Highly enantioselective Baeyer-Villiger oxidation using Zr(salen) complex as catalyst

Article abstract of DOI:10.1016/S0040-4039(02)00831-6

(R,R)-Zr(salen) complex was found to serve as an efficient catalyst for asymmetric Baeyer-Villiger oxidation of pro-chiral and racemic ketones using urea·hydrogen peroxide as the terminal oxidant: for example, high enantioselectivity of 87% ee was achieve

Full text of DOI:10.1016/S0040-4039(02)00831-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4481–4485
Highly enantioselective Baeyer–Villiger oxidation using Zr(salen)
complex as catalyst
Akira Watanabe,a Tatsuya Uchida,a Katsuji Itob and Tsutomu Katsukia,*
aDepartment of Chemistry, Faculty of Science, Graduate School, Kyushu University 33, CREST JST (Japan Science and
Technology), Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
bDepartment of Chemistry, Fukuoka University of Education, CREST JST, Akama, Munakata, Fukuoka 811-4192, Japan
Received 25 March 2002; accepted 26 April 2002
Abstract—(R,R)-Zr(salen) complex was found to serve as an efficient catalyst for asymmetric Baeyer–Villiger oxidation of
pro-chiral and racemic ketones using urea·hydrogen peroxide as the terminal oxidant: for example, high enantioselectivity of 87%
ee was achieved in the Baeyer–Villiger reaction of 3-phenylcyclobutanone. © 2002 Elsevier Science Ltd. All rights reserved.
The Baeyer–Villiger (B–V) reaction, oxidative conversion
of carbonyl to ester (or lactone), is of high synthetic value
and has been widely used in various syntheses. Although
many biocatalyzed asymmetric B–V reactions are
known,1 their chemical versions are still limited in
number. In 1994, Bolm et al. reported copper-catalyzed
asymmetric B–V reaction.2 In the same year, Strukul et
al. reported platinum-catalyzed asymmetric B–V reac-
tion.3 Since then, several catalysts have been introduced
for asymmetric B–V reaction4 and high enantioselectivity
has been realized in the B–V reactions of some limited
substrates.5 Still, introduction of new methodology for
asymmetric B–V oxidation is strongly required.
B–V oxidation is a two-step reaction: (i) nucleophilic
addition of an oxidant giving the Criegee adduct and (ii)
rearrangement of the adduct to ester (or lactone). If the
starting carbonyl compound is a pro-chiral cyclic one, the
B–V oxidation product is a pair of enantiomeric lactones
(Scheme 1). The stereochemistry of the B–V reaction is
dictated by two factors: face selectivity in oxidant addi-
tion and enantiotopos selectivity in migration. However,
as Criegee adduct formation is a reversible step and its
migration to lactone is an irreversible and rate-determin-
ing one, topos-selection in the migration step is consid-
ered to strongly influence the stereochemistry of B–V
reaction.
Scheme 1.
Keywords: Zr(salen) complex; asymmetric catalysis; Baeyer–Villiger oxidation; hydrogen peroxide.
* Corresponding author. Fax: +81-92-642-2607; e-mail: katsuscc@mbox.nc.kyushu-u.ac.jp
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00831-6

