Asymmetric baeyer-villiger oxidation of 2,3- and 2,3,4-substituted cyclobutanones catalyzed by chiral phosphoric acids with aqueous H 2O2 as the oxidant

Article abstract of DOI:10.1002/ejoc.201001130

Catalytic asymmetric Baeyer-Villiger (B-V) oxidation of 2,3,4-trisubstituted cyclobutanone (4) has been realized by the catalysis of a 1,1′-bi-2-naphthol (BINOL)-derived chiral phosphoric acid (1j), which contains bulky 2,4,6-triisopropyl phenyl groups at the 3,3′-positions of the BINOL backbone, using 30% aqueous H₂O₂ as the oxidant, affording the corresponding Iγ-lactone (5) in 99% yield with 95% ee. In a divergent kinetic resolution of racemic 2,3-disubstituted bicyclic cyclobutanones (6) through asymmetric B-V oxidation, the chiral phosphoric acid 1p demonstrated excellent catalytic performance, giving a range of regioisomeric chiral lactones in a normal lactone (nl)/abnormal lactone (al) ratio of up to 2.1:1, with up to 99% ee in the al product. It was found that fine tuning of the stereoelectronic properties of the backbone in chiral phosphoric acids is critically important for attaining high levels of enantioselectivity in the catalysis of B-V reactions of different type of cyclobutanones. The present work has provided a convenient approach to the synthesis of a variety of optically active chiral Iγ-lactones. Asymmetric Baeyer-Villiger oxidation of tricyclic cyclobutaone and a variety of racemic bicyclic cyclobutanone derivatives has been realized by the catalysis of 1,1′-bi-2-naphthol (BINOL)-derived chiral phosphoric acid with high yields and excellent enantioselectivities using 30% aqueous H₂O₂ as the oxidant.

Full text of DOI:10.1002/ejoc.201001130

FULL PAPER
DOI: 10.1002/ejoc.201001130
Asymmetric Baeyer–Villiger Oxidation of 2,3- and 2,3,4-Substituted
Cyclobutanones Catalyzed by Chiral Phosphoric Acids with Aqueous H2O2 as
the Oxidant
Senmiao Xu,[a] Zheng Wang,[a] Xumu Zhang,[a,b] and Kuiling Ding*[a]
Keywords: Asymmetric catalysis / Oxidation / Hydrogen peroxide / Phosphoric acid
Catalytic asymmetric Baeyer–Villiger (B–V) oxidation of
2,3,4-trisubstituted cyclobutanone (4) has been realized by
the catalysis of a 1,1Ј-bi-2-naphthol (BINOL)-derived chiral
phosphoric acid (1j), which contains bulky 2,4,6-triisopropyl
phenyl groups at the 3,3Ј-positions of the BINOL backbone,
using 30% aqueous H2O2 as the oxidant, affording the corre-
performance, giving a range of regioisomeric chiral lactones
in a normal lactone (nl)/abnormal lactone (al) ratio of up to
2.1:1, with up to 99% ee in the al product. It was found that
fine tuning of the stereoelectronic properties of the backbone
in chiral phosphoric acids is critically important for attaining
high levels of enantioselectivity in the catalysis of B–V reac-
sponding γ-lactone (5) in 99% yield with 95% ee. In a diver- tions of different type of cyclobutanones. The present work
gent kinetic resolution of racemic 2,3-disubstituted bicyclic
cyclobutanones (6) through asymmetric B–V oxidation, the
chiral phosphoric acid 1p demonstrated excellent catalytic
has provided a convenient approach to the synthesis of a
variety of optically active chiral γ-lactones.
aqueous H2O2 as the oxidant, affording a number of chiral
γ-lactones in high yields with good to excellent ee values
(Scheme 1).[8a] A subsequent mechanistic study, which was
based on kinetic measurements and theoretical calculations,
suggested that the chiral phosphoric acid[8b–8ac] functions
as a bifunctional catalyst to simultaneously activate both
the reactants and the Criegee intermediate in the reaction,
and that the enantioselectivity is largely dependent on the
aryl substituents at the 3,3Ј-positions of the catalyst back-
bone.[9] With the aim of further demonstrating the potential
of this type of catalyst, herein we report asymmetric B–V
reactions of a prochiral tricyclic cyclobutanone and a diver-
gent kinetic resolution of racemic bicyclic cyclobutanone
derivatives using 30% aqueous H2O2 as the oxidant.
