Palladium-catalyzed enantioselective oxidations of alcohols using molecular oxygen [27]

Full text of DOI:10.1021/ja015827n

J. Am. Chem. Soc. 2001, 123, 7475-7476
Table 1. Initial Screening
7475
Palladium-Catalyzed Enantioselective Oxidations of
Alcohols Using Molecular Oxygen
David R. Jensen, Jacob S. Pugsley, and Matthew S. Sigman*
Department of Chemistry
UniVersity of Utah
Salt Lake City, Utah 84112
ReceiVed March 15, 2001
ReVised Manuscript ReceiVed June 27, 2001
The use of molecular oxygen as a stoichiometric reoxidant in
combination with a catalytic metal has exceptional practical
advantages for applications in organic synthesis.1 This is in part
due to the favorable economics associated with molecular oxygen
and the formation of environmentally benign byproducts in the
oxidation manifold (water and hydrogen peroxide). An excellent
example of the use of molecular oxygen in organic synthesis is
the metal-catalyzed aerobic oxidation of alcohols to aldehydes
and ketones.2,3 We became interested in extending the scope of
these oxidations to asymmetric catalysis.4 To this end, we
envisioned two potentially useful reactions: (1) the oxidative
kinetic resolution of racemic secondary alcohols,5 kinetic resolu-
tions that have previously been accomplished using acylation6
and oxidation,7,8 and (2) the oxidative desymmetrization of meso-
diols.9 Herein we report a convenient, enantioselective aerobic
oxidation of alcohols mediated by Pd(II) and a chiral diamine.
Aerobic oxidations of alcohols using catalytic Pd(II) salts have
been reported.3a-d Of particular interest is the observation that
amine additives3a-c both effect ligand-accelerated catalysis10 and
extend the substrate scope. Therefore, we initiated our investiga-
a Ligand structures are available in the supporting info. b Conversion
determined using internal standard. c 5 mol % Ligand.
tion for an oxidative kinetic resolution catalyst by screening
various chiral amine ligands in addition to common ligands for
Pd-mediated asymmetric reactions (Table 1, eq 1). Bi- and
tridentate ligands were generally poor templates for oxidation
giving low conversions (entries b, f, g, and h). In contrast, Pd(II)
complexes derived from pyridine ligands with 3-substitution gave
high conversions, albeit with low krel values11 (entries c and e).
The most promising result from this initial screen was that (-)-
sparteine, a chiral tertiary diamine, gave the best krel (2.6).
To improve both the reaction rate and krel, the reaction
parameters of the (-)-sparteine/Pd(II) catalyst system were
optimized. Ten reaction parameters in a single apparatus were
simultaneously examined under identical temperature and oxygen
pressure (balloon pressure).12,13 During each screen, aliquots were
periodically analyzed using an autosampling GC equipped with
a chiral column. The optimization procedure allowed us to
efficiently examine the effect of solvent, component concentration,
Pd(II) source, and molecular sieves14 on krel and reaction rate.
After screening these parameters, two sets of conditions were
identified. Conditions A: 0.5 M 1a in 1,2-dichloroethane,15 20
mol % (-)-sparteine, and 5 mol % of Pd(OAc)2 and conditions
B: 0.25 M 1a in 1,2-dichloroethane, 20 mol % (-)-sparteine,
and 5 mol % of a soluble PdCl2 source (Pd(MeCN)2Cl2 and Pd-
(COD)Cl2 gave similar results). Using both conditions the effect
of temperature was evaluated. For Pd(OAc)2, the temperature was
found to have a significant influence on enantioselectivity wherein
a temperature of 60 °C gave the highest krel value, while no
significant temperature effect was observed for PdCl2 sources.
Overall for 1a, the initial conditions were optimized from a krel
of 2.6 to 17.5 using conditions B.
(1) Barton, D. H. R.; Martell, A. E.; Sawyer, D. T. The ActiVation of
Dioxygen and Homogeneous Catalytic Oxidation; Plenum Press: New York,
1993.
(2) For a recent review, see: Sheldon, R. A.; Arends, I. W. C. E.; Dijksman,
A.Catal. Today 2000, 57, 157.
(3) Recent examples: (a) Ten Brink, G.-J.; Arends, I. W. C. E.; Sheldon,
R. A. Science 2000, 287, 1636. (b) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura,
S. J. Org. Chem. 1999, 64, 6750. (c) Nishimura, T.; Onoue, T.; Ohe, K.;
Uemura, S. Tetrahedron Lett. 1998, 39, 6011. (d) Peterson, K. P.; Larock, R.
C. J. Org. Chem. 1998, 63, 3185. (e) Marko´, I. E.; Giles, P. G.; Tsukazaki,
M.; Brown, S. M.; Urch, C. J. Science 1996, 274, 2044.
