Chemistry Reference
In-Depth Information
Figure 6.14
Lewis acid and nucleophile activation in stereoselective reactions.
In addition to the above hydrolysis reactions, dinuclear approach to providing joint
Lewis acid activation and nucleophile activation has been applied to other organic re-
actions (Figure 6.14) including stereoselective ring-opening of epoxides (
18
) [65, 66],
stereoselective aldol condensation (
19
) [67, 68], and stereoselective reduction (
20
) re-
actions [69].
6.7
Double Lewis Acid Activation
Single Lewis acid activation provides substantially greater rate acceleration for the hy-
drolysis of carboxyl esters [70], amides [35-37], and nitriles [38] than for the hydrolysis
of phosphate diesters [55]. The rates for hydroxide-catalyzed hydrolysis of esters,
amides and nitriles coordinated to Co(
III
) complexes are 10
4
-to10
6
-fold greater
than those for hydroxide-catalyzed hydrolysis of the corresponding free substrates
(Figure 6.4). Sargeson's research team showed that the rate of hydroxide-catalyzed hy-
drolysis of a phosphate diester that is coordinated to a Co(
III
) complex is only about 50
times greater than that of the uncoordinated diester [55]. They also showed that the
hydroxide rate for the hydrolysis of a phosphate triester that is coordinated to a Co(
III
)
complex is about 400 times greater than that for the hydrolysis of the uncoordinated
triester [39]. Unfortunately, single Lewis acid activation provides the least rate accel-
eration for the most stable substrate (Table 6.1). The developing negative charge in the
single Lewis acid activated phosphate diester cleavage reaction (Figure 6.15) is not
stabilized by direct coordination (
21
) as it is in the single Lewis acid activated phos-
phate triester hydrolysis (
22
) (or in the single Lewis acid activated ester, amide or nitrile
hydrolysis). The developing negative charge in phosphate diester hydrolysis could be
stabilized by coordinating both phosphoryl oxygens to one or two metal ions (
23
).
Phosphates bridge dinuclear metal centers in the active sites of some phosphoes-
terases [1-3]. Dinuclear metal complexes should be able to provide double Lewis acid
activation for hydrolyzing phosphates. To quantify double Lewis acid activation for
cleaving phosphate diesters, we studied the reaction of
24
(Figure 6.16), which has
