Phosphates intramolecular transesterification

Bifunctional analogs of the [(CR)Zn]2+ (Fig. 6a) structure in which an auxiliary catalytic imidazole or thiophenol group has been incorporated (Fig. 40) exhibit enhanced reactivity for the intramolecular transesterification reaction of 2-hydro-xypropyl 4-nitrophenyl phosphate (HPNP) relative to the parent complex.222... 

Fig. 40 (top) Cationic portion of bifunctional zinc complexes and relative second-order rate constant values and (bottom) intramolecular transesterification reaction of 2-hydroxypropyl 4-nitrophenyl phosphate (HPNP). 

The intramolecular transesterification reaction of 2-hydroxypropyl 4-nittophenyl phosphate (243) (Scheme 44) was greatly accelerated (10 -10 -fold) by the addition of divalent metal ions such as Zn and Cu + in MeCN without a base the metal ion effect was found to be quite sensitive to the content of H2O in MeCN. ... 

Treatment of diphenyl chlorophosphate with primary or secondary alcohols in the presence of the Lewis acid, tris(pentafluorophenyl)boron B(QF5)3 was highly efficient for the preparation of phosphate triesters. The proposed mechanism envisioned the initial formation of a highly reactive boronate ester RO(BCgF5)2 that coordinated with the chlorophosphate, facilitating an intramolecular transesterification to yield the triesters." °... 

Compound 10 has also been used to quantify double Lewis acid activation by two cobalt (HI) ions [37]. In 12, the RNA analogue 2-hydroxypropyl-phenyl phosphate (HPPP) is coordinated to the dinu-clear cobalt site. It is well known that in this substrate the hydroxypropyl group is an efficient intramolecular nucleophile. Release of phenol by intramolecular cyclization is much faster than the reaction by nucleophilic attack of bridging oxide, as observed in 11. At pH >8, transesterification rate is linearly dependent on hydroxide concentration since OH" acts as an intermolecular base for the deprotonation of the hydroxypropyl group. The second order rate constant for the hydroxide-dependent cleavage is 4 x 105 times larger than the second-order rate constant for the hydroxide-dependent spontaneous transesterification of hy-droxypropyl-phenyl phosphate. 

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