(4) Asymmetric dihydroxylation has been accomplished using O2, see: (a)
Wirth, T. Angew. Chem., Int. Ed. 2000, 39, 334. (b) Do¨bler, C.; Mehltretter,
G.; Beller, M. Angew. Chem., Int. Ed. 1999, 38, 3026.
(5) For a review of practical issues in kinetic resolutions, see: Keith, J.
M.; Larrow, J. F.; Jacobsen, E. N. AdV. Synth. Catal. 2001, 343, 5.
(6) Catalytic acylation: (a) Vedejs, E.; MacKay, J. A. Org. Lett. 2001, 3,
535. (b) Bellemine-Laponnaz, S.; Tweddell, J.; Ruble, J. C.; Breitling, F. M.;
Fu, G. C. Chem. Commun. 2000, 1009. (c) Jarvo, E. R.; Copeland, G. T.;
Papaioannou, N.; Bonitatebus, P. J., Jr.; Miller, S. J. J. Am. Chem. Soc. 1999,
121, 11638. (d) Vedejs, E.; Daugulis, O. J. Am. Chem. Soc. 1999, 121, 5813.
(e) Sano, T.; Imai, K.; Ohashi, K.; Oriyama, T. Chem. Lett. 1999, 265. (f)
Miller, S. J.; Copeland, G. T.; Papaioannou, N.; Horstmann, T. E.; Ruel, E.
M. J. Am. Chem. Soc. 1998, 120, 1629. (g) Ruble, J. C.; Tweddell, J. Fu, G.
C. J. Org. Chem. 1998, 63, 2794. (h) Ruble, J. C.; Latham, H. A.; Fu. G. C.
J. Am. Chem. Soc. 1997, 119, 1492. (i) Kawabata, T.; Nagato, M.; Takasu,
K.; Fuji, K. J. Am. Chem. Soc. 1997, 119, 3169.
(7) Recent oxidative approaches: (a) Masutani, K.; Uchida, T.; Irie, R.;
Katsuki, T. Tetrahedron Lett. 2000, 41, 5119. (b) Nishibayashi, I.; Takei, I.;
Uemura, S.; Hidai, M. Organometallics 1999, 18, 2291. (c) Gross, Z.; Ini, S.
Org. Lett. 1999, 1, 2077 (d) Hashiguchi, S.; Fujii, A.; Haack, K.-J.; Matsumura,
K.; Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed. Engl. 1997, 36, 288. (e)
Rychnovsky, S. D.; McLernon, T. L.; Rajapakse, H. J. Org. Chem. 1996, 61,
1194.
Next, the substrate scope of the oxidative kinetic resolution
was evaluated (Table 2). Using both conditions, benzylic second-
ary alcohols are generally good substrates for oxidative kinetic
resolution with krel values ranging from 8.7 to 23.6. Using Pd-
(11) krel ) ln[(1 - C)(1 - ee)]/ ln[(1 - C)(1 + ee)] where C is the
conversion and ee is the enantiomeric excess. For an excellent discussion of
kinetic resolutions, see: Kagan, H. B.; Fiaud, J. C. Kinetic Resolution. Top.
Stereochem. 1988, 18, 249.
(12) CAUTION: Organic solvents are highly flammable under O2.
(13) See Supporting Information for details.
(14) Molecular sieves have been used as a catalyst to disproportionate H2O2
formed in the reaction. See ref 3b.
(15) In the absence of O2, catalytic oxidation is not observed. DCE has
been used as a terminal oxidant in Pd(II)-catalyzed alcohol oxidations. For a
leading reference, see: A¨ıt-Mohand, S.; He´nin, F.; Muzart, J. Tetrahedron.
Lett. 1995, 36, 2473.
(8) Epoxidation: Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada, Y.;
Ikeda, M.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103, 6237.
(9) For examples of nonenzymatic desymmetrization of meso-diols via
acylation see: (a) Yamada, S.; Katsumata, H. J. Org. Chem. 1999, 64, 9365.
(b) Oriyama, T.; Imai, K.; Hosoya, T.; Sano, T. Tetrahedron Lett. 1998, 39,
397. (c) Via acetal cleavage, see: Fujioka, H.; Nagatomi, Y.; Kotoku, N.;
Kitagawa, H.; K. Tetrahedron 2000, 56, 10141. (d) Kinugasa, M.; Harada,
T.; Oku, A. J. Am. Chem. Soc. 1997, 119, 9067.
(10) Berrisford, D. J.; Bolm, C.; Sharpless, K. B. Angew. Chem., Int. Ed..
Engl. 1995, 34, 1059.
