5824
J. Am. Chem. Soc. 1998, 120, 5824-5825
C2-Symmetric Copper(II) Complexes as Chiral Lewis
Acids. Enantioselective Catalysis of the
Glyoxylate-Ene Reaction
6 2
Initial experiments revealed that [Cu((S,S)-t-Bu-box)](SbF )
complex (1)5 (10 mol %, CH
c
Cl , 0 °C) promotes the addition
2 2
of methylenecyclohexane to ethyl glyoxylate (eq 1) to afford (S)-4
in high enantioselectivity and yield (97% ee, 0 °C, <3 h, 97%
yield). In addition, we prepared the bis(aquo) complex [Cu((S,S)-
David A. Evans,* Christopher S. Burgey, Nick A. Paras,
Tomas Vojkovsky, and Steven W. Tregay
2 2 6 2
t-Bu-box)(H O) ](SbF ) (2), a blue solid that is readily obtained
8
from solutions of 1 exposed to water. This complex is an equally
effective catalyst with only a slight decrease in reaction rate
relative to the anhydro complex 1 (eq 1, 97% ee, 0 °C, <6 h,
Department of Chemistry & Chemical Biology,
HarVard UniVersity, Cambridge, Massachusetts 02138
9
7%). Concurrently, it was discovered that the [Cu((S,S)-Ph-
ReceiVed February 18, 1998
box)](OTf) complex (3) is also an excellent catalyst for this
2
9
reaction (eq 1, 87% ee, 0 °C, 99% yield); however, the absolute
stereochemistry of the resulting product (R)-4 is the opposite to
that produced by (S,S)-t-Bu-box catalysts 1 and 2 (vide infra).
Accordingly, either enantiomer of 4 may be obtained from a single
enantiomeric ligand series.
The development of enantioselective Lewis acid catalyzed
carbonyl addition reactions of π-nucleophiles such as enolsilanes
1
and allylstannanes is a topic of current interest. The extension
of this general process to include simple olefinic nucleophiles
2
via the carbonyl-ene reaction has important practical implications.
The practical advantages associated with the use of the bis-
(aquo) Cu(II)-box complex 2, as a readily prepared bench-stable
solid, prompted us to select this catalyst for development. The
reaction of ethyl glyoxylate with methylenecyclohexane (eq 1)
catalyzed by 2 was found to proceed with catalyst loadings as
low as 0.1 mol % without significant loss in enantioselectivity
or yield (CH Cl , 0 °C, 24 h, g90% yield, 94% ee). This reaction
In this context, Mikami and Nakai have reported a catalytic
3
enantioselective ene reaction with glyoxylate esters; however,
4
due to the limiting reactivity of the catalyst-glyoxylate complex,
only nucleophilic 1,1-disubstituted olefins may be employed.
We have recently reported that bidentate bis(oxazolinyl) (box)
Cu(II) complexes 1-3 are effective enantioselective catalysts in
5
6
Diels-Alder and aldol reactions with substrates that can parti-
2
2
may also be conducted in other solvents such as toluene and
diethyl ether with no loss in enantioselectivity.
cipate in catalyst chelation. In this study, we demonstrate that
The scope of the reaction of ethyl glyoxylate with other olefins
has been investigated (Table 1). The t-Bu-box complex 2 (1 mol
2 2
%, CH Cl , 0 °C) afforded excellent enantioselectivities and yields
in the reactions of ethyl glyoxylate with isobutylene (5: 96%
ee), R-methylstyrene (6: 93% ee), and methylenecyclopentane
(
7: 96% ee).10 Catalyst 3 (10 mol %, CH
2 2
Cl , 0 °C) also provided
the corresponding (R) R-hydroxy esters with good to excellent
enantiocontrol and yield (5, 92% ee; 6, 89% ee; 7, 76% ee).
The box-Cu(II) complexes can also be employed to catalyze
additions of unsymmetrical 1,1-disubstituted olefins to ethyl
glyoxylate. To realize a regioselective process in this reaction
the catalyst must be capable of discriminating between methyl
and methylene groups at the two possible reaction centers. The
addition of 2-methyl-1-heptene to ethyl glyoxylate catalyzed by
2 proceeds with excellent enantioselectivity to yield (S)-8 (96%
ee); however, the regioselectivity is only 74:26. In contrast, the
these chiral Cu(II)-based Lewis acids also catalyze the enantio-
selective addition of a variety of olefins to glyoxylate esters to
provide R-hydroxy esters, versatile synthons in organic synthesis.
The greater reactivity of these catalysts significantly extends the
scope of this process.
