Vaulted biaryls: Efficient ligands for the aluminum-catalyzed asymmetric baeyer-villiger reaction

Article abstract of DOI:10.1055/s-2004-829080

Vaulted biaryls (VANOL and VAPOL) have been applied in the aluminum-catalyzed asymmetric Baeyer-Villiger reaction of prochiral 3-substituted cyclobutanones. Optically active γ-butyrolactones are obtained in high yields with enantioselectivities of up to 84% ee.

Full text of DOI:10.1055/s-2004-829080

LETTER
1619
Vaulted Biaryls: Efficient Ligands for the Aluminum-Catalyzed Asymmetric
Baeyer–Villiger Reaction
a
a
b
b
L
C
igands for the
A
a
luminum-C
r
atalyzed
s
A
symme
t
tric Ba
e
eyer–Villig
n
er Reaction Bolm,* Jean-Cédric Frison, Yu Zhang, William D. Wulff
a
Institut für Organische Chemie der RWTH Aachen, Professor Pirlet-Str. 1, 52056 Aachen, Germany
Fax +49(241)8092391; E-mail: Carsten.Bolm@oc.RWTH-Aachen.de
b
Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA
Received 20 March 2004
Abstract: Vaulted biaryls (VANOL and VAPOL) have been ap-
plied in the aluminum-catalyzed asymmetric Baeyer–Villiger
reaction of prochiral 3-substituted cyclobutanones. Optically active
g-butyrolactones are obtained in high yields with enantioselectivi-
ties of up to 84% ee.
Ph
Ph
OH
OH
Ph
Ph
OH
OH
OH
OH
Key words: aluminium, asymmetric catalysis, Baeyer–Villiger
reaction, biaryls, lactones
1
2
3
The Baeyer–Villiger reaction is a synthetically highly
useful oxidative rearrangement of ketones into lactones or
O
1
O
esters. Recently, much effort has been devoted to the
Me2AlCl, ligand
CHP, toluene, –15 °C
search of metal-catalyzed variants of this transformation.2
Although several metals were found to promote the reac-
O
2
tion, only very few of them proved useful for the devel-
opment of asymmetric variants. To date, the application of
chiral Lewis acids represents the most successful ap-
proach allowing the conversion of prochiral (or racemic)
4
5
3
Scheme 1
cycloalkanones into enantioenriched lactones.
We recently reported that the use of dialkylaluminum re-
agents in combination with enantiopure BINOL catalyzed
the reaction of prochiral cyclobutanones yielding the cor-
responding lactones in high yields and enantioselectivities
In order to ensure that the vaulted biaryls were also appli-
cable in asymmetric Baeyer–Villiger reactions, a test sys-
tem with 3-phenylcyclobutanone (4) as substrate,
dimethylaluminum chloride as metal source and either
VANOL (1), VAPOL (2), or BINOL (3) as ligand was es-
tablished (Scheme 1). Using cumene hydroperoxide
(CHP, 1.2 equiv) as oxidant and 20 mol% of a 1:1 mixture
4
up to 77% ee. With the goal to find aluminum-based cat-
alysts with improved properties, we screened the use of
several chiral biphenol derivatives, whose syntheses are
5
well-documented in the literature. While 6,6¢-disubstitut-
of Me AlCl and the ligand in toluene at –15 °C lactone 5
2
ed BINOLs provided more efficient catalysts, both the ac-
tivity and the enantioselectivity of the resulting catalysts
were dramatically reduced, when 3,3¢-disubstituted
was obtained selectively in all three cases. The R-config-
ured ligand led to the formation of the R enantiomer of the
product in all three cases. The enantioselectivity, howev-
er, differed significantly. Whereas use of VANOL gave 5
with 80% ee reactions with VAPOL and BINOL afforded
the lactone with only 14% and 68% ee, respectively. Ap-
parently, the catalyst bearing the vaulted biaryl VANOL
was superior over the one prepared from BINOL. The fact
that the VANOL-based system gave a higher enantiose-
lectivity than its VAPOL counterpart was expected and in
good agreement with our previous observations, since it
was found that increased steric bulk at the 3,3¢-positions
of the biaryl led to a reduced enantioselectivity. In all
three Baeyer–Villiger reactions the absolute configuration
of the major enantiomer of the product was identical.
4
BINOLs were applied as ligands. Beside these linear bi-
aryls, we decided to test the vaulted derivatives VANOL
(
1) and VAPOL (2), which had been introduced by Wulff
6
7
and co-workers. Both compounds are readily available
and have successfully been applied as ligands in various
8
asymmetric catalyses including aziridinations, Mannich
9
6
type reactions, and cycloadditions. In all of those catal-
yses, the use of VANOL and VAPOL provided more effi-
cient catalysts than BINOL leading to better activities and
improved enantioselectivities.
The promising result with the catalyst obtained from 1
prompted us to investigate this particular system in more
detail. Assuming that the enantioselectivity increased in
catalyses at lower temperatures, the Baeyer–Villiger
SYNLETT 2004, No. 9, pp 1619–1621
Advanced online publication: 29.06.2004
DOI: 10.1055/s-2004-829080; Art ID: G08704ST
2
2.
0
7.
2
0
0
4
©
Georg Thieme Verlag Stuttgart · New York