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A. Watanabe et al. / Tetrahedron Letters 43 (2002) 4481–4485
We recently reported highly enantioselective sulfoxida-
tion using di-m-oxo Ti(salen) of cis-b structure 3 as the
catalyst, which proceeded through a peroxy Ti(salen)
intermediate 4.7 We expected that complex 3 would also
serve as the catalyst for B–V reaction but it showed
little catalytic activity. The peroxy ring of 4 must be
opened to allow carbonyl coordination for B–V oxida-
tion (Scheme 3). Due to high oxophilicity of titanium
ion, however, the ring-opening was considered to be
slow. On the other hand, titanium and zirconium ions
have similarities in many respects, and we expected that
treatment of the Zr(salen) complex with hydrogen per-
oxide would give a peroxy Zr(salen) complex 5 of cis-b
structure.8 Due to the less oxygenophilic nature of the
zirconium ion and the longer ZrꢀO bond, however, a
putative peroxy zirconium species 5 was expected to
readily undergo ring-opening and to promote B–V oxi-
dation (Scheme 4).
Interaction of the s-orbital of the migrating CꢀC bond
and the s*-orbital of the OꢀO bond is crucial for the
migration.1d Therefore, it was expected that high enan-
tioselectivity would be achieved if the s-bond interacts
with the s*-bond topos-selectively. It was also consid-
ered that the topos-selective interaction would be real-
ized if the Criegee adduct makes a chelate, and the
chelate conformation is regulated appropriately. Fur-
thermore, a metallosalen complex [M(salen)] of cis-b
structure was considered to be a suitable catalyst for
this purpose, because it provides two neighboring coor-
dinating sites for chelate formation and its metal center
is chiral.6
Indeed, Co(salen) 1 of square planar geometry did not
show any enantioselectivity in the B–V oxidation of
3-substituted cyclobutanone, while Co(salen) 2 possess-
ing a cis-b structure showed good enantioselectivity (up
to 78% ee) (Scheme 2).6 However, this result meant that
the control of the chelate conformation by 2 was not
sufficient. To strengthen the control, we tried to modify
complex 2 by introducing a chiral substituent at its 3-
and 3%-carbons but such attempts failed.
Based on this consideration, we examined Zr(salen)-cat-
alyzed B–V reaction of 3-phenylcyclobutanone using
urea·hydrogen peroxide adduct (UHP) as oxidant at
room temperature (Table 1). Complexes 7–10 were
prepared according to the reported procedure with a
O
O
Co-salen complex (5 mol %), Oxidant
O
*
Ph
Ph
yield
% ee
Co(salen)
(R)
1
2
29%
72%
0% ee
(S)
77% ee
N
O
N
+
N
O
N
O
Co
Co
Br
O
Br
F
F
3'
3
SbF6
1
SbF6
Br
Br
F
F
2
Scheme 2.
Ph
Ph
O
O
O
O
O
O-
O
O
N
O
Ti
O
N
N
O
O
N M+
O
M
O
O
N
O
N
O
N
O
N
M
N
Ti
O
N
O
salen ligand
O
N
N
O
4: M= Ti, 5: M= Zr
6: M= Zr
3
Scheme 3.
R= p-ClC6H4: 82% ee (R),13b 63%
R= p-MeOC6H4: 84% ee, 43%
R= n-C8H17: 81% ee, 63%
O
8 (5 mol%), UHP
R
O
H
O
CH2Cl2, r.t.
R
*
O
O
O
H
8 (5 mol%), UHP
H
H
1
H
7
H
94% ee (1S,4R, 7R, 10S),13c 99%
10
CH2Cl2, r.t.
4
H
Scheme 4.

A. Watanabe et al. / Tetrahedron Letters 43 (2002) 4481–4485
4483
Table 1. Asymmetric B–V oxidation of 3-phenylcyclobutanone using Zr(salen) complexes as catalyst
O
Zr-salen Complex (5 mol%), UHP
Ph
O
O
Ph
CH2Cl2, rt
Entry
Catalyst
Yield (%)
% eea
Config.b
1
2
3
4
7
8
9
20
68
13
12
23
87
9
S
R
S
–
10
1
a Determined by HPLC analysis using chiral column (DAICEL CHIRALPAK AD-H, hexane/i-PrOH=49/1).
b Configuration was determined by comparison of specific rotation with the reported ones (see Ref. 13a).
slight modification.9 Among these complexes, complex
8 showed good catalytic activity and high asymmetric
induction. On the other hand, its diastereomeric com-
plex 9 was a poor catalyst, suggesting that the chiral
binaphthyl unit affected the regulation of the chelate
conformation adversely. Complex 10 was also found to
be a poor catalyst.10
Table 2. Effect of terminal oxidant and solvent on enantio-
selectivity of B–V reaction with complex 8
Entry
Oxidant
Solvent
Yield (%)
% eea
1
2
3
4
5
6
UHP
H2O2
TBHP
TMS-O-O-TMS
UHP
UHP
UHP
UHP
UHP
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
PhCl
Et2O
EtOH
CH2Cl2
CH2Cl2
68
60
Trace
11
80
32
44
58
78
87
56
–
4
85
45
52
81
81
We next examined the effect of the terminal oxidant
and solvent on enantioselectivity of the reaction using 8
as the catalyst at room temperature (Table 2). Although
the original condition was found to be the best (Table
1), the reaction in chlorobenzene also showed good
enantioselectivity (entry 5). Use of a polar solvent such
as ether and alcohol reduced enantioselectivity (entries
6 and 7). t-Butyl hydrogenperoxide and bis(trimethylsil-
yl)peroxide were poor oxidants. These results are com-
patible with the above mechanistic consideration: the
presence of bulky t-butyl and silyl groups retards
chelate formation (Scheme 1). The effect of the reaction
temperature was also examined. The reaction rate was
enhanced as the temperature rose, but enantioselectivity
was diminished at either higher or lower temperature
(entries 8 and 9).
7
8b
9c
a Determined by HPLC analysis using chiral column (DAICEL CHI-
RALPAK AD-H, hexane/i-PrOH=49/1).
b Reaction was carried out under 0°C.
c Reaction was carried out under 40°C.
ketone also proceeded with high enantioselectivity of
94% ee in a good yield.
B–V reaction of racemic bicyclo[4.2.0]octan-7-one was
then examined in chlorobenzene. The reaction pro-
ceeded to give normal and abnormal rearrangement
products (A and B).5a,8,11 Enantiomeric excess of major
normal product A was diminished as the reaction pro-
ceeded, while that of minor product B was constantly
greater than 99% (Table 3). The relative reaction ratio
(krel) of fast and slow isomers of the racemic ketone was
Under the best conditions, we examined the reactions
of other 3-substituted cyclobutanones using 8 as the
catalyst. All the reactions proceeded with high enan-
tioselectivity (Scheme 4). The reaction of tricyclic
(R)
(R)
N
Y
Y
N
O
N
N
O
Zr
Zr
tBu
O
tBu
O
Ph Ph
Y
Y
7
(S)
Y
tBu
tBu
(R)
N
O
N
O
(R)
Zr
Y
Y
Ph Ph
N
N
O
8
Zr
(R)
Y
Y= PhO
10
9

