Enantioselective oxidation of alkenylbenzoates catalyzed by chiral hypervalent iodine(III) to yield 4-hydroxyisochroman-1-ones

Article abstract of DOI:10.1002/ejoc.201300959

In this study, the enantioselective oxylactonization of ortho-alk-1-enylbenzoates with chiral hypervalent iodine(III) reagents yielded 3-alkyl-4-hydroxyisochroman-1-ones with high enantiomeric purity (ca. 90 % ee). The enantioselective oxidation was also performed under catalytic conditions, in which a catalytic amount (10 mol-%) of a chiral iodoarene was oxidized to the hypervalent iodine species in situ using a stoichiometric co-oxidant, m-chloroperbenzoic acid (mCPBA). The catalytic oxidation mediated by chiral hypervalent iodine(III) species yielded enantiocontrolled syn products, while the direct oxidation of the substrate with mCPBA occurred as background oxidation to give racemic anti products. Under optimized conditions, the catalytic oxylactonization led to high levels of enantioselectivity (ca. 90 % ee) and improved syn/anti selectivities (ca. 80 % syn). The product distribution indicated that the lactate side-chain on the chiral iodoarene precatalyst plays an important role in enhancing both the enantioselectivity and the catalytic efficiency in the oxylactonization. Organocatalytic oxidation mediated by chiral hypervalent iodine derivatives provides a concise route to optically active 4-hydroxyisochroman-1-ones. The lactate moiety of the iodoarene precatalyst plays an important role in enhancing both the enantioselectivity and the catalytic efficiency. This reaction should set the basis for synthetic routes to many 4-hydroxyisochoman-1-one natural products and their analogs. Copyright

Full text of DOI:10.1002/ejoc.201300959

FULL PAPER
DOI: 10.1002/ejoc.201300959
Enantioselective Oxidation of Alkenylbenzoates Catalyzed by Chiral
Hypervalent Iodine(III) To Yield 4-Hydroxyisochroman-1-ones
Mio Shimogaki,[a] Morifumi Fujita,*[a] and Takashi Sugimura[a]
Keywords: Asymmetric synthesis / Organocatalysis / Hypervalent compounds / Oxidation / Lactones
In this study, the enantioselective oxylactonization of ortho-
ucts, while the direct oxidation of the substrate with mCPBA
alk-1-enylbenzoates with chiral hypervalent iodine(III) rea- occurred as background oxidation to give racemic anti prod-
gents yielded 3-alkyl-4-hydroxyisochroman-1-ones with
high enantiomeric purity (ca. 90% ee). The enantioselective
oxidation was also performed under catalytic conditions, in
which a catalytic amount (10 mol-%) of a chiral iodoarene
was oxidized to the hypervalent iodine species in situ using
ucts. Under optimized conditions, the catalytic oxylacton-
ization led to high levels of enantioselectivity (ca. 90% ee)
and improved syn/anti selectivities (ca. 80% syn). The prod-
uct distribution indicated that the lactate side-chain on the
chiral iodoarene precatalyst plays an important role in en-
hancing both the enantioselectivity and the catalytic effi-
ciency in the oxylactonization.
a
stoichiometric co-oxidant, m-chloroperbenzoic acid
(mCPBA). The catalytic oxidation mediated by chiral hyper-
valent iodine(III) species yielded enantiocontrolled syn prod-
Introduction
The 4-hydroxyisochromanone motif is found in many
natural products (Figure 1), most of which belong to a fam-
ily of polyketide metabolites isolated from fungal and bac-
terial sources.[1–7] These oxyisochromanones show interest-
ing biological activities such as antifungal, antibacterial,
and cytotoxic effects. Despite the simple structures and
promising biological properties of the oxyisochromanones,
the synthesis of this class of natural products remains a sig-
nificant challenge, and only a few successful total syntheses
have been reported.[8–10]
Two strategies have been reported for the synthesis of 4-
hydroxyisochroman-1-one derivatives: 1) the hetero-Diels–
Alder cycloaddition of ortho-quinone dimethides followed
by oxidation[11] (the first pathway in Scheme 1); and 2) the
oxidative rearrangement of isobenzofurans followed by re-
duction[12] (the second pathway). However, an enantioselec-
tive transformation has not been achieved using either of
these strategies. Meanwhile, we have recently presented a
third method for the selective preparation of 4-oxyiso-
chroman-1-ones using hypervalent iodine(III) reagents (the
third pathway in Scheme 1).[13] Using lactate-based chiral
hypervalent iodine reagents led to high levels of enantio-
selectivity in the oxylactonization of ortho-alkenylbenzoate
1. The endo selectivity achieved in the oxylactonization with
hypervalent iodine contrasts with the exo selectivity ob-
Figure 1. Natural products containing the 4-hydroxyisochroman-1-
one motif.