1
620
C. Bolm et al.
LETTER
reaction with 4 was performed at –30 °C. Gratifyingly, the Table 2 Substrate Scope of the Asymmetric Baeyer–Villiger Reac-
tion Catalyzed by Mixtures of Me AlCl and VANOL (1)
ee of the corresponding lactone was now raised to 83% ee,
and 5 was obtained in 91% yield after column chromato-
graphy. Attempts to further increase the enantioselectivity
by reducing the temperature remained unsuccessful.
Thus, below –30 °C the reaction became rather slow, and
even after prolonged reaction times it did not go to com-
pletion. Furthermore, the ee of the product remained Entry
2
O
Me2AlCl, VANOL (1)
(20 mol% each)
O
O
CHP (1.2 equiv),
toluene, –30 °C
R
R
6
7
R
Substrate Yield (%) ee (%)
1
0
of 7a
b,c
unchanged.
of 7
Beside the temperature, the catalyst loading is known to
have a significant influence on the enantioselectivity of
the aluminum-catalyzed Baeyer–Villiger reaction. In the
original system using BINOL (3) as ligand, 50 mol% of
1
2
3
6a
6b
6c
92
84
Cl
84
96
41
34
Me AlCl and the ligand (in a 1:1 ratio) were required to
2
4
achieve enantioselectivities >70% ee. To our delight we
found that such high catalyst loading was not essential in
the VANOL-based system. Here, the Baeyer–Villiger
MeO
O
4
5
6d
6e
93
86
37
69
reaction of 4 with 20 mol% of Me AlCl/VANOL gave al-
2
most the same result as the one with 50 mol% of the cata-
lyst (83% versus 84% ee). In both cases full conversion of
the substrate was achieved, albeit the reaction was faster
when more catalyst was applied (Table 1, entries 1 and 2).
Reducing the catalyst loading to 10 mol% or even 5 mol%
led to incomplete conversion and lower ee values of 5.
O
n-octyl
a
b
c
As determined by NMR spectroscopy.
Determined by GC using a chiral column (Lipodex B).
Using (R)-VANOL as ligand, (–)-(R)-7a and (–)-7e (entries 1 and 5,
respectively) were obtained. The absolute configurations of products
b–d remained undetermined.
7
Table 1 Influence of the Catalyst Loading on the Asymmetric
Baeyer–Villiger Reaction of Cyclobutanone 4a
Entry
Catalyst (mol%)
Conversion (%)b
ee (%)c
84
VANOL-based catalyst was entirely unreactive towards 8
and that almost no conversion of the substrate occured
1
2
3
50
20
10
5
100d
100e
83
(
under the standard conditions described above). Even af-
83
ter 48 hours reaction time only traces of (the ‘normal’)
lactone 9 were formed, and the enantiomer ratio analysis
by HPLC using a chiral column revealed that the product
was racemic. In the light of the results obtained with the
BINOL/aluminum-system this observation is surprising,
since there 8 was readily converted into the ring-expanded
products 9 and 10 with the latter (‘abnormal’) lactone
being the major isomer formed with high ee. Presumably,
the difference between the two systems is caused by steric
hindrance of the ligand in the VANOL-based one, which
hampers the coordination of the bulky substrate to the
Lewis-acidic metal center. The lack of activation then
results in the observed uneffectiveness of the catalysis.
43
4
43
14
a
The reaction was performed at –30 °C in toluene (0.05 M in ketone).
Determined by GC.
Determined by GC using a chiral column (Lipodex B).
The reaction was complete after 4 h.
b
c
d
e
The reaction was complete after 12 h.
Next, the substrate scope was evaluated by using various
cyclobutanones as starting materials. Under the optimized
conditions (20 mol% of each Me AlCl and VANOL in
toluene at –30 °C and CHP as oxidant), 3-substituted de-
rivatives 6 afforded optically active lactones with up to
2
1
1
O
O
Baeyer-Villiger
reaction
O
O
+
O
8
4% ee. As shown in Table 2 (entry 1), 3-p-chlorophenyl-
cyclobutanone (6a) gave the corresponding lactone with
almost) the same ee (84%) as phenyl-substituted 4 (83%
8
9
10
(
ee). Cyclobutanones with benzylic substituents in the 3-
position led to lactones with enantiomeric excesses in the
range of 34–41% (entries 2–4). Alkyl-substituted deriv-
Scheme 2
1
2
In summary, vaulted biaryls have successfully been ap-
plied in the aluminum-catalyzed asymmetric Baeyer–Vil-
liger reactions of 3-substituted cyclobutanones.
Enantiomerically enriched lactones with up to 84% ee
were obtained. For catalyzed conversions of such simple
ative 6e afforded the product with remarkable 69% ee.
Besides achiral cyclobutanones, such as those listed in
Table 2, racemic (bicyclic) cyclobutanone derivatives
such as 8 are also known to undergo asymmetric Baeyer–
Villiger reactions giving optically active lactones
substrates these enantioselectivities are among the best
3
ever achieved.3
,4,13,14
Furthermore, compared to the
(
Scheme 2). To our surprise we found that the new
Synlett 2004, No. 9, 1619–1621 © Thieme Stuttgart · New York