Introduction
Baeyer–Villiger (B–V) oxidation[1] represents one of the
most important reactions in organic chemistry.[2] The cata-
lytic, enantioselective B–V oxidation of prochiral or race-
mic ketones using environmentally benign oxidants to give
optically enriched lactones has been one of the most chal-
lenging transformations in chiral catalysis. Since the first
reports were independently made by Strukul and co-
workers[3] and Bolm et al.[4] in 1994, a number of chiral
metal complexes and organic molecules have been devel-
oped as catalysts for the oxidation of various prochiral and/
or racemic ketones.[5] However, despite these efforts, wide
substrate generality has not yet been achieved in most cases,
and excellent enantiocontrol in the reaction is usually
achieved mainly by enzymatic systems.[6] On the other
hand, considering the oxidants employed in the B–V reac-
tion, only very few chiral catalyst systems are tolerant of
aqueous hydrogen peroxide as an environmentally benign
oxidant.[3,7] In these regards, we have recently reported the
first example of chiral Brønsted-acid-catalyzed asymmetric
B–V oxidation of 3-substituted cyclobutanones by using
[a] State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai 200032, P. R. of China
Fax: +86-21-6416-6128
E-mail: kding@mail.sioc.ac.cn
[b] Department of Chemistry and Chemical Biology, Center of
Molecular Catalysis, Rutgers, The State University of New
Jersey,
610 Taylor, Piscataway, New Jersey 08854, USA
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001130.
Scheme 1. BINOL-Derived chiral phosphoric-acid-catalyzed enan-
tioselective B–V reaction of 3-substituted cyclobutanones.[8a,9]
110
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Eur. J. Org. Chem. 2011, 110–116

Oxidation of Substituted Cyclobutanones
4; the reaction was performed in CHCl3 at room tempera-
ture with a catalyst loading of 10 mol-% by using 1.5 equiv.
of 30% aqueous H2O2 as the oxidant.
Results and Discussion
Asymmetric B–V Oxidation of Tricyclic Butanone
Tricyclic cyclobutanone 4 has been used as a test prochi-
ral substrate for chemocatalytic asymmetric B–V oxidation,
with good to excellent enantioselectivities being achieved in
some cases.[10] However, to the best of our knowledge, no
report has involved the use of 30% aqueous H2O2 for this
substrate. A preliminary test of the optimized catalyst 1p
for B–V oxidation of 3-substituted cyclobutanones 2 in our
previous communication[8a] revealed that this catalyst only
demonstrated moderate enantioselectivity in the oxidation
of tricyclic cyclobutanone 4 under the experimental condi-
tions shown in Table 1, affording the corresponding γ-lac-
tone product 5 in 96% yield with 67% ee (entry 16). Clearly,
the structure of tricyclic cyclobutanone 4 differs signifi-
cantly from that of 3-substituted cyclobutanones 2. The
above mentioned preliminary result showed that the oxi-
dation of substrates with distinct structural features re-
quires a substrate–catalyst mutual match to realize maximal
asymmetric induction and catalytic activity in the reaction.
Accordingly, the catalytic performance of a variety of 1,1Ј-
bi-2-naphthol (BINOL)-derived chiral phosphoric acids 1a–
r with diverse steric and electronic properties of the 3,3Ј-
substituents and the skeleton (Figure 1) was subsequently
examined in the B–V oxidation of tricyclic cyclobutanone
Figure 1. BINOL-derived chiral phoposphoric acids used in this
study.
The results are summarized in Table 1. In general, the
chiral phosphoric acids constitute a class of efficient cata-
lysts for this reaction, with yields of the lactone product 5
ranging from 91 to 99% in all cases, however, the enantio-
selectivity varied widely (4–87% ee) depending on the de-
tailed structural motifs of the catalyst. Changing the rigid
binaphthyl backbone of 1l or 1m to the conformationally
more flexible H8-binaphthyl of 1o or 1p did not much effect
the enantioselectivity (Table 1, entries 12 vs. 15 and 13 vs.
16), and the ee values of 5 remained moderate (64–69%) in
these cases. On the other hand, the enantioselectivity of the
reaction was found to be highly sensitive to slight variations
in the stereoelectronic features of the 3,3Ј-subustitents on
the catalyst backbone. Clearly, the incorporation of elec-
tron-withdrawing groups into the 3,3Ј-substituents of the
phosphoric acids (1c and 1d) was unfavorable for the reac-
tion, giving lactone 5 with only modest ee values (Table 1,
entries 3–4). Although the steric bulk of the 3,3Ј-aryl sub-
stituents generally exhibited a beneficial effect on the
enantioselectivity (Table 1, entries 1, 5, and 8), the trend
was less clear in several cases and the distinct spatial orien-
tation of the substituents seems to also play a role (e.g.,
entries 5 vs. 6 and 1 vs. 7). Among the phosphoric acids
screened for the reaction, 1j, with the bulky 2,4,6-triiso-
propyl phenyl groups at the 3,3-positions of the catalyst
backbone, was found to be optimal in terms of the enantio-
selectivity, affording 5 in almost quantitative yield with
good enantioselectivity (87% ee; Table 1, entry 10).
Table 1. Asymmetric B–V oxidation of the tricyclic cyclobutanone
4 in the presence of chiral phosphoric acid 1a–q.[a]
Entry
Cat.
