Chiral [16]-ane P4N2 macrocycles: stereoselective synthesis and unexpected intermolecular exchange of endocyclic fragments

Abstract

Chiral 1,9-diaza-3,7,11,15-tetraphosphacyclohexadecanes were stereoselectively synthesized as pure R_PS_PS_PR_P isomers via a one-pot Mannich-type condensation reaction of 1,3-bis(arylphosphino)propane, formaldehyde and optically active, as well as racemic, primary amines. An unprecedented intermolecular exchange of endocyclic amino fragments of 1,9-diaza-3,7,11,15-tetraphosphacyclohexadecanes was observed. The lability of the P–CH₂–N fragment in macrocyclic aminomethylphosphines is the reason of the stereoisomerization, formation of products with medium-sized cycles as well as the exchange of endocyclic amino fragments. The mechanism of these transformations involving the formation of a methylenephosphonium intermediate and further intra- and intermolecular nucleophilic substitution is discussed.