DNA AS A TOOL FOR MOLECULAR DISCOVERY - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 545

O

N

OCOMe [Ir(C 2 H 4 ) 2 CL] 2

Ligand (L 1 , L 2 )

OCOMe

O

(±) *

+ +

H H 2 O/Dioxane

MeO MeO

ee = -27% with L 1
ee = +28% with L 2

L 1 L 2

FIGURE 16.9

Allylic amination involving a DNA/diene/iridium hybrid catalyst.

incorporate a small-molecule catalyst anchored in a covalent, dative, or noncovalent
yet kinetically stable fashion to the DNA.
The covalent approach was explored by Jaschke and coworkers, who demon-
strated the influence of the DNA template on the stereochemical outcome of the
iridium-catalyzed kinetic resolution of phenyl allyl acetates. Indeed, by performing
the reaction using a DNA/iridium/chiral diene hybrid, the authors observed a
complete reversal of selectivity compared to the reaction run with the iridium/chiral
diene complex itself (Figure 16.9) [61].
By modifying one uridine nucleotide in an oligonucleotidic sequence,
Kamer and coworkers were able to develop a diphenylphosphine-containing
DNA that was successfully used in an asymmetric Pd-catalyzed allylic amination
(Figure 16.10) [62].
To date, a few examples of nonchiral ligands bound to DNA in a noncovalent
fashion have been used in asymmetric catalysis. The first one was developed by
Roelfes and Feringa in 2005 and consisted of a catalytically active copper(II)
complex linked to a DNA-intercalating 9-aminoacridine by a spacer (Figure 16.11)
[63]. This biohybrid was initially used to catalyze an asymmetric Diels-Alder
reaction between cyclopentadiene and various aza-chalcones; however, it was also
involved in various asymmetric conjugate additions [64], Friedel-Crafts reactions
[65a], epoxide resolutions [66], and in the syn -hydration of enones [65b]
(Figure 16.12). As a general trend, the results obtained in the presence of salmon
testes and calf thymus DNA indicate that the enantioselectivity is highly dependent
on the ligand employed and on the length of the spacer, while neither the catalyst to
substrate ratio nor the source of DNA drastically affects the outcome of the
reaction [63,67-69].
This promising approach inspired several other research groups to investigate
further the transfer of the stereochemical information of the DNA double helix to
small-molecules substrates in asymmetric fluorinations (Figure 16.13) [70],
aldolizations [71], or Henry [72] reactions but has so far been limited to the use
of Cu(II) ions.