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1r
97
99
99
99
99
99
95
99
99
99
99
99
99
99
91
96
99
31
43
19
4
56
32
34
66
29
87
48
68
64
75
69
67
55
9
10
11
12
13
14
15
16
17
Further attempts to improve the enantioselectivity of 1j-
catalyzed B–V oxidation of 4 were undertaken by changing
the reaction solvent and the reaction temperature. The re-
sults are summarized in Table 2. Clearly, both parameters
have an impact on the catalytic efficiency and enantio-
selectivity. Nearly quantitative yields and good ee values
(84–89%) of the product were obtained for the reactions
[a] Reagents and conditions: 4 (0.1 m in CHCl3), aq. H2O2 (30%,
1.5 equiv.), room temp. [b] Yield of isolated product. [c] The enan-
tiomeric excess of 5 was determined by chiral GC (Suplco Beta
Dex 225). The absolute configuration of 5 was determined to be
1S,4R,7R,10S by comparison of its optical rotation with that re-
ported in the literature.[11c]
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111

K. Ding et al.
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Table 2. Solvent and temperature effects on 1j-catalyzed asymmet- carried out at room temp. in toluene or halogen-containing
ric B–V oxidation of tricyclic cyclobutanone 4.[a]
solvents (Table 2, entries 1–5). Under otherwise identical
conditions, the reaction performed in n-hexane was more
sluggish (Table 2, entry 7), whereas the catalysis in diethyl
ether gave lactone 5 with only modest enantioselectivity
(19% ee; Table 2, entry 6). Although the reaction in toluene
took a prolonged period to reach completion at reduced
temperatures, this was beneficial for the enantioselectivity
as evidenced by the enhanced ee values (from 88 to 95%)
achieved when the reaction temperature was varied from
room temp. to –40 °C (Table 2, entries 4 and 8–10). Further
decreasing the temperature to –50 °C gave no further im-
provement on the ee value of the product (Table 2, entry
11).
Entry Solvent
Temp.
[°C]
Time
[h]
Yield
[%][b]
ee
[%][c]
1
2
3
4
5
6
CHCl3
25
25
25
25
25
25
25
0
2
2
2
2
2
2
8
12
12
24
24
99
99
92
99
99
99
92
99
99
99
99
87
88
87
88
89
19
84
91
93
95
95
CH2Cl2
ClCH2CH2Cl
toluene
F3CC6H5
Et2O
7
8
9
10
11
n-hexane
toluene
toluene
toluene
toluene
Asymmetric B–V Oxidation of Racemic Bicyclic
Cyclobutanones
–20
–40
–50
Divergent kinetic resolution of racemic cyclobutanones
constitutes an important asymmetric B–V transforma-
tion.[11] As a result of the combined action of the distinct
migratory aptitudes of ketonic alkyls on the substrate and
the asymmetric induction of the chiral catalyst, such B–V
reactions would usually lead to two regioisomeric lactones
[a] Reagents and conditions: 4 (0.1 m), aq. H2O2 (30%, 1.5 equiv.).
[b] Yield of isolated product. [c] The enantiomeric excess of 5 was
determined by chiral GC on a Suplco Beta Dex 225. The absolute
configuration of 5 was determined to be 1S,4R,7R,10S by compari-
son of its optical rotation with that reported in the literature.[11c]
Table 3. Asymmetric B–V oxidation of racemic cyclobutanone 6a in the presence of chiral phosphoric acid 1a–q.[a]
Entry
Cat.
Time [h]
Solvent
Yield [%][b]
nl/al[c]
nl, ee [%][d]
al, ee [%][d]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
24
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
24
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
ClCH2CH2Cl
toluene
CF3C6H5
Et2O
99
99
99
99
99
99
99
99
99
99
99
99
99
99
99
99
99
99
99
99
94
99
3.7:1
4.0:1
4.2:1
4.0:1
2.0:1
4.1:1
3.6:1
2.7:1
3.3:1
2.7:1
1.6:1
1.5:1
1.3:1
1.3:1
2.5:1
1.7:1
1.6:1
2.1:1
2.1:1
4.1:1
3.3:1
2.2:1
7
6
9
0
23
8
11
21
12
29
43
49
48
56
28
47
51
34
37
9
–4
24
33
0
42
29
44
59
39
86
67
78
65
76
74
86
84
72
79
30
46
94
9
10
11
12
13
14
15
16
17
18
19
20
21
22[e]
1j
1l
1m
1o
1p
1k
1p
1p
1p
1p
1p
1p
1p
n-hexane
CH2Cl2
14
38
[a] Reagents and conditions: 6a (0.1 m), aq. H2O2 (30%, 1.5 equiv.), room temp. [b] Total yield of isolated products 7a and 8a. [c] The
1
ratio of 7a/8a was determined by H NMR spectroscopic analysis of the isolated mixture of the isomeric lactones. [d] The enantiomeric
excesses of 7a and 8a were determined by chiral HPLC analysis with a Chiralpak OD column; their absolute configurations were not
assigned. [e] The reaction was carried out at –40 °C.