[a] Graduate School of Material Science, University of Hyogo,
Kohto, Kamigori, Hyogo 678-1297, Japan
E-mail: fuji@sci.u-hyogo.ac.jp
served in the reaction with conventional oxidizing rea-
gents.[14,15] The unprecedented regioselectivity in the oxyl-
actonization with hypervalent iodine opens up a powerful
www.sci.u-hyogo.ac.jp
Supporting information for this article is available on the
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7128
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Eur. J. Org. Chem. 2013, 7128–7138

Enantioselective Oxidation of Alkenylbenzoates
approach to the synthesis of 4-hydroxyisochroman-1-one cally.[26,27] Many enantioselective oxidations using chiral
natural products. In fact, the oxylactonization strategy hypervalent iodine reagents have been performed under
using hypervalent iodine has been applied to the asymmet- catalytic conditions[22,24,25] in which a catalytic amount of
ric synthesis of more than four types of 4-oxyisochroman- a chiral iodoarene was oxidized to give a hypervalent iodine
1-one natural products, including 4-hydroxymellein and a species in situ using a stoichiometric co-oxidant, as shown
fusarentin-related compound.[9,13]
in Scheme 2. In the catalytic variant of the reaction, it is
no longer necessary to prepare reactive hypervalent iodine
compounds, and only a catalytic amount of a chiral iodoar-
ene is used as a precursor. Thus, the catalytic route provides
simpler and more efficient protocols than traditional reac-
tions based on a stoichiometric amount of the hypervalent
iodine reagent. A fundamental requirement for success in a
catalytic reaction is that direct oxidation of the substrate by
the stoichiometric co-oxidant occurs at a significantly lower
rate than its oxidation by the catalytic hypervalent iodine
species. In the case of the reaction of alkenylbenzoate sub-
strate 1, as illustrated in Scheme 2, the direct oxidation re-
action must yield by-products (e.g., Scheme 4). To date, suc-
cess in catalytic enantioselective oxidation reactions medi-
ated by chiral hypervalent iodine has been limited almost
exclusively to the α-oxidation of ketones[25] and the dearo-
matization of phenols (naphthols).[22,24] The oxidative
double cyclization of 2-(4-hydroxybut-1-enyl)benzoates is
the only current example of the catalytic enantioselective
oxidation of an alkene.[9,28] However, many research groups
have recently attained high enantioselectivity in the oxi-
Scheme 1. Synthetic routes to 4-oxyisochroman-1-ones.
The total synthesis of natural products incorporating the dation of an alkene using a stoichiometric amount of a lact-
4-hydroxyisochroman-1-one motif has attracted the atten- ate-based chiral hypervalent iodine derivative.[13,23] If the
tion of synthetic chemists, and this field has been advancing structural requirements for a successful chiral catalyst are
rapidly. Recently, the total synthesis of ajudazol B (Fig- clarified, the catalytic system may be extended to various
ure 1) was completed by Menche’s group,[10] and many re- reactions, including those that have already been reported
search groups targeting this compound have reported syn- using stoichiometric asymmetric induction.
