Chemistry Reference
In-Depth Information
Figure 6.6 Protonation vs. metal coordination.
show that a range of substrates can bind reasonably well to metal complexes even when
solvent water molecules can compete for coordination to the metal.
Lewis acid activation works particularly well for weakly basic substrates that bind
well to metal ions (Figure 6.6). Nitriles are excellent substrates for Lewis acid activation
since they are weakly basic (pK
a
of protonated acetonitrile is about -10) [42] yet they
bind well to metal ions (binding constant for acetonitrile to
6
is 2.5
M
-1
). Imines are
about fifteen orders of magnitude more basic than nitriles. Thus, in neutral aqueous
solutions, significant amounts of imines are protonated. Since protonated substrates
are generally more reactive than metal coordinated ones (Table 6.1), Lewis acid activa-
tion of imines with metal ions in aqueous solutions is difficult.
In addition to the above hydrolysis reactions, Lewis acid activation has been used to
carry out a range of stereoselective transformations. Many interesting chiral Lewis
acids have been developed over the past decade [21-25]. A single chiral Lewis acid
(
7
) has been shown to catalyze a wide variety of carbon-carbon bond forming reactions
(Figure 6.7) [22]. There is much current interest in developing such privileged catalysts
[21]. Solvent effects play an important role in Lewis acid activation. Both binding of
substrates and stabilization of oxyanionic transition states may be enhanced in organic
solvents.
Figure 6.7 A privileged chiral Lewis acid.