10.1021/ja015827n CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/07/2001

7476 J. Am. Chem. Soc., Vol. 123, No. 30, 2001
Table 2. Substrate Scope
Communications to the Editor
substituent
% conv
R
averaged
krel
entry
R1 conditionsa (% ee)b,c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1a C6H5
1b C6H5
Me
A
B
A
B
A
B
A
A
A
B
A
B
A
A
A
A
B
B
65.9(98.2)
53.9(86.9)
59.4(82.0)
57.5(88.5)
67.2(99.0)
72.1(99.0)
60.8(96.6)
57.0(94.3)
59.4(83.2)
48.6(70.3)
63.6(92.7)
47.5(71.5)
66.7(98.4)
52.9(80.7)
65.7(95.9)
58.5(77.8)
48.2(66.3)
43.5(66.1)
13.0
17.5
8.7
11.6
15.1
10.0
14.0
17.1
9.1
12.5
9.6
15.9
12.9
12.2
10.1
7.6
Figure 1. X-ray analysis of Pd(Cl)2/(-)-sparteine complex 4.
Et
To investigate the nature of the catalyst structure, an orange
single-crystal of the (-)-sparteine/PdCl2 complex, was obtained.
X-ray analysis of 4 showed the (-)-sparteine bound bidentate to
one side of a slightly distorted square plane of Pd (Figure 1).16
Additionally, the Pd-N bonds are slightly asymmetric with a
difference of 0.05 Å. Complex 4 was evaluated as a catalyst in
the oxidative kinetic resolution of 1a at 5 mol % and found to be
catalytically incompetent (eq 4). However, addition of (-)-
sparteine (10 mol %) reestablished normal catalytic activity and
enantioselectivity (eq 5), suggesting an exogenous base is
necessary for oxidation.
1c p-MeOC6H4 Me
1d p-MeC6H4
1e p-CF3C6H4
1f m-CF3C6H4
Me
Me
Me
1g m-MeOC6H4 Me
1h p-FC6H4
1i 2-Naphthyl
Me
Me
Me
16e 1j tert-Bu
17
18
1k o-MeOC6H4 Me
1l p-BrC6H4 Me
14.0
23.6
a Conditions A, Pd(OAc)2 at 60 °C and 0.5 M in substrate, Condition
B, Pd(MeCN)2Cl2 at 70 °C and 0.25 M in substrate. b Enantioselectivity
and conversion were determined by GC using commercial chiral
columns and tetradecane as an internal standard. c Data represents a
single experiment. d The krel value is an average of multiple experiments
and measured at 24 h. e At 80 °C.
In conclusion, a convenient method for enantioselective aerobic
alcohol oxidation has been discovered using a (-)-sparteine/Pd-
(II) catalyst. All reagents are commercially available and are used
without extensive purification. Benzylic alcohols give moderate
to good krel values in an oxidative kinetic resolution, and a meso-
1,3-diol is a good substrate for oxidative desymmetrization. The
application of enantioselective oxidations to other substrate types,
the identification of second-generation catalysts with antipodal
selectivity, and understanding of the origin of enantioselectivity
are currently being investigated.
(OAc)2, it can be seen that substituents on the aromatic ring
influence enantioselectivity with electron-rich alcohols giving
higher krel values than electron-poor substrates. However, no such
correlation is observed using PdCl2 sources. By increasing the
size of R1 from methyl to ethyl, a decrease in the krel is observed.
Using 1.0 g of the p-methyl substrate, 1d, in an oxidative kinetic
resolution, Pd(COD)Cl2 was the most effective Pd(II) source
giving the resolved alcohol in an isolated yield of 41.9% at 92.0%
ee with a slightly retarded rate. Resolution of an aliphatic alcohol
was also possible with a krel of 7.6 at 80 °C (entry 10). Overall,
the PdCl2-derived catalyst proved to be the most effective in terms
of krel values.
Acknowledgment. We thank University of Utah Research Foundation,
Merck Research, Rohm and Haas Research, and Invenux Inc. for support
of this research. This research was also supported by a Research
Innovation Award sponsored by Research Corporation. We acknowledge
Professor Fred West and Professor Brian Stoltz for helpful discussions.
The crystal structure analysis was performed by Atta Arriff.
Supporting Information Available: Experimental procedures and
characterization data are provided (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
An oxidative desymmetrization of a 1,3-meso-diol was also
investigated (eq 3). Treating the 1,3-diol 2 to Pd(MeCN)2Cl2/
(-)-sparteine conditions resulted in enantioselective oxidation
providing 3 in 82% ee and 69% yield (93% ee, 59% yield
recrystallized). Further oxidation of 3 to the diketone proved
exceedingly slow.
JA015827N
(16) For Pd(II)/(-)-sparteine π-allyl complexes, see: (a) Trost, B. M.;
Dietsche, T. J. Am. Chem. Soc. 1973, 95, 8200. (b) Togni, A. Tetrahedron:
Asymmetry 1991, 2, 683.