theses of different ajudazol fragments.[12,16] The selective
formation of the 4-hydroxyisochroman-1-one core is one of
the most difficult steps in the total synthesis. Indeed, the
deoxy forms of these products have previously been synthe-
sized, which avoids the difficulties inherent in the lacton-
ization step.[17,18] In Menche’s synthetic route,[10] a highly
selective and sensitive protection and deprotection of the
vicinal hydroxy groups was required in the lactonization
step to obtain the desired hydroxyisochromanone without
the formation of the phthalide product, which is thermody-
namically more stable but undesirable.[19] The establishment
of a more reliable and efficient route to the 4-hydroxyiso-
chroman-1-one core is needed, and further research is di-
Scheme 2. Catalytic cycle involving hypervalent iodine(III).
rected towards the syntheses of this class of natural prod-
ucts and its analogs.
Recent developments in the area of asymmetric transfor-
mations induced by chiral hypervalent iodine reagents have
In this paper, a simple route to optically active 4-
contributed to powerful new strategies for stereoselective hydroxyisochroman-1-ones, biologically relevant building
oxidation.[20–25] A breakthrough in the design of a chiral blocks, is achieved by the oxylactonization of alkenylbenzo-
reagent for high stereoselectivity came with the arrival of ate with a lactate-based chiral hypervalent iodine catalyst
conformationally rigid 1,1-spiroindanone reagents[22,25d] generated in situ. This reaction system is suitable for evalu-
and
conformationally
flexible
lactate-based
rea- ating the efficiency of the catalytic cycle that includes the
gents.[9,13,23,24b,24c] The lactate-based hypervalent iodine hypervalent iodine intermediate, because the relative contri-
reagent has been used for several types of highly stereoselec- butions of the catalytic oxidation and the direct oxidation
tive oxidation since we first reported it.[23a] Oxidation reac- can be evaluated from the diastereomeric ratio of the oxi-
tions using hypervalent iodine species may operate catalyti- dation products.
Eur. J. Org. Chem. 2013, 7128–7138
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M. Shimogaki, M. Fujita, T. Sugimura
Table 1. Enantioselective acetoxylactonization of 1.[a]
FULL PAPER
Results and Discussion
Stoichiometric Oxylactonization
First, we present the results of the reaction using a stoi-
chiometric amount of a chiral hypervalent iodine reagent.
The catalytic cycle illustrated in Scheme 2 includes the oxy-
lactonization of alkenylbenzoate 1 with a hypervalent
iodine reagent as an important elementary process of the
cycle. This elementary process was performed separately
using isolated hypervalent iodine reagents (Figure 2).
Entry
Substrate
Ar*I(OAc)2
5
Yield [%]
ee [%][b]
1[c]
2
1a
1b
2
2
2
2
3
2
3
2
63
72
71
80
60
64
63
72
90
88
96
84
97
87
96
88
3
1c
4[c]
5[c]
6
1d[d]
1d
1e
Figure 2. Chiral hypervalent iodine(III) reagents.
7
8
1e
1f
First, we studied the acetoxylactonization of a series of
alkenylbenzoates 1 with a stoichiometric amount of lactate-
[a] 1 (0.10 mmol), Ar*I(OAc)2 (0.12 mmol), BF3·OEt2 (1.3 mmol),
CH2Cl2 (5 mL), acetic acid (0.3 mL). The reaction was started at
based chiral hypervalent iodine(III) reagents (Table 1). The –80 °C by the addition of BF3·OEt2. The mixture was gradually
warmed up to –40 °C over 1 h, and then quenched by the addition
acetoxylactonization was performed under reaction condi-
of water at that temperature. [b] Determined by GC analysis on a
tions similar to those reported in the preliminary ac-
chiral stationary phase. [c] The data have previously been reported
count.[13] Boron trifluoride diethyl etherate could activate
the hypervalent iodine reagent to promote immediate acet-
oxylactonization at low temperatures. The reaction selec-
tively delivered the acetoxy group onto the benzylic carbon
atom of the alkene substrate to give 4-acetoxyisochroman-
1-one 5, but without the formation of the γ-lactone product
[i.e., 3-(1-oxyalkyl)phthalide]. Various alkenylbenzoate sub-
strates were subjected to the acetoxylactonization reaction,
but Table 1 contains only those substrates selected for the
catalytic reaction described below.[29] Substrates bearing an
electron-donating substituent are not included in Table 1,
although they have been used for a key step in the synthesis
of natural products.[9] With the substrates shown in Table 1,
high levels of enantioselectivity were obtained, especially in
the reactions of substrates incorporating electron-with-
in ref.[13] [d] When the corresponding carboxylic acid substrate was
used, 5d was obtained in 84% yield with 84% ee.[13]
Scheme 3. Plausible mechanism for oxylactonization with hyperva-
lent iodine.
