New palladium(II)-catalyzed asymmetric 1,2-dibromo synthesis

Article abstract of DOI:10.1021/ol0273093

(Matrix presented) The oxidation of olefins by chiral monometallic and bimetallic Pd(II)-Cu(II) catalysts in bromide-containing aqueous-THF reaction mixtures produced chiral 1,2-dibromides. With α-olefins, the ee's were about 95% while most of the interna

Full text of DOI:10.1021/ol0273093

ORGANIC
LETTERS
2
003
Vol. 5, No. 4
39-441
New Palladium(II)-Catalyzed Asymmetric
,2-Dibromo Synthesis
Arab K. El-Qisairi, Hanan A. Qaseer, George Katsigras, Philip Lorenzi,
Unnati Trivedi, Sylvia Tracz, Amy Hartman, Jason A. Miller, and
Patrick M. Henry*
4
1
†
†
Department of Chemistry, Loyola UniVersity of Chicago, Chicago, Illinois 60626
phenry@luc.edu
Received November 19, 2002
ABSTRACT
The oxidation of olefins by chiral monometallic and bimetallic Pd(II)−Cu(II) catalysts in bromide-containing aqueous−THF reaction mixtures
produced chiral 1,2-dibromides. With r-olefins, the ee’s were about 95% while most of the internal alkenes gave somewhat lower
enantioselectivities (∼80%).
In some reactions of 1,2-dibromides, elimination of HBr
1
occurs with or without substitution, there are many reactions
Scheme 1. Reaction of Ethene under Two Sets of [Cl-] and
2
where substitution takes place without elimination. With
chiral 1,2-dibromides, these latter systems could be the basis
of new asymmetric syntheses. Yet the use of chiral 1,2-
dibromides in asymmetric synthesis is very limited because
there are no simple means of preparing these starting
materials. Thus, the development of a convenient one-step
synthesis of chiral 1,2-dibromides would provide a valuable
new tool for asymmetric synthesis.
[CuCl ] Conditions
2
Previous papers from these laboratories described a
3
palladium(II)-catalyzed asymmetric chlorohydrin synthesis.
(
Figure 1), asymmetric induction occurs to give chiral
Although Pd(II) salts in aqueous solution oxidize ethene to
-
chlorohydrins (Scheme 2). In general, the bimetallic catalysts
B provided the highest enantioselectivities. In some cases,
the ee’s were >90%. The 1/2 ratios ranged from 2.5 to 12
acetaldehyde under the usual Wacker conditions ([Cl ] ∼1
-
M; [CuCl
(
1
2
] ∼1 M), at higher [Cl ] (>2 M) and [CuCl
2
]
>2.5 M), chlorohydrins become the main product (Scheme
).
If monometallic or bimetallic catalytic species containing
chiral chelating diphosphine or diamine ligands are employed
†
Present address: Department of Chemistry, Mu’tah University, P. O.
Box 7, Mu’tah - Karak, Jordan.
(
1) (a) Kashima, C.; Tajima, T.; Omote, Y., J. Heterocycl. Chem. 1984,
2
1
1, 171. (b) Hagiwara, H.; Abe, F.; Uda, H. J. Chem. Soc., Perkin Trans.
1993, 2651. (c) Fevig, J. M.; Marquis, R. W.; Overman, L. E. J. Am.
Chem. Soc. 1991, 113, 5085.
2) (a) Brunner, O. Monatsh. Chem. 1954, 85, 915. (b) Ley, S. V.;
Middleton B. Chem. Commun. 1998, 1995. (c) Mishra, A.; Dash, B. L.;
Behera, R. K. Indian J. Heterocycl. Chem. 1996, 6, 149.
(
Figure 1. Structures of monometallic and bimetallic catalysts.
1
0.1021/ol0273093 CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/30/2003