LETTER
Ligands for the Aluminum-Catalyzed Asymmetric Baeyer–Villiger Reaction
1621
original BINOL-based system the catalyst loading for
achieving full ketone conversion could significanly be re-
duced from 50 mol% to only 20 mol% of catalyst. Our
current efforts are directed towards further catalyst opti-
mizations.
(7) Zhang, Y.; Yeung, S.-M.; Wu, H.; Heller, D. P.; Wu, C.;
Wulff, W. D. Org. Lett. 2003, 5, 1813.
(
(
8) (a) Loncaric, C.; Wulff, W. D. Org. Lett. 2001, 3, 3675.
(
b) Antilla, J. C.; Wulff, W. D. Angew. Chem. Int. Ed. 2000,
39, 4518. (c) Antilla, J. C.; Wulff, W. D. J. Am. Chem. Soc.
1999, 121, 5099.
9) Xue, S.; Yu, S.; Deng, Y.-H.; Wulff, W. D. Angew. Chem.
Int. Ed. 2001, 40, 2271.
Acknowledgment
(
(
10) After 72 h at –40 °C the reaction was quenched to give the
lactone with 84% ee in 40% yield.
11) Experimental Procedure for the Al-Catalyzed
Asymmetric Baeyer–Villiger Reaction.
The Deutsche Forschungsgemeinschaft within the Graduierten-
kolleg 440 and the Fonds der Chemischen Industrie are gratefully
acknowledged for financial support. This work was also supported
by the National Institutes of Health Grant GM 63019.
To a solution of (R)-VANOL (26.4 mg, 0.06 mmol) in
toluene (2.5 mL) was added dropwise Me AlCl (0.06 mmol,
2
60 mL, 1 M solution in hexanes) at r.t. The mixture was
References
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this temperature, a solution of the ketone (0.3 mmol) in
toluene (0.5 mL) was added. Stirring was continued for 15
min, cumene hydroperoxide (technical grade 80%, 1.2
equiv, 75 mL) was then added in one portion. Subsequently,
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(
1) (a) Krow, G. R. Org. React. 1993, 43, 251. (b) Krow, G. R.
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was then evaporated, and the crude product absorbed onto
silica gel. Extraction with Et O afforded the crude product,
2
which was analyzed by GC or HPLC using chiral columns
(
for details of the enantiomeric ratio determinations and
assignments of absolute configurations, see ref. 4 and
references therein).
(
3) Reviews: (a) Bolm, C.; Luong, T. K. K.; Beckmann, O. In
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(
(
12) Slightly better results can be obtained for benzyl-substituted
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2
system are applied (comp. ref. 4a). Thus, conversions of 6c
and 6d give lactones with 73% and 58% ee, respectively.
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3
48.
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(
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(
14) To the best of our knowledge there is only a single report
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conversion of 4 to 5. See: Watanabe, A.; Uchida, T.; Ito, K.;
Katsuki, T. Tetrahedron Lett. 2002, 43, 4481.
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(
1
Synlett 2004, No. 9, 1619–1621 © Thieme Stuttgart · New York