Acetoxylactonization product 5 was subjected to hydrol-
drawing groups such as CF3 (i.e., 1c; Table 1, entry 3). ysis to give 4-hydroxyisochroman-1-one 6, which is widely
When reagent 3, bearing two lactate groups, was used, the found as the core structure in natural products, as shown
enantioselectivity was enhanced (Table 1, entries 5 and 7).
in Figure 1. The hydrolysis was performed in aqueous meth-
In the acetoxylactonization, the cis-isochromanone prod- anol containing K2CO3 at 0 °C. Unfortunately, partial
uct (i.e., 5) was obtained from the E-substrate. In other translactonization (isomerization) into γ-lactone 7 took
words, the addition of two oxygen nucleophiles onto the place during the hydrolysis. The product ratio of 6/7 ob-
C=C double bond of the substrate proceeded with syn selec- tained depended on the electronic properties of the substit-
tivity, as can be explained by the mechanism shown in uent on the aromatic ring of the isochromanone. Unsubsti-
Scheme 3. The activated hypervalent iodine species electro- tuted compounds 5a and 5e isomerized to a small degree
philically attacked at the C=C double bond of the alkene (6a/7a = 8:2; 6e/7e = 9:1), but the presence of electron-with-
substrate, and this was followed by nucleophilic displace- drawing substituents in 5b and 5c led to greater degrees of
ments by acetate and by the internal methoxycarbonyl isomerization (6b/7b, 6c/7c = 3:7). In the latter case, re-
group. These two consecutive substitution steps proceeded arranged product 7 was already observed in the early stage
with inversion of configuration and so resulted in a syn of the hydrolysis of 5. The rearrangement to the thermody-
selectivity. Enantiopure hypervalent iodine reagents 2–4 namically more stable product (i.e., 7) may occur by hydrol-
showed good differentiation between the enantiofaces of ysis of the δ-lactone moiety. The rate of hydrolysis of the
the alkene substrate; thus these reagents must have prefer- lactone must be affected by the electronic properties of the
entially attacked the si face of the alkene substrate.
substituents on the aromatic ring; an electron-withdrawing
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Enantioselective Oxidation of Alkenylbenzoates
group enhances the rate of hydrolysis, while an electron-
The enantiomeric purity of 6 was determined by GC
donating group reduces it. In fact, selective hydrolysis with- analysis on a chiral stationary phase. At 0 °C, the product
out translactonization into the γ-lactone was achieved for a was formed with an unsatisfactory enantiomeric purity (61–
4-acetoxyisochroman-1-one with electron-donating substit- 84% ee), but enantiomerically enriched 4-hydroxyisochro-
uents on the aryl moiety during our total synthesis of natu- man-1-ones were obtained after recrystallization from ethyl
ral products.[9] The selective deacetylation of electron-with- acetate/hexane. The oxylactonization reaction using TFA
drawing isochromanones to give 6 may be difficult to proceeded even at –80 °C, but a prolonged reaction time (2–
achieve without translactonization, and so the products of 3 d) was necessary for the substrate to be consumed
acetoxylactonization cannot be counted as general precur- (Table 2, entries 3 and 10). The reaction at low temperatures
sors for the preparation of 4-hydroxyisochroman-1-ones.
