chiral carbene ligand, (S,S)-4, was evaluated with acetate as
the base. Pretreatment of dimer (S,S)-8 with silver acetate
led to replacement of the chlorides and gave a competent
catalyst. As expected, the complex with the (S,S)-ligand
preferentially oxidized the same enantiomer of alcohol as
oxidations using (-)-sparteine.
Table 2. Use of Achiral Pd(II) Dimers in Oxidative Kinetic
Resolution
In conclusion, both achiral and chiral N-heterocyclic
carbene ligands in conjunction with a chiral base, (-)-
sparteine, are effective for the Pd(II)-catalyzed aerobic
oxidative kinetic resolution of secondary alcohols. A general
synthesis of 1:1 PdCl2-carbene complexes has been devel-
oped that is amenable to an array of carbene ligands and
has potential applications in a variety of Pd(II)-catalyzed
processes.22 The potential of these complexes in aerobic
oxidations is highlighted by the use of a chiral Pd(II) complex
and the chiral base (-)-sparteine to enhance the kinetic
resolution of a racemic alcohol. Continued investigation into
the nature of ligand/base interactions toward an improved
oxidative kinetic resolution catalyst system as well as
application of this approach to new reaction types will be
reported in due course.
a
entry
dimer
R
% conversion (% ee)a
krel
1
2
3
4b
5b
5
5
5
6
7
C6H5
64.7 (96.0)
52.7 (65.9)
42.8 (58.2)
36.2 (34.9)
45.0 (54.1)
11.6
7.8
14.3
6.1
2-naphthyl
p-MeOC6H4
C6H5
C6H5
6.4
a Average of multiple experiments. b Conditions: 2.5 mol % dimer, 20
mol % (-)-sparteine.
Both enantiomers of 8 were evaluated in the oxidative
kinetic resolution of an alcohol using (-)-sparteine as the
base (Table 3).21 Use of enantiomeric complexes allowed
Acknowledgment. This work was supported by the
National Institutes of Health (NIGMS #RO1 GM63540) and
supported by a Research Innovation Award sponsored by
Research Corporation. D.R.J. is supported by an ACS
Division of Organic Chemistry Graduate Fellowship spon-
sored by Schering-Plough Research Institute. The crystal
structure analysis was performed by Atta Arif. We thank
Professor Steven Nolan for helpful discussions and initial
supplies of various carbene salts.
Table 3. Use of Chiral Pd(II) Dimers in Oxidative Kinetic
Resolution
% conversion (% ee)a
krel
a
entry
dimer
additive
1
2
3b
(R,R)-8 (-)-sparteinec
39.7 (36.4)
34.6 (42.0)
34.5 (10.2)
4.5
11.8
1.6
Supporting Information Available: Experimental pro-
cedures and characterization data. This material is available
(S,S)-8
(-)-sparteinec
(S,S)-8
AgOAcd
a Average of multiple experiments. b Toluene used as
c Sparteine (20 mol %). d AgOAc (10.5 mol %).
a
solvent.
OL027190Y
(18) Achiral and meso additives have been used with an enantiopure
ligand; for an example, see: Costa, A. M.; Jimeno, C.; Gavenonis, J.;
Carroll, P. J.; Walsh, P. J. J. Am. Chem. Soc. 2002, 124, 6929.
(19) For the use of achiral ligands with chiral conformations, see: (a)
Hashihayata, T.; Ito, Y.; Katsuki, T. Synlett 1996, 1079-1081. (b)
Hashihayata, T.; Ito, Y.; Katsuki, T. Tetrahedron 1997, 53, 9541-9552.
(c) Miura, K.; Katsuki, T. Synlett 1999, 783-785. (d) Mikami, K.; Korenaga,
T.; Terada, M.; Ohkuma, T.; Pham, T.; Noyori, R. Angew. Chem., Int. Ed.
1999, 38, 495-497. (e) Balsells, J.; Walsh, P. J. J. Am. Chem. Soc. 2000,
122, 1802-1803.
(20) For a review of achiral additives in asymmetric catalysis, see: (a)
Vogl, E. M.; Gro¨ger, H.; Shibasaki, M. Angew. Chem., Int. Ed. 1999, 38,
1570. (b) For a specific example where a reversal in enantiofacial selectivity
was observed by addition of an achiral additive, see: Kobayashi, S.; Ishitani,
H. J. Am. Chem. Soc. 1994, 116, 4083.
the exploration of “matched” and “mismatched” diastereo-
meric interactions between the chiral ligand and (-)-
sparteine. A significantly higher krel value of 11.8 was
observed for catalyst (S,S)-8 versus (R,R)-8. This observation
of a matched interaction showcases the approach outlined
in Scheme 1 in which the chiral ligand and chiral base can
act in concert to enhance the kinetic resolution.
To further highlight the contribution of the ligand in the
matched oxidative kinetic resolution, a Pd complex with the
(21) For the use of similar chiral carbene ligands, see: Seiders, T. J.;
Ward, D. W.; Grubbs, R. H. Org. Lett. 2001, 3, 3225.
(22) For examples of the use of 1:1 Pd-carbene complexes in catalysis,
see: (a) Hillier, A. C.; Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.;
Nolan, S. P. J. Organomet. Chem. 2002, 653, 69. (b) Lee, S.; Hartwig, J.
F. J. Org. Chem. 2001, 66, 3402.
(16) (-)-Sparteine could act as a transient ligand, a base, or both.
(17) Asymmetric catalysis has been accomplished with a racemic catalyst
and an enantiopure activator; for an example, see: Mikami, K.; Terada,
M.; Korenaga, T.; Matsumoto, Y.; Ueki, M.; Angelaud, R. Angew. Chem.,
Int. Ed. 2000, 39, 3532.
Org. Lett., Vol. 5, No. 1, 2003
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