Chemistry Reference
In-Depth Information
Figure 6.23 Metal hydroxide (34) and metal alkoxide (35) used for
cleaving phosphate diesters.
Metal hydroxide, metal alkoxide and oxide bridging two metal centers are all effec-
tive nucleophiles for cleaving phosphate diesters. Metal hydroxides provide compar-
able rate accelerations for hydrolyzing phosphate diesters with good or poor leaving
groups, yet metal alkoxides provide far greater rate acceleration for hydrolyzing phos-
phates with good leaving groups than for those with poor leaving groups. Thus,
6
pro-
vides a ca. 10 orders of magnitude rate acceleration for hydrolyzing bis-(p-nitrophe-
nyl)phosphate [53] and dimethyl phosphate [43]. The metal alkoxide in
35
(Figure 6.23)
is more reactive than the corresponding metal hydroxide (
34
) for cleaving phosphate
diesters with very good leaving groups (2,4-dinitrophenol) but the order of the reac-
tivity is reversed for cleaving phosphate diesters with poorer leaving groups (p-nitro-
phenol) [134].
Strongly basic nucleophiles rapidly cleave carboxyl esters with weakly basic leaving
groups [52]. The rate of displacement of strongly basic leaving groups with weakly
basic nucleophiles is very slow. Metal-alkoxides are too weakly basic to displace
strongly basic leaving groups such as methoxide yet they are basic enough to rapidly
displace weakly basic leaving groups like 2,4-dinitrophenolate. So why should metal
hydroxides provide comparable rate acceleration for hydrolyzing phosphates with good
or poor leaving groups? It appears that for cleaving phosphates with poor leaving
groups, a deprotonatable nucleophile (such as a metal hydroxide but not a metal alk-
oxide) is required. The expulsion of poor leaving groups (as in RNA and DNA hydro-
lysis without leaving-group activation) is probably accompanied by deprotonation of
the metal hydroxide (
36
) (Figure 6.24).
The phosphate diester in
37
(Figure 6.25) is cleaved about 11 orders of magnitude
more rapidly than the uncoordinated diester [72]. The mechanism of the reaction in-
volves nucleophilic attack of the bridging phosphate by the bridging oxide. Assuming
Figure 6.24 Deprotonatable metal hydroxide.