gave higher enantioselectivities. The reaction of an electron-
Trifluoroacetoxylactonization may be suitable for the se- deficient substrate (i.e., 1b) at –80 °C (Table 2, entry 6)
lective preparation of 6, because the trifluoroacetoxy group barely proceeded in the presence of an increased amount of
is more readily hydrolyzed than the acetoxy group. Similarly TFA, but the enantioselectivity was moderate. The tri-
to boron trifluoride diethyl etherate, trifluoroacetic acid fluoroacetoxylactonization reaction at low temperatures
(TFA) activated the hypervalent iodine reagent to promote could be accelerated by the addition of boron trifluoride
oxylactonization and functioned as a nucleophile to give diethyl etherate in the presence of TFA (Table 2, entry 4).
trifluoroacetoxylactonization product 5Ј (Table 2). The re- The enantioselectivity (86% ee) was comparable with that
action proceeded smoothly at 0 °C. Product 5Ј was detected obtained in the acetoxylactonization reaction under similar
1
by H NMR spectroscopic analysis of the crude reaction conditions (90% ee; Table 1, entry 1). Thus, trifluoroacet-
mixture, but was too labile to purify by silica gel column oxylactonization with the chiral hypervalent iodine reagent
chromatography. Thus, isolation of the product was per- is reliable for the preparation of optically active 4-hydroxy-
formed after hydrolysis of the crude reaction mixture con- isochroman-1-ones.
taining 5Ј by treatment with potassium carbonate/meth-
anol/H2O. Notably, this hydrolysis reaction yielded 6
cleanly, even in the presence of an electron-withdrawing
group (6b/7b Ͼ 20:1, 6c/7c = 12:1).
Catalytic Oxylactonization
To simplify the oxylactonization protocol with hyperva-
lent iodine, we examined catalytic conditions in which a
catalytic amount of a chiral iodoarene was oxidized to the
hypervalent iodine species in situ using a stoichiometric co-
Table 2. Enantioselective trifluoroacetoxylactonization of 1.[a]
oxidant. It was not necessary to isolate the reactive hyper-
valent iodine compounds; only a catalytic amount of chiral
iodoarene was used as a precursor. In the stoichiometric
reaction, lactate-based hypervalent iodine reagents 2–4 gave
high enenatioselectivities. In addition to enantioselectivity,
catalytic efficiency must be taken into account in the cata-
lytic reaction. To examine the relationship between the
structure of the precatalyst and the catalytic efficiency, we
used various iodoarene precatalysts 10a–u, including achiral
compounds (Figure 3). Methyl 2-[(E)-hept-1-enyl]benzoate
Entry Substrate Ar*I(OAc)2 Time [h]
6
(1a) was selected as a benchmark substrate for the optimi-
zation of the reaction conditions, and the results are sum-
marized in Table 3.
Yield [%] ee [%][b]
1
2
1a
1a
1a
1a
1b
1b
1c
1d
1e
1e
1f
3
4
3
2
3
3
3
3
3
3
3
3.5
20
40
1
17.5
139
44
3
52
57
69
72
51
44
56
76
43
62
65
68
80
96
86
74 (94)
74
76 (99)
84 (91)
78 (99)
94
First, the reaction in the absence of an iodoarene precat-
alyst was examined as a control test (Table 3, entry 1). Sub-
strate 1a was subjected to oxidation with m-chloroperben-
zoic acid (mCPBA) in the presence of TFA in dichlorometh-
ane at 0 °C. Only the anti products (i.e., 8a and 9a) were
obtained, which suggests that these products were formed
by epoxidation followed by acid-catalyzed nucleophilic dis-
placement (Scheme 4).[30] The diastereoselectivity (anti) in
the direct oxidation with mCPBA contrasts with the syn
selectivity observed in the oxidation with hypervalent iodine
derivatives (Scheme 3). During the catalytic reaction, the di-
rect oxidation with mCPBA must occur as a background
oxidation. Ideally, the syn/anti ratio of the oxidation prod-
ucts should correspond to the ratio of the catalytic oxi-
dation to the direct oxidation. The appropriateness of this
3[c]
4[d]
5
6[c,e]
7
8
9
1
67
2.5
10[c]
11
61 (96)
[a] 1 (0.10 mmol), Ar*I(OAc)2 (0.16 mmol), CF3COOH (0.1 mL),
CH2Cl2 (4 mL), 0 °C, unless otherwise noted. [b] Determined by
GC analysis on a chiral stationary phase. The value in parentheses
corresponds to the ee value after crystallization. [c] The reaction
was carried out at –80 °C. [d] The reaction was started at –80 °C
by the addition of BF3·OEt2 (0.16 mL). The mixture was gradually
warmed up to –40 °C over 1 h, and then quenched by the addition
of water at –40 °C. [e] CF3COOH (0.4 mL).
