Quinuclidines reactions with phosphates

Benzyl phosphates are less readily attacked by nucleophiles than methyl phosphates and they are more stable towards acidolysis than rm-butyl phosphates Benzyl phosphates are often used in complex polyfunctional targets because they are easily removed by hydrogenolysis. An indication of the reduced reactivity of benzyl phosphates is given in Scheme 7.17.32 Reaction of the phospho-nate diester 17.1 with one equivalent of 1 4-diazabicyclo[2 2 2]octane (DABCO) in refluxing toluene afforded the mono-deprotected derivative 17.2 in quantitative yield. Quinuclidine can also be used as the nucleophile. Assisted cleavage of benzyl phosphates is exemplified by the deprotection of the Shikimic Acid derivative in Scheme 7.18 using bromotrimethylsilane.33 34... 

The answer to this question only became apparent when it was observed that the reactions of substituted quinuclidines with 2,4-dinitrophenyl phosphate, p-nitrophenyl phosphate and phosphorylated pyridine show a decrease in rate with increasing basicity of the attacking quinuclidine (77). These second-order reactions clearly cannot have a negative amount of bond formation with the nucleophile in the transition state, so that this result forced us to think harder about what could cause zero or negative slopes in Br0nsted-type plots against the pK of the nucleophile. 

Figure 1. Br0nsted-type plots for the reactions of substituted quinuclidines with the dianions of 2,4-dinitrophenyl phosphate complexed with calcium (upper line), 2,4-dinitrophenyl phosphate (middle line), and p-nitrophenyl phosphate (lower line) at 39 °C, ionic strength 1.0 (KCl) ( ) and ionic strength 1.5 (KCl) (o) (Reproduced from reference 12. Copyright 1986 American Chemical Society.)...

Very similar results are found for reactions of quinuclidines with phos-phorylated pyridine, which follow a Brpnsted slope of Pnuc = —0.1. The less reactive phosphorylated 4-morpholinopyridine follows a slope of (3nuc = -0.01 (12). The changes in (3nuc for these phosphorylated pyridines and phosphate esters with a poorer leaving group (lg) represent Hammond effects that are described by the cross-interaction coefficient, pxy, of equation 3. This cross coefficient is larger than the direct coefficient that describes... 

These results are consistent with the observation that increasing basicity leads to a more favorable solvation energy for transfer of pyridines from the gas phase to water. The available data are consistent with a value of d for desolvation of approximately —0.2 (10, 13-16). The observed P value of — 0.1 for the reactions of quinuclidines with 2,4-dinitrophenyl phosphate and phosphorylated pyridine would then reflect the difference between the value of Pd = —0.2 and a value of Pnuc = 0.1 for the bond-forming step (equation 2). 

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