114
Table 1A
Cyclopropanations using ligand 5.
Entry
Substrate
Diazoestera
% Conv.b
Turnover #c
Trans/Cis
% ee Transd
% ee Cisd
1
2
3
4
5
Styrene
Styrene
␣-Methylstyrene
␣-Phenylstyrene
Trans-stilbene
EDA
TBDA
EDA
EDA
EDA
93
81
86
85
20
929
807
858
847
202
1.9:1
4.6:1
3.3:1
–
84.3
74.4e
23.4e
23.8e,f
–
60.5
77.9
95.0
–
–
–
6
Cis-stilbene
EDA
22
220
16.8:1g
–
a
EDA, ethyldiazoacetate; TBDA, tert-butyldiazoacetate.
b
c
d
e
f
Determined by gas chromatography.
Calculated using the following equation: (mole olefin × % conversion)/mole catalyst.
Determined using a Chiralcel OJ HPLC analytical column and the % ee was corrected for the % ee of the ligand using the following equation: (observed ee/ligand ee) × 100.
Run using >99% (R)-5 to check validity of d.
Refers to exo/endo ratio.
g
Table 1B
Results using ligand 3 [14].
Entry
Substrate
Diazoester
% Conv.
Turnover#
Trans/cis
% ee Trans
% ee Cis
7
8
9
10
11
Styrene
Styrene
␣-Methylstyrene
␣-Phenyl styrene
Trans-stilbene
EDA
TBDA
EDA
EDA
96
96
91
93
39
960
960
910
930
390
2.4:1
5.9:1
1.8:1
–
27.4
40.5
18.2
9.5a
12.7
12.7
13.5
–
–
11.8a
–
a
The terms cis and trans are irrelevant.
reaction of ␣-phenylstyrene (Table 1A, entry 4), an ee of 74.4% was
obtained. When ␣-phenylstyrene was used as the substrate in the
catalytic cyclopropanation reaction using non-methylated ligand
3, the resulting cyclopropane product was obtained in less than
10% ee. It is clear from the results presented in Table 1A that the
ability of 5 to induce enantioselectivity in the cyclopropane prod-
ucts is a substantial improvement over ligands 1–4. It is possible
that the improved enantioselectivity in the cyclopropanation reac-
tion using ligand 5 could be due in part to the electronic effects of
the electron donating methyl substituent. However, the improved
enantiomeric induction of 5 is largely attributable to restricted
rotation about the cyclophane–nitrogen bond as discussed earlier.
orienting itself away from the catalytic copper center, allowing it
to efficiently transfer its chiral information to the resulting cyclo-
propane products.It is also worth noting that the conversions of
substrate to product were quite good when (R)-5 was used as the
ligand. Table 1A illustrates that conversions were typically >80% for
the styrene derivatives, with turnover numbers approaching 1000
(catalyst loading 0.1 mol%). The advantage of low catalyst load-
ings is that unwanted diazo coupling products are not detected
in these reactions. To the best of our knowledge this is the low-
est catalyst loading used for a salen-type ligand. Substituting the
propanation of styrene with EDA in the presence of Nozaki’s ligand
resulted in ee’s less than 10% for both the cis and trans cyclopropane
products [18], whereas salen ligands 3 and 5 resulted in much
improved enantioselectivities (Tables 1A, entry 1 and 1B, entry 7).
This shows that the simple chiral [2.2]paracyclophanyl moiety can
be much more effective in chiral induction compared to the chi-
ral phenethylamine unit of Nozaki’s ligand and is indicative of the
potential for the sterically demanding [2.2]paracyclophanyl unit to
construct highly effective chiral ligands for asymmetric catalysis.
2-hydroxyacetophenone and that 5 can be used as a ligand for
copper-catalyzed asymmetric cyclopropanation of styrene deriva-
tives. The simple substitution of a methyl group for the imine
hydrogen of 3 makes the cyclophane ligands much more effective
for asymmetric induction. Cyclopropanations of styrenes run using
5 as a ligand showed a dramatic average increase of 60% ee (2-
to 8-fold increases in % ee) compared to those run with ligand 3.
Ligand 5 was also less substrate sensitive with respect to enantios-
electivity while maintaining a good catalytic turnover. We have
grown crystals of ligands 3 and 5 and are currently carrying out X-
ray crystal structure analysis to obtain exact atom coordinates for
computational studies of the conformation differences between 3
and 5. These studies, together with spectroscopic studies of 3 and
5 in solution to elucidate the exact nature of the factors behind
the dramatic increase in asymmetric induction with ligand 5, are
ongoing.
Acknowledgments
The authors would like to thank Maureen Smith and Chaz Bur-
rows for technical assistance. Support from the Department of
Education, the National Science Foundation (MCB 0844478, CHE
0639208, CHE 0840390), the University of Oklahoma, and the Uni-
versity of Southern Mississippi is greatly appreciated.
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4. Conclusion
It has been demonstrated that
structed from commercially available [2.2]paracyclophane and
5 can be readily con-