Eur. J. Org. Chem. 2013, 7128–7138
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M. Shimogaki, M. Fujita, T. Sugimura
FULL PAPER
Figure 3. Iodoarene precatalysts.
proposal can be judged from the result of an enantioselec- Table 3, entry 15) obtained in the catalytic reaction is con-
tive catalytic reaction. A representative example of a gas sistent with that obtained in the stoichiometric oxidation
chromatogram of products of enantioselective catalytic oxi- under the corresponding reaction conditions (68% ee;
dation is shown in Figure 4. Four pairs of enantiomers of Table 2, entry 1). Thus, at least 6a must have resulted from
hydroxylactonization products 6a, 7a, 8a, and 9a were sepa- a catalytic cycle involving chiral hypervalent iodine. Essen-
rated to give eight peaks. In the chiral GC trace, anti prod- tially, the syn/anti ratio can be used as an indicator of cata-
ucts 8a and 9a were nearly racemic, whereas syn products lytic efficiency, even when an achiral iodoarene precatalyst
6a and 7a showed significant enantiomeric excesses. This is is used.
consistent with the above proposal, i.e., the direct oxidation
must yield racemic anti products, while the catalytic oxi-
dation must yield enantiocontrolled syn products. The ee
value of the minor syn product (i.e., 7a) was slightly dif-
ferent from that of the major product (i.e., 6a). This differ-
ence can be explained as being due to experimental errors
in the determination of the ee value of 7a owing to the
small amount of 7a and/or to some contribution from an
SN1 mechanism to the acid-catalyzed transformation of the
epoxide into the lactone. For 6a, the ee value (68% ee;
Figure 4. GC trace of the products of the catalytic oxidation reac-
tion of 1a with 10r at –40 °C (Table 3, entry 29); injection after
treatment with trimethylsilylimidazole, DEX-CB column at 170 °C.
6a: 92% ee, 7a: 72% ee, 8a: 0% ee, 9a: 4% ee. Ratio of the peak
areas 6a/7a/8a/9a = 80:2:14:4 agrees well with that determined by
Scheme 4. Lactonization by way of epoxidation.
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1H NMR spectroscopy (77:3:14:6).
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Enantioselective Oxidation of Alkenylbenzoates
Table 3. Hydroxylactonization of 1a under catalytic conditions.[a]
Entry
Cat.
