C2-Symmetric Cu(II) Complexes as Chiral Lewis Acids
J. Am. Chem. Soc., Vol. 122, No. 33, 2000 7937
Figure 1. Calculated PM3 structure of [Cu((S,S)-t-Bu-box)(pyru-
vate)]2+
.
been observed in hetero-Diels-Alder reactions employing
glyoxylate esters and Cu(II)-box complexes.12 In the following
discussion, we demonstrate that these chiral complexes also
catalyze the enantioselective addition of a variety of olefins to
glyoxylate and pyruvate esters.13
enantioselective catalysts in the Diels-Alder,7 aldol,8 Michael,9
and amination10 reactions.11 In all of these processes, substrate-
catalyst chelation has afforded high levels of asymmetric
induction and predictable models for chirality transfer. The
cationic Cu(II) complexes such as [Cu(S,S)-tert-butylbis-
(oxazolinyl)](SbF6)2 (2a), are also considerably more Lewis
acidic than the general family of titanium(IV)-based Lewis acids,
[Ti(OR)2]Cl2, that have been used as ene and Diels-Alder
reaction catalysts.
Those reactions involving chelate activation of R-dicarbonyl
substrates by the Cu(II)-box catalyst (e.g. A, eq 1) are
particularly relevant to the present investigation. Aldol reactions
of pyruvate esters8c,d (eq 4) and hetero-Diels-Alder reactions
of â,γ-unsaturated R-keto esters7h (eq 5) both proceed in
Ene Reactions of Glyoxylate Esters
A preliminary evaluation of the ene reaction between meth-
ylenecyclohexane and ethyl glyoxylate at -78 °C revealed that
[Cu((S,S)-t-Bu-box)](OTf)2 (1a) promoted a highly selective ene
process; however, no catalyst turnover was observed. When the
reaction temperature was increased to 25 °C, the process became
catalytic in metal complex 1a with only modest loss of
enantioselectivity (eq 6). On the basis of this lead, this process
was employed for reaction optimization.
Reaction Optimization. Various Cu(II)-box complexes and
counterions were examined in the reaction of methylene
cyclohexane and ethyl glyoxylate (Table 1). The [Cu((S,S)-t-
Bu-box)](SbF6)2 complex 2a exhibited high reactivity affording
the ene products in excellent enantioselectivity. While the [Cu-
((S,S)-Ph-box)](OTf)2 complex 1c is also an excellent catalyst
for this reaction, the absolute stereochemistry of the resulting
product (R)-6 is opposite to that produced by (S,S)-t-Bu-box
catalysts 1a and 2a (vide infra). Accordingly, either enantiomer
of 6 may be obtained from a single enantiomeric ligand series.
The bis(aquo) complex [Cu((S,S)-t-Bu-box)(H2O)2](SbF6)2
(4), a bench-stable blue crystalline solid that is readily obtained
from solutions of 2a upon exposure to water, was also evaluated
as a reaction catalyst.14 This complex was also found to be an
effective catalyst for this reaction with only a slight decrease
in reaction rate relative to the anhydro complex 2a (eq 7: 97%,
96% ee, 25 °C, 1 h). Due to the practical advantages of [Cu-
excellent enantioselectivity in the presence of Cu(II)-box
catalysts. Catalyst-substrate complexes 5a and 5b have been
implicated as the species responsible for the observed enanti-
oselection (Figure 1). It is noteworthy that ene byproducts have
(7) (a) Evans, D. A.; Miller, S. J.; Lectka, T. J. Am. Chem. Soc. 1993,
115, 6460-6461. (b) Evans, D. A.; Lectka, T.; Miller, S. J. Tetrahedron
Lett. 1993, 34, 7027-7030. (c) Evans, D. A.; Murry, J. A.; von Matt, P.;
Norcross, R. D.; Miller, S. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 798-
800. (d) Evans, D. A.; Barnes, D. M. Tetrahedron Lett. 1997, 38, 57-58.
(e) Evans, D. A.; Miller, S. J.; Lectka, T.; von Matt, P. J. Am. Chem. Soc.
1999, 121, 7559-7573. (f) Evans, D. A.; Johnson, J. S. J. Org. Chem.
1997, 62, 786-787. (g) Evans, D. A.; Johnson, J. S. J. Am. Chem. Soc.
1998, 120, 4895-4896. (h) Evans, D. A.; Johnson, J. S.; Olhava, E. J. J.
Am. Chem. Soc. 2000, 122, 1635-1649.
(8) (a) Evans, D. A.; Murry, J. A.; Kozlowski, M. C. J. Am. Chem. Soc.
1996, 118, 5814-5815. (b) Evans, D. A.; Kozlowski, M. C.; Burgey, C.
S.; MacMillan, D. W. C. J. Am. Chem. Soc. 1997, 119, 7893-7894. (c)
Evans, D. A.; Kozlowski, M. C.; Murry, J. A.; Burgey, C. S.; Connell, B.
J. Am. Chem. Soc. 1999, 121, 669-685. (d) Evans, D. A.; Burgey, C. S.;
Kozlowski, M. C.; Tregay, S. W. J. Am. Chem. Soc. 1999, 121, 686-699.
For Sn(II)-box complexes as aldol catalysts see: (e) Evans, D. A.;
MacMillan, D. W. C.; Campos, K. R. J. Am. Chem. Soc. 1997, 119, 10859-
10860.
(9) (a) Evans, D. A.; Willis, M. C.; Johnston, J. N. Org. Lett. 1999, 1,
865-868. (b) Evans, D. A.; Rovis, T.; Kozlowski, M. C.; Tedrow, J. S. J.
Am. Chem. Soc. 1999, 121, 1994-1995.
(10) Evans, D. A.; Johnson, D. S. Org. Lett. 1999, 1, 595-598.
(11) For two recent reviews on various aspects of chiral Cu(2+) Lewis
acid-catalyzed processes see: (a) Evans, D. A.; Rovis, T.; Johnson, J. S.
Pure Appl. Chem, 1999, 71, 1407-1415. (b) Johnson, J. S.; Evans, D. A.
Acc. Chem. Res. 2000, 33, 325-335.
(12) (a) Johannsen, M.; Jørgensen, K. A. J. Org. Chem. 1995, 60, 5757-
5762. (b) Ghosh, A. K.; Mathivanan, P.; Cappiello, J.; Krishnan, K.
Tetrahedron: Asymmetry 1996, 7, 2165-2168. (c) Johannsen, M.; Jør-
gensen, K. A. J. Chem. Soc., Perkin Trans. 2 1997, 1183-1185. During
the course of this research two examples of Cu(II)-box catalyzed glyoxy-
late-ene reactions have appeared: (d) Gao, Y.; Lane-Bell, P.; Vederas, J.
C. J. Org. Chem. 1998, 63, 2133-2143. (e) Gethergood, N.; Jørgensen, K.
A. J. Chem. Soc., Chem. Commun. 1999, 1869-1870.
(13) A preliminary account of this work has appeared: Evans, D. A.;
Burgey, C. S.; Paras, N. A.; Vojkovsky, T.; Tregay; S. W. J. Am. Chem.
Soc. 1998, 120, 5824-5825.
(14) The X-ray structure of complex 4 reveals a distorted square-planar
copper center. The two H2O-Cu-N-C dihedral angles are 30.0° and 36.0°.
See: Evans, D. A.; Peterson, G. S.; Johnson, J. S.; Barnes, D. M.; Campos,
K. C.; Woerpel, K. A. J. Org. Chem. 1998, 63, 4541-4544.