112
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Oxidation of Substituted Cyclobutanones
in optically enriched forms, sometimes together with unre- aqueous H2O2 has never been reported. On the basis of our
acted ketone, by kinetic resolution.[12] The product gener- previous results with the chiral phosphoric acid-catalyzed
ated by migration of the group that is in accord with mi- asymmetric B–V oxidation of 3-substituted cyclobutanones
gratory aptitude is defined as the normal lactone (abbrevi- 2,[8,9] and on the tricyclic cyclobutanone 4 mentioned above,
ated as nl) and the product generated by migration of the we further explored the possibility of applying this ap-
group in contravention of the migratory aptitude is thus proach to the oxidation of racemic 2,3-disubstituted bicy-
defined as the abnormal lactone (abbreviated as al).[10e] In clic cyclobutanones 6 using chiral phosphoric acid as the
fact, asymmetric B–V oxidation of racemic ketones is a catalyst and 30% aqueous H2O2 as the oxidant. As shown
well-documented reaction that has previously been in the in Table 3, the chiral phosphoric acid 1b was found to be
domain of enzyme catalysis.[6] A variety of chiral transition- efficient in the B–V oxidation of racemic cyclobutanone 6a,
metal complexes have also been shown to catalyze such re- albeit giving low ee values (Ͻ10%) for both products (7a
actions, giving the lactones with high optical purity in some and 8a; Table 3, entry 1). The normal lactone 7a is gener-
cases.[3,4,7c–7e,10,11] Although significant achievements have ated by following the migratory aptitude rule and, concomi-
been made with metal complex catalysts,[11a,11b,11d,11e,12] to tantly, the abnormal lactone 8a results from migration of
the best of knowledge, the direct use of organocatalysts and the less substituted carbon atom. Under the stereoelectronic
Table 4. Asymmetric B–V oxidation of racemic bicyclic cyclobutanones 6a–j in the presence of chiral phosphoric acid 1p.[a]
[a] Reagents and conditions: 6 (0.1 m), aq. H2O2 (30%, 1.5 equiv.), –40 °C. [b] Total yield of isolated products 7 and 8. [c] For entries 1–
7, the ratio of nl/al was determined by 1H NMR spectroscopic analysis; for entries 8–11, the ratio of nl/al was determined by GC analysis.
[d] For entries 1–7, the enantiomeric excesses of 7 and 8 were determined by HPLC analysis with a chiral column; for entries 8–11, the
enantiomeric excesses of 7 and 8 were determined by GC analysis with a chiral column. The absolute configurations were not assigned.
[e] The reaction was carried out at room temp. [f] The peaks were not well-resolved on the HPLC chromatograph.
Eur. J. Org. Chem. 2011, 110–116
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113

K. Ding et al.
FULL PAPER
control of a suitable chiral catalyst, nl and/or al might be fied period of reaction time (Table 4). In all cases, the nl
obtained with good conversion and high ee values. Using products 7a–j were formed as the preferential regioisomers
the racemic bicyclic cyclobutanone 6a as a model substrate, (nl/al = 2.1 to 11.5), which is in agreement with the mi-
we subsequently screened the chiral phosphoric acids 1a–q gratory aptitude for B–V reactions. Whereas the enantio-
for their ability to catalyze the reaction with 30% H2O2 as selectivities for the nl products were generally only modest
the oxidant. As shown in Table 3, performing the reactions (7–38% ee), they were far higher for the corresponding
in chloroform led to complete conversion of the substrates minor al isomers 8a–j, which had ee values ranging from
after 12–24 h at room temp., and resulted in the clean for- good to excellent (74–99% ee).
mation of 7a and 8a in quantitative yields. A moderate to
high preference for the nl product 7a (nl/al = 1.3–4.2) was
observed in all cases, which is consistent with the migratory
Conclusions
aptitude for B–V reactions. The enantioselectivity for both
products varied widely within the series of the chiral phos-
phoric acid catalysts, ranging from 0–56 for 7a and 0–86
for 8a, respectively. For each chiral phosphoric acid, the
The asymmetric B–V oxidation of tricyclic cyclobut-
anone 4 using 30% aqueous H2O2 as the oxidant proceeds
smoothly under the catalysis of chiral phosphoric acids to
afford the corresponding chiral γ-lactone 5 in quantitative
ratio of the ee values of the two regioisomers 7a and 8a
yield with up to 95% ee. The chiral phosphoric acids were
was approximately equal to the inverse ratio of their relative
also found to be efficient catalysts for the asymmetric B–V
reaction of various racemic bicyclic cyclobutanone deriva-
tives. The reaction gave a range of chiral lactones with the
nl products as the major regioisomer in moderate to high
nl/al ratios, whereas the minor al isomers could be obtained
with good to excellent ee values. It was found that fine tun-
ing of the stereoelectronic properties of the backbone in the
amounts.[12] Substituents at the 3,3Ј-positions of the bi-
naphthyl scaffold of the catalyst play a critical role in con-
trolling both regioselectivity and enantioselectivity of this
series of reactions, although it is difficult to correlate these
selectivities with structural features of the catalyst. Herein,
the factors that control the stereoselectivity seem to work
in parallel with those discussed above for B–V oxidation of
chiral phosphoric acids is critically important for attaining
tricyclic ketone 4, i.e., the 3,3Ј-substituents at the catalyst
high levels of enantioselectivity in the catalysis of B–V reac-
tions with different types of cyclobutanones. The present
backbone should be sufficiently bulky (Table 3, entries 10–
14) and adopt a suitable orientation (Table 3, entries 5 vs.
