-1,2-diaminocyclohexane

Tetramethyl (R,R)-1,2–cyclohexylenediamino-(S,S)-di-phenylmethylphosphonate[α]D20=-74.5 (c 1, CH2Cl2)Absolute configuration: (R,R)(S,S)Source of chirality: (R,R)-1,2-diaminocyclohexane

Tetraethyl (R,R)-1,2–cyclohexylenediamino-di-(S,S)-phenylmethylphosphonate[α]D20=-69.4 (c 1, CH2Cl2)Absolute configuration: (R,R)(S,S)Source of chirality: (R,R)-1,2-diaminocyclohexane