Table 1. Results for the Oxidation of Several Substratesa
entry
L*-L*b
catalyst
[LiBr] (M)
substrate
% yield of 3
% ee of 3
catalyst turnovers
1
2
3
4
5
6
7
8
9
(S)-BINAP
(S)-Tol-BINAP
(S)-BINAP
(S)-BINAP
(S)-METBOX
(S)-BZOX
(S)-METBOX
(R)-BINDA
(R)-BINDA
(R)-BINDA
B
B
B
A
B
A
B
B
B
B
0.25
0.13
0.20
0.20
0.20
0.30
0.30
0.20
0.0
p-CH3O-phenyl allyl ether
p-CN-phenyl allyl ether
phenyl allyl ether
(2,6-diisopropyl)phenyl allyl ether
methyl acrylate
methyl crotonate
methyl crotonate
cinnamyl alcohol
cinnamyl alcohol
95
95
95
95
84
80
80
77
75
84
96
97
95
94
85
88
148
80
25
13
30
21
20
10
94
84c
82c
80c
34c
14c
1
0
0.20
methyl trans-cinnamate
a
All runs contain 0.05-0.12 mmol of chiral catalyst in 20-30 mL of solvent and 2.0-2.5 M in CuBr2. Temperature ) 25 °C. The solvent was a
b
H2O/THF mixture containing 54-93% THF by volume. (S)-BINAP ) (S)-(-)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, (S)-Tol-BINAP ) (S)-(-)-
2
2
,2′-bis(ditolylphosphino)-1,1′-binaphthyl, (S)-METBOX ) 2,2′-methylenebis[(4S)-4-tert-butyl-2-oxazoline], (S)-BZOX ) 2,2′-methylenebis[(4S)-4-benzyl-
-oxazoline], (R)-BINDA ) (R)-(+)-1,1′-binaphthyl-2,2′-diamine. c These dibromides have the (RS,SR) configuration.
for simple R-olefins but were >90 for allyl ethers. Aldehydes
and ketones constituted 5-20% of the total product.
Table 1 ranged from 10 to 150, but the rate did not decrease
during the course of the reaction. This raises the possibility
that catalyst turnovers could be further increased, though we
have yet to demonstrate this experimentally.
The first three runs with para-substituted phenyl allyl ethers
test the electronic effects on the oxidation. Since the results
for all three runs were very similar, electonic effects have
little impact on enantioselectivity in this series of substrates.
This result is consistent with other palladium(II) catalytic
2
Scheme 2. CuCl -Promoted Chlorohydrin Synthesis
4
chemistry. Entry 4 suggests that steric hindrance is not an
important factor.
The enantioselectivities for the internal olefins were
somewhat poorer than those found for the R-olefins. This
could not be due to the variation in chiral ligand. Entries 5
and 6 have the same ligand, but the % ee decreased from 94
for oxidation of methyl acrylate to 82 for the oxidation of
methyl crotonate. In addition, the rates, catalyst turnovers,
and yields were poorer for the runs with internal alkenes.
Entries 8 and 9 demonstrate the important of bromide ion
concentration. When no extra bromide is added, the ee drops
from 34% from 80%. The low enantioselectivity observed
with methyl trans-cinnamate is surprising, but similar re-
sults were observed for several other runs using this sub-
strate.
This paper reports the results obtained for the reaction in
bromide-containing media. Surprising, the oxidation of
olefins did not produce the expected bromohydrin. Instead,
the predominate products were the 1,2-dibromides (Scheme
3). Furthermore, for R-olefins, the dibromides were obtained
Scheme 3 Dibromo Synthesis
These results can be compared with those for the chloro-
hydrin reaction where internal olefins were completely
unreactive. In addition, with R-olefins, a certain minimal
-
concentration of [Cl ] had to be present to achieve the
maximum enantioselectivities. The dibromo product, 3, from
methyl crotonate, cinnamyl alcohol, and methyl trans-
cinnamate has the (RS,SR) configuration. This result is
consistent with trans addition to the double bond. To establish
the stereochemistry of the reaction further a sample of
cyclopentene was reacted under the conditions used in Table
in high enantioselectivity (ee ∼95%). Both monometallic,
A, and bimetallic, B, catalysts were effective. Table 1 lists
the results for several olefins.
As with the chlorohydrin synthesis, the reaction is a net
air oxidation since the CuBr formed in the dibromo reaction
1
. The main product was the expected 1,2- dibromocyclo-
2
is oxidized back to CuBr by oxygen. Catalyst turnovers in
pentane in 85% yield. The dibromocyclopentane had the trans
configuration. As shown in Scheme 4, using catalyst A for
simplicity, the stereochemistry is consistent with anti attack
(
3) (a) El-Qisairi, A.; Hamed, O.; Henry, P. M. J. Org. Chem. 1998, 63,
2
5
6
790-2791. (b) Hamed, O.; Henry, P. M. Organometallics 1998, 17, 7,
184-5189. (c) El-Qisairi, A.; Henry, P. M. J. Organomet. Chem. 2000,
03, 50-60. (d) El-Qisiari, A. K.; Qaseer, H. A.; Henry, P. M. J.
(4) Henry, P. M. Palladium Catalyzed Oxidation of Hydrocarbons; D.
Reidel: Dordrecht, Holland, 1980; pp 73-74.
Organomet. Chem. 2002, 656/1-2, 167-175.
440
Org. Lett., Vol. 5, No. 4, 2003

The fact that the bromide system produces dibromides
rather than bromohydrins almost exclusively can be attributed
to the strength of bromide as a nucleophile. The bromide
must be a much better nucleophile than chloride or water in
palladium(II) catalytic chemistry since, for the examples in
Table 1, the concentration of water is at least 200 times the
concentration of bromide.
Scheme 4. Reaction Pathway for the Oxidation of
Cyclopentene
Acknowledgment. This work was supported by the
Petroleum Research Fund, administered by the American
Chemical Society, and the National Science Foundation
(CHE-9727526) We are also grateful for Research Experi-
ence for Undergraduates summer fellowships for G.K., A.H.,
and J.M. (CHE-9619709).
of bromide followed by decomposition involving attack of
bromide from the coordination sphere of the Pd(II). It is also
possible that the bromide comes from the Cu(II) coordinated
to the Pd(II). A similar scheme was postulated for the
Supporting Information Available: Procedures and
spectra data for chiral syntheses. This material is available
free of charge via the Internet at http://pubs.acs.org.
3
b
chlorohydrin product in the chlorine-containing system.
OL0273093
Org. Lett., Vol. 5, No. 4, 2003
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