Time [h]
Yield [%] (6a/7a/8a/9a)[b]
ee [%] of 6a[c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
–
5[d]
7
5
18
10
22
19
3
3
8
5
10.5
3
6
2
3
11
6
48.5
20.5
35
41
47
2
3
4
2.5
6
35
32
38 + 24
18.5
31
20.5
59 (0:0:76:24)
65 (47:4:35:14)
67 (54:4:29:13)
53 (38:6:40:16)
70 (20:5:51:24)
10a
10b
10c
10d
10e
10f
10g
10h
10i
[e]
(0:2:73:25)
(1:2:73:24)
[e]
80 (57:3:23:17)
68 (58:4:21:17)
60 (25:4:48:23)
72 (48:3:32:17)
68 (29:4:47:20)
60 (46:2:34:18)
63 (50:3:32:15)
67 (74:3:14:9)
50 (70:3:17:10)
43 (63:3:18:16)
70 (62:6:25:7)
51 (3:5:64:28)
55 (43:6:36:15)
59 (16:4:54:26)
53 (46:20:23:11)
76 (60:20:14:6)
79 (41:4:35:20)
73 (61:5:21:13)
79 (48:4:32:16)
70 (67:4:20:9)
70 (69:3:17:11)
46 (77:3:14:6)
64 (51:3:32:14)
71 (78:3:14:5)
30 (7:2:66:25)
51 (15:3:60:22)
48 (8:3:65:24)
10j
10k
10l
58
30
58
56
68
66
70
48
70
70
65
72
67
64
74
84
76
80
92
96
94
37
26
30
10m
10n
10n
10n
10n
10n
10n
10n
10n
10n
10o
10p
10q
10r
10r
10r
10r
10r
10s
10t
10u
16[f]
17[g]
18[h]
19[i]
20[j]
21[k]
22[l]
23[m]
24
25
26
27
28[n]
29[o]
30[n,o]
31[p]
32
33
34
[a] 1 (0.10 mmol), 10 (0.01 mmol), mCPBA (0.15 mmol), CF3COOH (0.1 mL), CH2Cl2 (4 mL), 0 °C, unless otherwise noted. The reaction
mixture was treated with K2CO3 in aqueous methanol at 0 °C for 10 min. [b] Isolated yield of a mixture of 6a, 7a, 8a, and 9a. The value
1
in parentheses is the product ratio determined by H NMR spectroscopy. [c] Determined by GC analysis on a chiral stationary phase.
[d] In CH2Cl2 (3 mL) containing CF3COOH (0.2 mL). [e] Not determined. [f] 1a was slowly added using a syringe pump over 2 h. [g] Reac-
tion carried out at –20 °C. [h] Reaction carried out in CHCl3. [i] Reaction carried out in MeCN. [j] Reaction carried out in CH2Cl2/AcOH
(9:1). [k] Reaction carried out in CH2Cl2/AcOH (1:1). [l] Co-oxidant 11 was used. [m] Co-oxidant 12 was used. [n] mCPBA was slowly
added using a syringe pump over 3.5 h (entry 28) or 11 h (entry 30). [o] Reaction carried out at –40 °C. [p] The reaction was carried out
at –80 °C for 38 h, and then at –40 °C for 24 h.
Upon the addition of a catalytic amount (10 mol-%) of ted by the ortho substituent of the iodoarene precatalyst.
iodoarene (even an achiral iodoarene 10a–10i), syn prod- In particular, the systematic change of the position of the
ucts 6a and 7a were obtained (Table 3, entries 2–10). The carbonyl group in 10e–10i provides useful insights into the
composition of the product mixtures was significantly affec- structural requirements for a catalyst (Table 3, entries 6–
Eur. J. Org. Chem. 2013, 7128–7138
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M. Shimogaki, M. Fujita, T. Sugimura
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10). The reaction catalyzed by 2,6-dimethoxy-1-iodo- precatalyst 10r significantly enhanced both the enantio-
benzene (10d) resulted in the formation of anti isomers 8a selectivity (up to 94% ee) and the syn selectivity (ca. 80%
and 9a (Table 3, entry 5) as major products. In contrast, syn) at low temperatures (Table 3, entries 29 and 31). We
when a β-oxo functional group was introduced into the 2- also examined the slow addition of substrate 1a (Table 3,
and 6-alkoxy groups in 10g and 10h, syn product 6a was entry 16) or of the mCBPA (Table 3, entries 28 and 30), but
obtained as a major isomer (Table 3, entries 8 and 9). The no significant improvement in the selectivities was ob-
product distribution was not greatly affected by the nature served.
