Chemical Science
Edge Article
Table 2 Results of the substrate investigationa
cyclopropanation of a-diazo-b-keto sulfones. Additionally, this
study represents, to the best of our knowledge, the rst copper
catalyzed asymmetric cyclopropanation in water.58 Even though
O–H bond insertion is a major side reaction for copper–car-
benes in water, these results do demonstrate for the rst time
that enantioselective organometallic catalysis is feasible using
the DNA-based asymmetric catalysis concept. Thus, this study
unequivocally demonstrates that DNA-based catalysis can be
expanded beyond Lewis acid catalyzed reactions and provides a
promising basis for further explorations of DNA–metal-hybrid
catalysts for synthetically important transformations in water.
Entry
Substrate
Conversionb [%]
Yieldb [%]
eeb [%]
1
2
1c
1d
1e
1e
1f
78
26
n.d.
n.d.
n.d.
n.d.
0
0
2
40
13
29
n.d.
n.d.
n.d.
16
3c
4c,d
5c
6c
51
1g
63 (1R,5R)
a
The experiments were carried out in a glove box, with 1 mM 1a, 1.5 mM
base pairs of st-DNA, 30 mol% (0.30 mM) of Cu(NO3)2 and 0.30 mM of
L5a mixed in DMF prior to the reaction, in 10 mM of deoxygenated
MOPS buffer (pH 6.5), 2% v/v DMF, for 3 days at room temperature,
b
unless otherwise specied. n.d. ¼ not determined. Conversions,
yields and enantioselectivities are based on areas of HPLC peaks that
are compared to methyl phenyl sulfone as external standard. All data
are averaged over two experiments. Reproducibility: ee values and
Acknowledgements
c
Financial support from the NRSC-Catalysis is gratefully
acknowledged.
yields ꢀ5%, conversions ꢀ10%. 30 mol% (0.30 mM) of Cu(NO3)2
and 0.60 mM of L5e mixed in DMF prior to the reaction. d With 2 mM
sodium ascorbate.
Notes and references
compete with the O–H bond insertion reaction. Additionally,
dppz derivatives were also the ligands with which the highest ee
values were achieved in the catalyzed reaction. These observa-
tions are in marked contrast with the previously reported DNA-
based CuII catalyzed C–C bond forming reactions in which the
complexes of weakly binding ligands that are not pure inter-
calators, such as bipyridines, always gave rise to higher activi-
ties and selectivities. A tentative explanation for this observed
difference is that in the present case, the kinetically stable and
structurally rigid stacking of the intercalating ligands of the
copper complex between the base-pairs of the DNA results in a
microenvironment that limits access of surrounding water to
the catalytic site, i.e. the CuI–carbene complex. Thus cyclo-
propanation is favored compared to O–H insertion. Moreover,
the close proximity of the catalyzed reaction to the chiral DNA
helix results in an efficient transfer of chirality and, as a result,
high enantioselectivity in the product.
Secondly, in line with previous observations, it was found
that methyl substituents on selected positions of the ligand
resulted in higher enantioselectivities in the catalyzed reaction.
Strikingly, the relative positions of these methyl substituents
are the same as in ligand L2, which similarly gave signicantly
higher ee values compared to unsubstituted 2,20-bipyridine in
DNA-based Lewis acid catalyzed reactions.55 The reason for the
importance of methyl groups at these positions, which are
remote from where the catalysis occurs is intriguing but at
present not understood. Finally, the highest ee values were
obtained using ligand to copper ratios of 2 : 1. No, or only a
negligible increase of enantioselectivity was reported before for
CuI catalyzed insertion reactions with ligand to copper ratios
of 2 : 1.56,57
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