Supramolecular assistance to regioselectivity in the reactions of chlorocyclophosphazenes with sodium oxyanions: Macrocyclic effect and anion dependence

Comparative studies of the naphtholysis of crown-bearing tetrachlorocyclotr iphosphazene 2 and its acyclic analogue, nongem-diethoxytetrachlorocyclotri phosphazene 5 (which was synthesized and isolated in the pure cis form for the purpose of this study), reveal a significant macrocyclic effect of the substituent on both the kinetics and regiochemistry of chlorine substitutio n in the N3P3 ring. Whereas substitution of 5 with sodium naphthoxide provi ded moderate yields of the respective sterically and electronically favored nongem-naphthoxydiethoxy derivative as the major product, isolated as the mixture of cis and trans isomers 8 + 9, the corresponding reaction of crown substrate 2 resulted in highly regioselective formation of the gem-to-macr ocycle substituted mononaphthoxy PNP-crown derivative 11a. The importance o f the PNP-crown related effects for the regio- and stereocontrol of the sub stitution of chlorine atoms in the N3P3 ring is discussed in terms of supra molecular sodium cation-assisted interactions between the ring oxy substitu ent(s) and incoming oxyanions. To approach the problem of the anion-depende nce of the regioselectivity, a comparison has been drawn between the reacti ons of the PNP-crown substrate 2 with sodium arylates derived from beta -na phthol (10a) and phenol (10b), carried out with equimolar or 100% excess so dium oxyanion with respect to 2, and the corresponding reactions of 2 with sodium monoenolates derived from the beta -dicarbonyl compounds: acetylacet one (10c) and ethyl acetylacetate (10d). The effectiveness of supramolecula rly assisted transition state stabilization is found to be dependent not on ly on the dimensional complementarity between the cation and the macrocycle but also on the properties of the four interacting ionic centers according to the HSAB principle and on the nature of the electronic interaction of t he PNP-crown substituent with the N3P3 ring, the latter determining the ext ent of regiocontrol to either one or two macrocyclic chloride functions. Th e increase of the extent of regioselectivity of gem-substitution at the PNP -macrocycle when passing from arylate to beta -dicarbonyl enolate oxy anion s is related to the observed trends in the P-31 NMR chemical shifts and ref ers to the electronic structure of the oxy substituent.