Highly enantioselective copper-bisoxazoline-catalyzed allylic oxidation of cyclic olefins with tert-butyl p-nitroperbenzoate

Article abstract of DOI:10.1021/ja026266i

Catalytic asymmetric allylic oxidation of cyclic olefins ocurrs for the first time in very high (94-99% ee) enantioselectivity using copper(I) complexes of malonyl derived bisoxazolines and tert-butyl p-nitroperbenzoate giving allyl benzoates in moderate

Full text of DOI:10.1021/ja026266i

Published on Web 06/29/2002
Highly Enantioselective Copper-Bisoxazoline-Catalyzed Allylic Oxidation of
Cyclic Olefins with tert-Butyl p-nitroperbenzoate
Merritt B. Andrus* and Ziniu Zhou
Brigham Young UniVersity, Department of Chemistry and Biochemistry, C100 BNSN, ProVo, Utah 84602-5700
Received March 21, 2002
Table 1. Asymmetric Allylic Oxidation of Cyclohexene
While a range of ligands have been explored, copper-catalyzed
allylic oxidation with peresters1 has been hampered by poor
reactivity and selectivity. We now report a highly selective process
using a panel of eight malonyl-derived bisoxazolines together with
tert-butyl p-nitroperbenzoate to provide enantiomerically enriched
ester products with cyclic olefins. Asymmetric versions2 have been
explored using camphorate esters and catalytic amino acid copper
complexes at lower temperatures with varying results.3 Enantio-
selectivities improved to 80% ee using di-tert-butyl and phenyl-
bisoxazolines with tert-butyl perbenzoate.4
A number of bisoxazoline and trioxazoline ligands have been
explored since that time that give, in the case of cyclopentene, high
selectivity.5 Pyridyl and bipyridyl bisoxazoline ligands with added
phenylhydrazine in acetone show improved reactivity but again with
only modest 80% ee selectivity at best.6 Biaryl and aminoindanol
ligands have also been explored with limited success.7 We now
report the results from a panel of eight malonyl-derived bisoxazoline
complexes as catalysts reacted with p-nitroperbenzoate8 with cyclic
olefins. Unique ligand-substrate combinations are identified to now
give excellent selectivities for the first time, 94-99% ee, for ester
products. These selectivities now compliment catalytic epoxidation
and dihydroxylation methods that occur with high selectivity.9
Allylic oxidation offers the unique advantage of maintaining the
alkene functionality in the allylic ester product. This utility is seen
in the conversion of cyclohexenyl benzoate to the key intermediate
in the synthesis of leukotriene B4.10
c
entry
R
R′
time (d)a
% yieldb
ee
1
2
3
4
5
5
6
7
8
t-Bu
-
Me
Me
Me
Me
Me
Et
7
21
17
6
61
43
44
30
40
25
50
50
26
84
80d
96
71
82
16
75
53
78
Ph
Bn
i-Pr
t-Bu
Ph
6
16
13
12
5
Et
Bn
i-Pr
Et
Et
a Time in days, using a sealed vial placed in the freezer with stirring.
b Yields are for isolated, chromatographed materials based on the perester.
c Enantiomeric excesses were determined by chiral normal phase HPLC.
d Unsubstituted perester. tert-Butyl perbenzoate used.
Table 2. Oxidation of Cyclopentene
c
time (d)a
% yieldb
ee
Eight malonyl gem-dimethyl and gem-diethyl bisoxazolines11
were used for this study together with tert-butyl p-nitroperbenzoate,
mp 75 °C, made from anhydrous tert-butyl hydrogen peroxide and
p-nitrobenzoyl chloride.12 The reactions were performed by forming
the copper(I) hexafluorophosphate13-bisoxazoline complex (15 mol
%) in degassed acetonitrile (0.2 M) at room temperature and adding
5 equiv of olefin followed by perester (1 equiv) at -20 °C (Table
1). The reactions were monitored by TLC for consumption of
perester and stopped at the given time. The yields are for isolated
materials based on the perester, and the selectivities were determined
by chiral HPLC with comparison to racemic compound. Yields were
moderate for the purified ester products; however, the ligands could
be recovered in 85% yield based on the amount used and recycled.
In all cases the S,S ligands generated (S)-ester product.14 The
cyclohexenyl ester was obtained with very high 96% ee selectivity
using the diphenyl gem-dimethyl bisoxazoline (entry 3). The gem-
diethyl ligands showed lower reactivity and selectivity. Interestingly,
in the case of entry 3, when the reaction was monitored every 48
h, a gradual increase in both yield and selectivity was noted.15 The
possibility of product resolution was explored in this case by treating
racemic ester product with the ligand-copper(I) complex, perester,
and tert-butyl alcohol in CH3CN. After 11 days at -20 °C, the
entry
R
R′
1
2
3
4
5
6
7
8
t-Bu
Ph
Me
Me
Me
Me
Et
10
10
10
10
10
8
52
49
25
42
31
41
28
36
79
82
75
51
38
99
80
83
Bn
i-Pr
t-Bu
Ph
Bn
i-Pr
Et
Et
Et
8
8
a Time in days, using a sealed vial placed in the freezer with stirring.
b Yields are for isolated, chromatographed materials based on the perester.
c Enantiomeric excesses were determined by chiral normal phase HPLC.
ester remained racemic. In contrast, 58% ee enriched ester product