work has provided a convenient approach to the synthesis
6) to favor good ee values for both isomers, whereas the
of a variety of optically active chiral γ-lactones.
presence of less bulky 3,3Ј-substituents (Table 3, entries 1
and 2) or some strongly electron-withdrawing groups
(Table 3, entries 3 and 4) on the catalyst is disadvantageous
for the enantioselectivity. In short, in the presence of cata-
lysts with sterically more encumbering groups (see 1j–p),
the products 7a and 8a were both obtained in moderate to
good ee values, together with a somewhat enhanced regiose-
lectivity towards the al product (Table 3, entries 10–14).
Solvent and temperature effects on the B–V oxidation of
racemic 6a was further investigated with 1p as the catalyst
Experimental Section
General Methods: NMR spectra were recorded with a Varian Mer-
cury 300 (1H: 300 MHz) or a Varian 400-MR (1H: 400 MHz) spec-
trometer with samples dissolved in CDCl3. Chemical shifts are ex-
pressed in ppm with TMS as an internal standard (δ = 0 ppm) for
1H NMR spectroscopic data. Coupling constants (J) are listed in
Hertz. HPLC analysis was carried out with a JASCO PU 2089 or
a JASCO 1589 instrument. GC analysis was performed with an Ag-
under conditions that were otherwise identical to those de-
scribed above. Whereas the reactions proceeded smoothly
in all the tested solvents, both the regioselectivity and the
enantioselectivity varied significantly with the solvent used.
In general, chlorinated solvents favored both higher
enantioselectivity and regioselectivity for the al product 8a
(Table 3, entries 14 and 16–17). As expected, the reaction
temperature also had a remarkable effect on the regioselec-
tivity and enantioselectivities. When the reaction was car-
ilent 6890N instrument. Unless stated otherwise, all solvents were
purified and dried according to standard methods prior to use.
Typical Procedure for the Asymmetric B–V Reaction of Tricyclic
Cyclobutanone 4 Catalyzed by Chiral Phosphoric Acid 1j and Aque-
ous H2O2 as Oxidant: A 5-mL Schlenk tube was charged with 1j
(7.5 mg, 0.01 mmol), tricyclic cyclobutanone 4 (14 mg, 0.1 mmol),
and toluene (1 mL). The mixture was cooled and stirred at –40 °C
before 30% H2O2 (17 μL, 0.15 mmol) was added, and the resulting
ried out at –40 °C, the ee value of al was enhanced up to mixture was stirred for 24 h at this temperature. The reaction was
quenched by addition of an aqueous solution of Na2SO3 (0.1 mL),
and the product 5 was purified by column chromatography on silica
gel (petroleum ether/ethyl acetate, 6:1) in 99% yield. [α]2D0 = –66.5
(c 0.71, CHCl3), 95% ee [ref.[10c] [α]2D0 = +62 (c 1.0, CHCl3) for
(1R,4S,7S,10R)-isomer with Ͼ98% ee]. 1H NMR (400 MHz,
CDCl3): δ = 4.94 (dd, J = 10.8, 2.8 Hz, 1 H), 3.17–3.20 (m, 1 H),
3.05–3.09 (m, 1 H), 2.62–2.65 (m, 1 H), 2.07–2.18 (m, 3 H), 1.82
(m, 3 H), 1.44–1.54 (m, 2 H) ppm; The enantiomeric excess was
determined by chiral GC analysis on a Chiralcel Supelco BETA-
DEX 225 column (column temperature = 160 °C, N2 flow rate =
94%, albeit with a concomitant decrease in its proportion
in the product mixture (Table 3, entries 16 vs. 22).
A variety of chiral racemic bicyclic cyclobutanone deriv-
atives were then examined as substrates for the asymmetric
B–V reactions, which were performed with 0.1 molar equiv-
alent of phosphoric acid 1p as the catalyst and 1.5 equiva-
lent of 30% aqueous H2O2 as the oxidant. The reactions
proceeded smoothly in dichloromethane at–40 °C, leading
to clean formation of the corresponding normal lactones
and abnormal lactones in excellent yields within the speci- 1.0 mL/min), tR = 12.4 min (minor), tR = 13.5 min (major).
