Nucleophiles of High Reactivity in Phosphoryl Transfer Reactions: a-Effect Compounds and Fluoride Ion'

The second-order rate constants for reactions of hydrogen peroxide, acetohydroxamate, and fluoride anions with phosphorylated pyridine monoanions (H20, 25 O C , ionic strength 1.5) are larger than those of "normal" oxygen nucleophiles of the same pK, by factors of 600-, 160-, and 30-fold, respectively. The values of {-&} = 0.70 and 0.86 for reactions of phosphorylated pyridines with hydrogen peroxide and fluoride anions are smaller than predicted by a plot of {-&} against the pK, of normal oxygen nucleophiles; however, they fit a plot of [-&g] against log k for the reactions of oxygen nucleophiles with a phosphorylated pyridine. Thus, the transition-state structure, as measured by (-&g}, follows the reactivity, not the basicity of the nucleophiles. This is consistent with a thermodynamic origin for at least some of the rate enhancements for the a-effect nucleophiles and fluoride ions, such that the ratio of the phosphorus to proton basicities is larger for hydrogen peroxide and fluoride ion than for normal oxygen bases; Le., the rate enhancements for these nucleophiles may reflect an enhanced thermodynamic affinity for the phosphoryl group that influences the stability and structure of the transition state. The observed changes in transition-state structure are not predicted for rate enhancements from hydrogen bonding in the transition state or from weak solvation of the a-effect nucleophile. "a-Effect" nucleophiles, which have a heteroatom adjacent to the nucleophilic atom, often react rapidly compared with "normal" oxygen or nitrogen bases of comparable pK, and have been found to have high reactivity with several phosphorus(1V) ~ubstrates."'~ The reason for this high reactivity has not been established, although several explanations have been proposed.24 We present data here that show that the rate constants and structure of the transition state, as measured by &, for the reactions of hydrogen peroxide ion, an a-effect nucleophile, and (!) This research was supported in part by grants from the National Institutes of Health (Grant Nos. GM20888 and 4-61271) and the National Science Foundation (Grant No. PCM-8117816). D.H. was also supported by a fellowship from the Gillette Foundation. (2) For reviews, see: Hoz, S.; Buncel, E. Isr. J. Chem. 1985,26,313-319 and ref 3 and 4. (3) Edwards, J. 0.; Pearson, R. G. J . Am. Chem. SOC. 1%2,84, 16-24. Fina, N. J.; Edwards, J. 0. fnr. J . Chem. Kiner. 1973, 5, 1-26. (4) (a) Jencks, W. P. Catalysis in Chemistry and Enzymology; Mdjraw Hill: New York, 1969; pp 107-1 11. (b) Grekov, A. P.; Veselov., V. Ya. Russ. Chem. Rev. 1978.47, 631-648. (c) Hudson, R. F. In Chemical Reactivity and Reacrion Parhs; Klopman, G., Ed.; Wiley: New York, 1974; pp 203-220. ( 5 ) Hackley, B. E., Jr.; Plapinger, R.; Stolberg, M.; Wagner-Jauregg, T. J . Am. Chem. Soc. 1955,77,3651-3653. Green, A. L.; Saville, B. J . Chem. SOC. 1956,3887-3892. Stolberg, M. A.; Mosher, W. A. J . Am. Chem. SOC. 1957, 79, 2618-2620. Green, A. L.; Sainsbury, G. L.; Saville, B.; Stansfield, M. J . Chem. Soc. 1958, 1583-1587. Swidler, R.; Plapinger, R. E.; Steinberg, G. M. J . Am. Chem. SOC. 1959,81, 3271-3274. Endres, G. F.; Epstein, J. J . Org. Chem. 1959.24, 1497-1501. Aksnes, G. Acta Chem. Scand. 1960, 14, 1515-1525. Miller, B. J . Am. Chem. Soc. 1962,84,403-409. Moss, R. A.; Kim, K. Y.; Swarup, S. J. Am. Chem. SOC. 1986,108,788-793. Moss, R. A.; Wilk, 9.; Krogh-Jespersen, K.; Blair, J. T.; Westbrook, J. D. J . Am. Chem. SOC. 1989, 1 1 1 , 250-258. (6) Epstein, J.; Demek, M. M.; Rosenblatt, D. H. J . Org. Chem. 1956, 21, 796-797. Larsson, L. Acta Chem. Scand. 1958, 12, 723-730. (7) Rowell, R.; Gorenstein, D. G. J . Am. Chem. SOC. 1981, 103, (8) Kirby, A. J.; Younas, M. J . Chem. Soc. E 1970, 1165-1172. (9) Behrman, E. J.; Bialles, M. J.; Brass, H. J.; Edwards, J. 0.; Isah, M. J. Org. Chem. 1970, 35, 3069-3075. (10) Dostrovsky, I.; Halmann, M. J . Chem. Soc. 1965,87,553-559. Brass, H. J.; Bender, M. L. J. Am. Chem. Soc. 1972,94,7421-7428. Khan, S. A.; Kirby, A. J. J . Chem. Soc. B 1970,1172-1 182. Gorenstein, D. G.; Lee, Y . 4 . J. Am. Chem. SOC. 1977, 99, 2258-2263. (11) Kirby, A. J.; Jencks, W. P. J. Am. Chem. Soc. 1965,87,3209-3216. Kirby, A. J.; Varvoglis, A. G. J. Chem. Soc. E 1968, 135-141. (12) DiSabato, G.; Jencks, W. P. J. Am. Chem. Soc. 1%1,83,4393-4400. Bunton, C. A., Robinson, L. J . Org. Chem. 1969, 34, 773-780. (13) Jencks, W. P.; Gilchrist, M. J . Am. Chem. Soc. 1%5.87,3199-3209. Bourne, N.; Williams, A. J. Am. Chem. Soc. 1984, 106, 7591-7596. (14) There is a small rate enhancement for reactions of nitrogen a-effect bases at phosphorus with some substrates (ref 11 and 13) and not with others (ref 15). 5894-5902. 0002-7863 /90/ 15 12-195 1$02.50/0 Table I. Second-Order Rate Constants for the Reactions of Nucleophiles with Monoanions of PhosDhorylated Pyridines"