7
(S)-Ph-box-derived catalyst 3 mediates the process with superior
regioselectivity (90:10) while maintaining high enantioselectivity
to provide the enantiomeric adduct (R)-8 (91% ee). In previous
studies, this level of regioselectivity has not been obtained with
this enophile.2 Functionalized 1,1-disubstituted olefins, such as
silyl and benzyl-protected methallyl alcohol derivatives, also react
with ethyl glyoxylate in the presence of the Cu(II) catalysts to
yield 9 and 10, respectively, uncontaminated by regioisomeric
byproducts.
(
1) For leading references, see: (a) Bach, T. Angew. Chem., Int. Ed. Engl.
1
994, 33, 417-419. (b) Duthaler, R. O.; Hafner, A. Angew. Chem., Int. Ed.
,3
Engl. 1997, 36, 43-45. (c) For a comprehensive review of catalytic
enantioselective aldol reactions, see: Nelson, S. G. Tetrahedron: Asymmetry
1
998, 9, 357-389.
(2) For a general review of enantioselective ene reactions, see: (a) Mikami,
K.; Shimizu, M. Chem. ReV. 1992, 92, 1021-1050. Yamamoto has also
reported a catalytic ene reaction with 1,1-disubstituted olefins: (b) Mauruoka,
K.; Hoshino, Y.; Shirasaka, T.; Yamamoto, H. Tetrahedron Lett. 1988, 29,
3
967-3970. Chiral glyoxylate esters in ene reactions: (c) Whitesell, J. K.;
(7) For hetero Diels-Alder reactions employing glyoxylate esters and
metal-box complexes, see: (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.; Jørgensen, K. A. J. Chem. Soc., Perkin Trans. 2 1997, 1183-1185.
(8) The X-ray structure of complex 2 reveals a distorted square planar
Bhattacharya, A.; Buchanan, C. M.; Chen, H. H.; Deyo, D.; James, D.; Liu,
C.-L.; Minto, M. A. Tetrahedron 1986, 42, 2993-3001.
(3) (a) Mikami, K. Pure Appl. Chem. 1996, 68, 639-644. (b) Mikami, K.;
Terada, M.; Nakai, T. J. Am. Chem. Soc. 1990, 112, 3949-3954.
(
4) The structure of neither the active BINOLTiCl catalyst nor its
2
glyoxylate complex is known; however, recent speculation on the latter
structure has appeared: Corey, E. J.; Barnes-Seeman, D.; Lee, T. W.;
Goodman, S. N. Tetrahedron Lett. 1997, 38, 6513-6516 and references
therein.
2
copper center. The two H O-Cu-N-C dihedral angles are 30.0° and 36.0°.
The full details of this structure will be reported elsewhere.
(9) Other box-Cu(II) complexes afforded lower enantioselectivity: [Cu-
(t-Bu-box)](OTf)
(OTf)
ee), [Cu(Ph-box)](SbF
(10) In a representative procedure the catalyst solution (1 or 3) (0.05-
0.005 mmol in 1.5 mL of CH Cl ) is added in one portion to the olefin (0.50
2 2
(86% ee), [Cu(i-Pr-box)](OTf) (19% ee), [Cu(Bn-box)]-
(
5) (a) Evans, D. A.; Miller, S. J.; Lectka, T. J. Am. Chem. Soc. 1993,
2
(2% ee), [Cu(i-Pr-box)](SbF
6 2 6 2
) (36% ee), [Cu(Bn-box)](SbF ) (23%
1
15, 6460-6461. (b) Evans, D. A.; Lectka, T.; Miller, S. J. Tetrahedron Lett.
6 2
)
(70% ee).
1
993, 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)
2
2
Evans, D. A.; Johnson, J. S. J. Org. Chem. 1997, 62, 786-787.
mmol) and ethyl glyoxylate (3-10 equiv) at the indicated temperature (0 or
25 °C). After the reaction has proceeded to completion (1-48 h), the mixture
is directly loaded onto a 2 × 6 cm silica gel flash column and eluted with
hexanes/ethyl acetate to provide the R-hydroxy ester. With catalyst 2, the same
procedure is employed except that 2 is added as a solid to a solution of olefin
(6) (a) Evans, D. A.; Murry, J. A.; Kozlowski, M. C. J. Am. Chem. Soc.
1
996, 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. For Sn-
II)-box complexes as aldol catalysts, see: (c) Evans, D. A.; MacMillan, D.
W. C.; Campos, K. R. J. Am. Chem. Soc. 1997, 119, 10859-10860.
(
2 2
and glyoxylate (1.5 mL of CH Cl ).
S0002-7863(98)00549-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/28/1998