114 Eur. J. Org. Chem. 2011, 110–116
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Oxidation of Substituted Cyclobutanones
Oxidation Reactions: A Practical Approach (Ed.: T. Katsuki),
Oxford University Press, Oxford, 2001, p. 214–226; c) S. M.
Roberts, P. W. H. Wan, J. Mol. Catal. B 1998, 4, 111–136. For
recent examples, see: d) M. T. Reetz, S. Wu, J. Am. Chem. Soc.
2009, 131, 15424–15432; e) C. Rodriguez, G. de Gonzalo,
D. E. T. Pazmino, M. W. Fraaije, V. Gotor, Tetrahedron: Asym-
metry 2009, 20, 1168–1173; f) C. Rodriguez, G. de Gonzalo,
D. E. T. Pazmino, M. W. Fraaije, V. Gotor, Tetrahedron: Asym-
metry 2008, 19, 197–203; g) C. Rodriguez, G. de Gonzalo,
M. W. Fraaije, V. Gotor, Tetrahedron: Asymmetry 2007, 18,
1338–1344; h) F. Rudroff, J. Rydz, F. H. Ogink, M. Fink, M. D.
Mihovilovic, Adv. Synth. Catal. 2007, 349, 1436–1444.
Typical Procedure for Asymmetric B–V Reaction of Racemic Bicy-
clic Cyclobutanones 6a Catalyzed by Chiral Phosphoric Acid 1p and
30% H2O2 as Oxidant: A 5-mL Schlenk tube was charged with 1p
(0.01 mmol), racemic cyclobutanone 6a (0.1 mmol), and CH2Cl2
(1 mL). The mixture was cooled and stirred at –40 °C before 30%
aqueous H2O2 (17 μL, 0.15 mmol) was added, and the resulting
mixture was stirred for 12–36 h at this temperature. After comple-
tion of the reaction, the residual H2O2 was quenched with aqueous
Na2SO3 (0.1 mL), and the normal lactone 7a and abnormal lactone
8a were isolated as a regioisomeric mixture by column chromatog-
raphy on silica gel (petroleum ether/ethyl acetate, 6:1) in 99% yield.
The 7a/8a ratio was determined by comparison of the integration
[7] a) C. Paneghetti, R. Gavagnin, F. Pinna, G. Strukul, Organo-
metallics 1999, 18, 5057–5065; b) S. Murahashi, S. Ono, Y. Im-
ada, Angew. Chem. 2002, 114, 2472–2474; Angew. Chem. Int.
Ed. 2002, 41, 2366–2368; c) M. Colladon, A. Scarso, G.
Strukul, Synlett 2006, 3515–3520; d) A. Cavarzan, G. Bianch-
ini, P. Sgarbossa, L. Lefort, S. Gladiali, A. Scarso, G. Strukul,
Chem. Eur. J. 2009, 15, 7930–7939; e) G. Bianchini, A. Cavar-
zan, A. Scarso, G. Strukul, Green Chem. 2009, 11, 1517–1520.
There are also some reports on the use of a urea–hydrogen
peroxide adduct (UHP) as oxidant for catalytic asymmetric B–
V reactions, see, for examples: f) T. Uchida, T. Katsuki, Tetra-
hedron Lett. 2001, 42, 6911–6914; g) A. V. Malkov, F. Friscourt,
1
values of the relevant H NMR signals at δ = 5.28–5.33 ppm (7a)
and δ = 4.69 ppm (8a) for the isomeric mixture.[10e]
1
Mixture of Compounds 7a and 8a: H NMR (300 MHz, CDCl3): δ
= 7.23–7.29 (m), 5.28–5.33 (m), 4.69 (dd, J = 9.3, 6.3 Hz), 4.53 (dd,
J = 9.3, 1.2 Hz), 3.98–4.09 (m), 3.31–3.40 (m), 3.05 (dd, J = 18.0,
9.3 Hz), 2.75 (dd, J = 17.7, 1.2 Hz) ppm. The enantiomeric excess
was determined by chiral HPLC analysis on a Chiralpak OD col-
umn (hexane/iPrOH = 95:5, flow rate: 0.7 mL/min, λ = 214 nm),
tR = 38.3 min (minor) and 53.5 min (major) for the two enantio-
mers of 7a, respectively; tR = 35.7 min (major), 48.3 min (minor)
for the two enantiomers of 8a, respectively. The peak assignments
were made by comparison with chromatographs of the correspond-
ing racemic lactones. The absolute configurations for these isomers
were not assigned.
M. Bell, M. E. Swarbrick, P. Kocovský, J. Org. Chem. 2008,
ˇ
73, 3996–4003.