4484
A. Watanabe et al. / Tetrahedron Letters 43 (2002) 4481–4485
Table 3. B–V oxidation of racemic bicyclooctanone using Zr(IV)–salen complex 8 as the catalyst
O
O
O
8 (8 mol%), UHP
+
O
O
O
C6H5Cl, r.t.
(trace)
B
A
fast-isomer
O
O
O
8 (8 mol%), UHP
O
+
C6H5Cl, r.t.
(1:5.1)
ent-A
slow-isomer
(racemate)
ent-B
major
minor
Run
Ketone
% eeb
A
B
Conv. (%)a
krel
Yield (%)a
% eeb
Yield (%)a
% eeb
1
2
3
4
5
76
83
76
71
83
86
92
82
77
94
4.2
3.8
3.5
4.1
4.1
54
51
53
48
55
82
82
85
85
80
22
24
21
20
25
\99
\99
\99
\99
\99
a Conversion of racemic ketone and yields of lactones were determined by GLC analysis using bicyclohexyl as the internal standard.
b Determined by GLC analysis using optically active column (SUPELC BETA-DEX-255).
determined to be ca. 4 according to Kagan’s equation.12
These results suggested that the reaction of the fast
isomer gave normal product A exclusively, while the
reaction of the slow isomer gave ent-A and abnormal
product (ent-B) in a ratio of 1:5.1. The reaction of the
optically pure slow isomer with complex 8 provided
normal product A of >99% ee and abnormal product B
of >99% ee in a 1:6.6 ratio. This indicates that the topos
selection by 8 overrides the migratory attitude of the
carbonyl substituent in Baeyer–Villiger reaction.11
Vol. 2, pp. 744–772; (b) Stewart, J. D. Curr. Org. Chem.
1997, 2, 211–232; (c) Kayser, M.; Chen, G.; Stewart, J.
Synlett 1999, 153–158; (d) Kelly, D. R. Chem. Oggi/
Chem. Today 2000, 18, 33–39 and 52–56; (e) Alphand, V.;
Furstoss, R. In Asymmetric Oxidation Reactions: A Prac-
tical Approach; Katsuki, T., Ed.; Oxford University
Press: Oxford, 2001; pp. 214–226.
2. Bolm, C.; Schlingloff, G.; Weickhardt, K. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 1848–1849.
3. Gusso, A.; Baccin, C.; Pinna, F.; Strukul, G.
Organometallics 1994, 13, 3442–3451.
General procedure for asymmetric Baeyer–Villager reac-
tion with Zr(salen) complex 8: 3-Phenylcyclobutanone
(14.6 mg 0.1 mmol) was dissolved in CH2Cl2 (1.0 ml).
To the solution were added complex 8 (5.5 mg, 5.0
mmol) and UHP (12 mg, 0.12 mmol) successively and
the resulting mixture was stirred at room temperature
for 24 h. The mixture was concentrated on a rotary
evaporator and chromatographed on silica gel using a
mixture of hexane and AcOEt (6.5:1) as the eluate to
give b-phenyl-g-butyrolactone (10.9 mg, 68%). The
enantiomeric excess of the product was determined by
HPLC analysis using DAICEL CHIRALPAK AD-H
(hexane:i-PrOH=49:1).
4. (a) Bolm, C.; Beckmann, O. In Comprehensive Asymmet-
ric Catalysis; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H.,
Eds.; Springer: Berlin, 1999; Vol. 2, pp. 803–810; (b)
Strukul, G. Angew. Chem., Int. Ed. Engl. 1998, 37, 1198–
1209.
5. (a) Bolm, C.; Luong, K. K.; Schlingloff, G. Synlett 1997,
1151–1152; (b) Bolm, C.; Beckmann, O.; Cosp, A.;
Palazzi, C. Synlett 2001, 1461–1463; (c) Bolm, C.; Beck-
mann, O.; Palazzi, C. Can. J. Chem. 2001, 79, 1593–1597.
6. Uchida, T.; Katsuki, T. Tetrahedron Lett. 2001, 42, 6911–
6914.
7. (a) Saito, B.; Katsuki, T. Tetrahedron Lett. 2001, 42,
3873–3876; (b) Saito, B.; Katsuki, T. Tetrahedron Lett.
2001, 42, 8333–8336.
In conclusion, we were able to demonstrate that asym-
metric Bayer–Villiger reaction can be effected in a
highly enantioselective manner by using suitably
designed Zr(salen) complex 8 as the catalyst.
8. Zirconium-mediated Baeyer–Villiger oxidation has been
reported. See: Bolm, C.; Beckmann, O. Chirality 2000,
12, 523–525.
9. (a) Schweder, B.; Walther, D.; Do¨hler, T.; Klobs, O.;
Go¨rls, H. J. Prakt. Chem. 1999, 341, 736–746; (b) Wood-
man, P. R.; Munslow, I. J.; Hitchcock, P. B.; Scott, P. J.
Chem. Soc., Dalton Trans. 1999, 4069–4076.
References
10. Although the structure of 10 has not been determined yet,
the structure of the corresponding dichloro complex (Y=
Cl) has been determined to take a cis,cis-structure by
X-ray analysis (Ref. 9b).
1. For recent reviews, see: (a) Alphand, V.; Furstoss, R. In
Handbook of Enzyme Catalysis in Organic Synthesis;
Drauz, K.; Waldmann, H., Eds.; VCH: Weinheim, 1995;