exposed to the reaction conditions for 17 days gave product in 85%
yield enriched to 84% ee.
The oxidation of cyclopentene using gem-dimethyl ligands
showed moderate to good selectivity, 51-82% ee (Table 2). In
contrast, the use of the gem-diethyl set identified a highly selective
catalyst, the diphenyl complex that gave product with remarkable
99% ee selectivity. In this case, both the di-Bn and di-i-Pr ligands
were moderately selective (entries 7, 8), while the more sterically
congested di-tert-butyl ligand gave poor selectivity (entry 5, 38%
ee).
The panel of eight ligands was also applied to the asymmetric
oxidation of the less reactive substrates cycloheptene and 1,5-
* Address for correspondence. Telephone: (801) 422-8171. E-mail: mbandrus@
chemdept.byu.edu.
9
8806
J. AM. CHEM. SOC. 2002, 124, 8806-8807
10.1021/ja026266i CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 3. Oxidation of Cycloheptene
Scheme 1
entry
R
R′
% yielda
eeb
1
2
3
4
t-Bu
ph
i-Pr
Ph
Me
Me
Me
Et
3
23
14
12
95
56
99
86
a Yields are for isolated, chromatographed materials based on the perester.
b Enantiomeric excesses were determined by chiral normal phase HPLC.
Table 4. Asymmetric Oxidation of COD
entry
R
R′
% yielda
eeb
1
2
3
4
5
t-Bu
Ph
i-Pr
Ph
i-Pr
Me
Me
Me
Et
13
46
25
34
27
94
74
36
59
78
Et
further explore the factors that contribute to the selectivity and
catalyst activity.
a Yields are for isolated, chromatographed materials based on the perester.
b Enantiomeric excesses were determined by chiral normal phase HPLC.
Acknowledgment. We are grateful for the support provided by
the National Science Foundation (Career Award to M.B.A., CHE-
9501867) and Brigham Young University.
cyclooctadiene. The results shown again indicate that very high
selectivity can be obtained via a unique ligand combination. The
gem-dimethyl di-i-Pr ligand (entry 3, Table 3) proved best at 99%
ee for cycloheptene. In this case the reactivity was very poor at
14% yield, indicating only a single turnover of the catalyst. In
general cycloheptene has shown lower reactivity and selectivity
compared to cyclopentene and cyclohexene.6,7 The di-tert-butyl
ligand, while highly selective at 95% ee, again showed low
reactivity. The gem-diethyl set was also low, yet the diphenyl ligand
in this case showed good selectivity at 86% ee (entry 4).
Cyclooctadiene was oxidized in high 94% ee selectivity using the
gem-dimethyl di-tert-butyl copper catalyst (entry 1, Table 4). Higher
yields were found with other ligands in this case, but the selectivities
were lower.
Supporting Information Available: Experimental procedures,
characterization, and HPLC data (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
References
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10-mm, low-temperature 13C NMR (75 MHz, -35 °C) in CD3CN
at 1:1 stoichiometry. Shifts for the complex are shown, indicating
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(Scheme 1). The gem-diethyl di-tert-butyl ligand was selected due
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anticipated with the copper complex in this case. When cyclohexene
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intermediate. Indeed when CuPF6 is complexed alone with cyclo-
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an η2 interaction.16 Yet upon addition of bisoxazoline, only free
olefin was observed. The copper chelate is clearly favored, while
a ligand-copper-cycloalkene complex is not. The selectivity then
is most likely a consequence of the allylic radical approach to the
copper(II) benzoate complex. Attack of the less hindered quadrant
of the C2-copper complex gives the copper(III) intermediate
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S-ester product and copper(I) complex.
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(12) See Supporting Information for full details.
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(14) Levorotatory allyl alcohols were produced upon hydrolysis (KOH) of the
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(15) Aliquots from the reaction showed on day 3 41% yield (70% ee), day 7
42% yield (73% ee), day 11 45% yield (77% ee), day 13 54% yield (88%
ee), and days 15 and 17 55% yield (95% ee). See Supporting Information.
(16) Quan, R. W.; Li, Z.; Jacobsen, E. N. J. Am. Chem. Soc. 1996, 118, 8156-
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A panel of bisoxazoline ligands with tert-butyl p-nitroperbenzoate
identified unique ligand-substrate combinations that now give very
high enantioselectivities for asymmetric allylic oxidation. Efforts
are now underway to improve the reactivity of the process and
(17) Walling, C.; Zavitsas, A. A. J. Am. Chem. Soc. 1963, 85, 2084-2090.
Beckwith, A. L.; Zavitsas, A. A. J. Am. Chem. Soc. 1986, 108, 8230-8234.
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