[8] a) S. Xu, Z. Wang, X. Zhang, X. M. Zhang, K. Ding, Angew.
Chem. 2008, 120, 2882–2885; Angew. Chem. Int. Ed. 2008, 47,
2840–2843. Chiral phosphoric acids have been established as
one type of extremely versatile organocatalysts in asymmetric
catalysis; for reviews, see: b) T. Akiyama, Chem. Rev. 2007, 107,
5744–5758; c) A. G. Doyle, E. N. Jacobsen, Chem. Rev. 2007,
107, 5714–5743; d) M. Terada, Chem. Commun. 2008, 4097–
4112; e) D. Kampen, C. M. Reisinger, B. List, in: Asymmetric
Organocatalysis, Springer-Verlag Berlin, Berlin, 2010, vol. 291,
p. 395–456. For selected recent examples, see: f) S. Liao, B.
List, Angew. Chem. 2009, 121, 638–641; Angew. Chem. Int. Ed.
2009, 48, 628–631; g) M. Rueping, A. P. Antonchick, E. Su-
giono, K. Grenader, Angew. Chem. 2009, 121, 925–927; Angew.
Chem. Int. Ed. 2009, 48, 908–910; h) T. Akiyama, T. Katoh, K.
Mori, Angew. Chem. 2009, 121, 4290–4292; Angew. Chem. Int.
Ed. 2009, 48, 4226–4228; i) T. Yue, M.-X. Wang, D.-X. Wang,
G. Masson, J. Zhu, Angew. Chem. 2009, 121, 6845–6849; An-
gew. Chem. Int. Ed. 2009, 48, 6717–6721; j) Q. W. Zhang, C. A.
Fan, H. J. Zhang, Y. Q. Tu, Y. M. Zhao, P. Gu, Z. M. Chen,
Angew. Chem. 2009, 121, 8724–8726; Angew. Chem. Int. Ed.
2009, 48, 8572–8574; k) K. Mori, T. Katoh, T. Suzuki, T. Noji,
M. Yamanaka, T. Akiyama, Angew. Chem. 2009, 121, 9832–
9834; Angew. Chem. Int. Ed. 2009, 48, 9652–9654; l) M. Hat-
ano, K. Moriyama, T. Maki, K. Ishihara, Angew. Chem. 2010,
122, 3911–3914; Angew. Chem. Int. Ed. 2010, 49, 3823–3826;
m) V. N. Wakchaure, J. Zhou, S. Hoffmann, B. List, Angew.
Chem. 2010, 122, 4716–4718; Angew. Chem. Int. Ed. 2010, 49,
4612–4614; n) W. Zheng, L. Wojtas, J. C. Antilla, Angew. Chem.
Int. Ed., DOI: 10.1002/anie.201002972; o) N. Li, X.-H. Chen,
S.-M. Zhou, S.-W. Luo, J. Song, L. Ren, L.-Z. Gong, Angew.
Chem. Int. Ed. 2010, 49, DOI: 10.1002/anie.201001723; p) M.
Terada, H. Tanaka, K. Sorimachi, J. Am. Chem. Soc. 2009,
131, 3430–3431; q) Q. Gu, Z.-Q. Rong, C. Zheng, S.-L. You,
J. Am. Chem. Soc. 2009, 131, 4056–4057; r) L. Simn, J. M.
Goodman, J. Am. Chem. Soc. 2009, 131, 4070–4077; s) M. Lu,
D. Zhu, Y. P. Lu, X. F. Zeng, B. Tan, Z. J. Xu, G. F. Zhong, J.
Am. Chem. Soc. 2009, 131, 4562–4563; t) H. Liu, G. Dagousset,
G. Masson, P. Retailleau, J. P. Zhu, J. Am. Chem. Soc. 2009,
131, 4598–4599; u) M. Terada, Y. Toda, J. Am. Chem. Soc.
2009, 131, 6354–6355; v) C. Q. Li, B. Villa-Marcos, J. L. Xiao,
J. Am. Chem. Soc. 2009, 131, 6967–6969; w) Z.-Y. Han, H.
Xiao, X.-H. Chen, L.-Z. Gong, J. Am. Chem. Soc. 2009, 131,
9182–9183; x) M. E. Muratore, C. A. Holloway, A. W. Pilling,
R. I. Storer, G. Trevitt, D. J. Dixon, J. Am. Chem. Soc. 2009,
131, 10796–10797; y) N. Momiyama, H. Tabuse, M. Terada, J.
Supporting Information (see also the footnote on the first page of
this article): Detailed experimental procedure and product charac-
terization for the catalytic asymmetric B–V oxidation of racemic
cyclobutanone 6.
Acknowledgments
Financial support from the National Natural Science Foundation
of China (grant number 20821002, 20923005), the Chinese Acad-
emy of Sciences, the Major Basic Research Development Program
of China (grant number 2010CB833300), and the Science and Tech-
nology Commission of Shanghai Municipality is gratefully ac-
knowledged.
