Chiral Configurations of Cyclophosphazenes

Abstract

Tetracoordinated phosphorus atoms in derivatives of cyclophosphazenes are pentavalent and are potentially chiral. Chirality does not seem to have been investigated nor discussed for any literature examples of crystal structures of those cyclophosphazene compounds which are expected to be chiral. In cyclotriphosphazatriene compounds with ansa-substituted macrocyclic rings the two phosphorus atoms attached to the macrocycle are chiral, although the cis-ansa cyclotriphosphazatriene-macrocycle 1 is the meso form. Reaction of 1 with the di-secondary amine, piperazine, provides a convenient way to investigate the chiral configurational properties of cyclophosphazene compounds. It is found by X-ray crystallography that there are two configurational isomers (one meso and one racemate) of the singly bridged di(cyclophosphazene-macrocyclic) piperazine derivative 6i, and that there are two configurational isomers (both meso) of the doubly bridged di(cyclophosphazene-macrocyclic) piperazine derivative 8i; in 8i one meso form has a center of symmetry and the other a plane of symmetry. The chiral configurational properties of each stage of the reaction scheme for formation of 6i and 8i from 1 have been confirmed by 31 P NMR spectroscopy and the results are consistent with inversion of configuration at phosphorus at each step of the reaction of >P(OR)Cl groups with HNR′R′′ to form >P(OR)(NR′R′′) derivatives: viz. reaction of 1 with piperazine gives the monosubstituted compound 4i, which exists as a racemate with the macrocyclic ring in the trans-configuration; reaction of compound 4i with 1 gives the two configurational forms (meso and racemate) of the singly bridged derivative 6i with the macrocyclic rings in the trans-trans configuration; reaction of 6i with piperazine gives the monosubstituted singly bridged derivative 7i, which exists as two racemic mixtures with the macrocyclic rings in cis-trans configurations; and intramolecular condensation of 7i gives the two configurational forms of the doubly bridged derivative 8i with each of the macrocyclic rings in the cis-cis configuration. In this work the configurational properties of derivatives of cyclotriphosphazatriene rings with two (one N 3 P 3 unit) or four (two N 3 P 3 units) chiral centers have been rationalized. It is found that the chiral structures of cyclotriphosphazatriene derivatives may be represented by 2D molecular diagrams, as long as the Fischer rules for chiral carbon compounds are followed for phosphorus compounds.

Structural and stereogenic properties of spiro- and ansa-substituted 1,3-propanedioxy derivatives of a spermine-bridged cyclotriphosphazene

“…Although the possibility of optical isomerism in cyclophosphazene derivatives, [(NPXY) n n=3,4] was first discussed many years ago [1], chiral properties of molecules have only recently been elucidated [2][3][4][5] and used to investigate reaction mechanisms [6,7]. The spermine-bridged cyclophosphazene compound 1 has been prepared previously [8] by reaction of cyclotriphosphazene with the tetrafunctional amine, spermine.…”

Crystallographic Proof of Double Walden Inversion in Nucleophilic Substitution Reactions of Macrocyclic Cyclotriphosphazene Derivatives

“…[6] Instead of using changes in optical rotation to investigate reaction mechanisms involving inversion of configuration, we have used a different approach involving reactions of meso compounds to give racemates, which can react further to give either another meso compound or another racemate depending on the second substituent. [7,8] In recent years macrocyclic derivatives of cyclotriphosphazene have been isolated and X-ray crystallographic investigations of the initial products with polyether macrocyclic rings in the ansa configuration have been found, so far without exception, to have cis-ansa structures. [9,10] In macrocyclic cyclophosphazene compounds such as 1 (Scheme 1), the two P atoms carrying the macrocyclic ring, P(Om)Cl (where Om = macrocyclic residue), are stereogenic and, because compound 1 is symmetrically substituted, it is the meso form.…”

“…[9,10] In macrocyclic cyclophosphazene compounds such as 1 (Scheme 1), the two P atoms carrying the macrocyclic ring, P(Om)Cl (where Om = macrocyclic residue), are stereogenic and, because compound 1 is symmetrically substituted, it is the meso form. [7] The first reaction of compound 1 with a nucleophile (X -) takes place at either of the two P(Om)Cl groups to give the P(Om)X moiety, in which the macrocyclic ring now exists in a transansa configuration and the molecule is racemic. [7,8] Further reaction with the same nucleophile X -then converts the second P(Om)Cl group into another P(Om)X moiety and the resulting derivative has regained a cis-ansa structure and is meso again.…”

“…[7] The first reaction of compound 1 with a nucleophile (X -) takes place at either of the two P(Om)Cl groups to give the P(Om)X moiety, in which the macrocyclic ring now exists in a transansa configuration and the molecule is racemic. [7,8] Further reaction with the same nucleophile X -then converts the second P(Om)Cl group into another P(Om)X moiety and the resulting derivative has regained a cis-ansa structure and is meso again. [7] On the other hand, reaction of 1 with the first nucleophile X -and then further reaction with a different nucleophile Y -converts the second P(Om)Cl group into a P(Om)Y moiety and the resulting derivative has regained a cis-ansa structure, but is now racemic.…”

“…[7,8] Further reaction with the same nucleophile X -then converts the second P(Om)Cl group into another P(Om)X moiety and the resulting derivative has regained a cis-ansa structure and is meso again. [7] On the other hand, reaction of 1 with the first nucleophile X -and then further reaction with a different nucleophile Y -converts the second P(Om)Cl group into a P(Om)Y moiety and the resulting derivative has regained a cis-ansa structure, but is now racemic. [8] These structures have been confirmed crystallographically for single-bridged and double-bridged macrocyclic cyclophosphazene compounds, thus supporting the postulate of Walden inversions for both steps of the reaction.…”