A. Watanabe et al. / Tetrahedron Letters 43 (2002) 4481–4485
4485
11. Migratory attitude of the carbonyl substituent in B–V
oxidation is in the order of tertiary>secondary>primary.
12. Kagan, H. B.; Fiaud, J. C. In Topics in Stereochemistry;
Eliel, E. L.; Wilen, S. H., Eds.; John Wiley & Sons: New
York, 1988; Vol. 18, pp. 249–330.
13. (a) Specific rotation of 4-phenylbutyrolactone (87% ee):
[h]D20=−41.4 (c 0.6, CHCl3); lit.14a [96% ee (S)-isomer];
[h]2D0=+46.0 (c 0.95, CHCl3); (b) Specific rotation of
4-(p-chlorophenylbutyrolactone (82% ee): [h]2D0=−35.9 (c
0.5, CHCl3); lit.14b [>99% ee (R)-isomer]; [h]2D5=−51.0 (c
0.5, CHCl3); (c) Specific rotation of 2-oxatricyclo-
[5.2.1.04,10]decan-3-one (94% ee): [h]2D5=−66.7 (c 0.28,
CHCl3); lit.14c [>98% ee (1R,4S,7S,10R)-isomer]; [h]2D5=
+62.0 (c 1.0, CHCl3).
14. (a) Takaya, Y.; Senda, T.; Kurushima, H.; Ogasawara, M.;
Hayashi, T. Tetrahedron: Asymmetry 1999, 10, 4047–4056;
(b) Mazzini, C.; Lebreton, J.; Alphand, Y.; Furstoss, R.
Tetrahedron Lett. 1997, 38, 1195–1196; (c) Kelly, D. R.;
Knowles, C. J.; Mahdi, J. G.; Wright, M. A.; Taylor, I. N.;
Hibbs, D. E.; Hursthouse, M. B.; Mish’al, A. K.; Roberts,
S. M.; Wan, P. W. H.; Grogan, G.; Willetts, A. J. J. Chem.
Soc., Perkin Trans. 1 1995, 2057–2066.