[1] A. Baeyer, V. Villiger, Ber. Dtsch. Chem. Ges. 1899, 32, 3625–
3633.
[2] a) G. R. Krow, Org. React. 1993, 43, 251–798; b) M. Renz, B.
Meunier, Eur. J. Org. Chem. 1999, 737–750; c) G. Strukul, An-
gew. Chem. 1998, 110, 1256–1267; Angew. Chem. Int. Ed. 1998,
37, 1198–1209; d) C. Bolm, in: Advances in Catalytic Processes
(Ed.: M. P. Doyle), JAI Press, Greenwich, 1997, vol. 2, p. 43–
68.
[3] A. Gusso, C. Baccin, F. Pinna, G. Strukul, Organometallics
1994, 13, 3442–3451.
[4] C. Bolm, G. Schlingloff, K. Weickhardt, Angew. Chem. 1994,
106, 1994–1946; Angew. Chem. Int. Ed. Engl. 1994, 33, 1848–
1849.
[5] For reviews, see: a) C. Bolm, O. Beckmann, in: Comprehensive
Asymmetric Catalysis (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yam-
amoto), Springer, Berlin, 1999, vol. 2, p. 803–810; b) C. Bolm,
C. Palazzi, O. Bechmann, in: Transition Metals for Organic
Chemistry: Building Blocks and Fine Chemicals (Eds.: M. Beller,
C. Bolm), Wiley-VCH, Weinheim, 2nd ed., 2004, vol. 2, p. 267–
274; c) C. Bolm, in: Asymmetric Synthesis – The Essentials
(Eds.: M. Christmann, S. Bräse), Wiley-VCH, Weinheim, 2006,
p. 57–61; see also ref.[2c]
[6] For reviews, see: a) M. D. Mihovilovic, Curr. Org. Chem. 2006,
10, 1265–1287; b) V. Alphand, R. Furstoss, in: Asymmetric
Eur. J. Org. Chem. 2011, 110–116
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
115

K. Ding et al.
FULL PAPER
Am. Chem. Soc. 2009, 131, 12882–12883; z) X. H. Chen, Q. [11]
Wei, S. W. Luo, H. Xiao, L. Z. Gong, J. Am. Chem. Soc. 2009,
131, 13819–13825; aa) N. Li, X.-H. Chen, J. Song, S.-W. Luo,
W. Fan, L.-Z. Gong, J. Am. Chem. Soc. 2009, 131, 15301–
15310; I. Coric, S. Vellalath, B. List, J. Am. Chem. Soc. 2010,
132, 8536–8537; ac) O. Lifchits, C. M. Reisinger, B. List, J. Am.
Chem. Soc. 2010, 132, 10227–10229.
a) C. Bolm, G. Schlingloff, J. Chem. Soc., Chem. Commun.
1995, 1247–1248; b) C. Bolm, O. Beckman, Chirality 2000, 12,
523–525; c) C. Bolm, O. Beckmann, C. Palazzi, Can. J. Chem.
2001, 79, 1593–1597; d) C. Bolm, O. Beckmann, T. Kühn, C.
Palazzi, W. Adam, P. B. Rao, C. R. Saha-Möller, Tetrahedron:
Asymmetry 2001, 12, 2441–2446; e) J.-C. Frison, C. Palazzi, C.
Bolm, Tetrahedron 2006, 62, 6700–6706.
[9] S. Xu, Z. Wang, Y. Li, X. M. Zhang, H. Wang, K. Ding, Chem.
Eur. J. 2010, 16, 3021–3035.
[12] For reviews on the general aspects of the reaction of a chiral
catalyst or reagent with a racemic or enantiopure substrate,
including asymmetric B–V reaction of racemic chiral ketones
mediated by chiral catalysts, see: a) H. B. Kagan, Tetrahedron
2001, 57, 2449–2459; b) R. R. Kumar, H. B. Kagan, Adv.
Synth. Catal. 2010, 352, 231–242.
[10] For examples, see: a) C. Bolm, T. K. R. Luong, G. Shlingloff,
Synlett 1997, 1151–1152; b) K. Ito, A. Ishii, T. Kuroda, T. Kat-
suki, Synlett 2003, 643–646; c) T. Uchida, T. Katsuki, Helv.
Chim. Acta 2002, 85, 3078–3089; d) A. Watanabe, T. Uchida,
K. Ito, T. Katsuki, Tetrahedron Lett. 2002, 43, 4481–4485; e)
A. Watanabe, T. Uchida, R. Irie, T. Katsuki, Prod. Natl. Acad.
Sci. USA 2004, 101, 5737–5742.
Received: August 12, 2010
Published Online: November 19, 2010
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Eur. J. Org. Chem. 2011, 110–116