of the β-oxo-alkoxy groups, which could be either an ester
A series of other substrates were used for the catalytic
(in 10g) or a ketone (in 10h). Notably, the oxo group at variant of hydroxylactonization, and the results are summa-
the γ-position in 10i reduced the proportion of 6a (Table 3, rized in Table 4. To further explore the combination of sub-
entry 10). Diacyloxy-substituted precatalysts 10e and 10f, strates and precatalysts, five selected precatalysts 10n–10r
which have the oxo group at the α-position, did not func- were used for the exploration of the substrate scope. Car-
tion as catalysts for the formation of syn products (Table 3, boxylic acid substrate 1Јa also gave hydroxylactonization
entries 6 and 7). These results suggest that the β-oxo group products 6a–9a, but its enantioselectivity and syn/anti ratio
in the ortho-alkoxy side-chain is important for successful decreased slightly (Table 4, entry 1) compared with methyl
catalytic design. The chiral lactate-based catalyst has the ester substrate 1a (Table 3, entry 15). The introduction of
same structural features as the β-oxo-alkoxy design, so this an electron-withdrawing substituent (5-Br for 1b and 4-CF3
must result in enhancements of both the catalytic efficiency for 1c) onto the aryl group of the substrate was also toler-
and the enantioselectivity.
ated, but it resulted in a diminished reaction rate (Table 4,
Several derivatives of lactate-based iodoarenes (i.e., 10j– entries 2–10). Pleasingly, for enantioselective induction at
10u) were used for the catalytic hydroxylactonization of 1a 0 °C, the electron-withdrawing substituents in 1b and 1c
(Table 3, entries 11–34). First, a substituent was introduced seemed to be slightly preferred (Table 4, entries 2–6, 8, and
at the ortho position into the simple lactate-based iodoarene 10) over the standard substrate 1a, but disappointingly, the
10j, and the electronic and steric effects were examined reaction at low temperatures resulted in a decrease in
(Table 3, entries 11–15, 10j–10n). Precatalyst 10n, which has enantioselectivity (Table 4, entries 7 and 9). Variation of the
two lactate groups, resulted in the highest enantioselectivity alkenyl side-chain of the substrate was examined (in 1d and
and syn selectivity of all of the precatalysts 10j–10n. Alter- 1e). The reactions of 1d and 1e at 0 °C (Table 4, entries 11,
native solvents (Table 3, entries 18–21) and co-oxidants 13–16, 18, 20, and 21) led to higher enantioselectivities than
(Table 3, entries 22 and 23) were explored using 10n, but that obtained with 1a under the same reaction conditions,
the standard conditions (dichloromethane solvent contain- but they resulted in moderate syn/anti ratios. Relatively
ing mCPBA co-oxidant) were found to be optimal. A low good results in terms of both enantioselectivity and syn/anti
enantioselectivity in chloroform solvent (Table 3, entry 18) selectivity were obtained when menthyl derivative 10r was
and a low yield of the syn product in acetonitrile solvent used as precatalyst (Table 4, entries 16 and 21). The slow
(Table 3, entry 19) were obtained. When cyclic peroxides 11 addition of mCBPA led to a slight improvement in the
and 12[31] were used instead of mCPBA (Table 3, entries 22 syn/anti selectivity (Table 4, entries 6 and 22). Pleasingly, the
and 23), prolonged reaction times were required (41 h and reactions of substrates 1d and 1e at low temperatures led to
47 h at 0 °C) for the consumption of the starting material. enhancements of both the enantioselectivity and the
Furthermore, direct oxidation by the cyclic peroxides may syn/anti selectivity to ca. 90% ee and ca. 80% syn (Table 4,
have formed the minor syn γ-lactone product (i.e., 7a) to- entries 12, 17, 19, 23, and 24).
gether with the anti products, because the ee value of 7a
was very low (8% ee).
Although further enhancement of the catalytic efficiency
is required, the catalytic variant of the oxidation of ortho-
Next, based on the structure of 10n, we examined the alk-1-enylbenzoates successfully competed with direct oxi-
effect of the substituent on the aryl group (10o and 10p; dation by mCPBA to give high levels of enantioselectivity
Table 3, entries 24 and 25) and also the effect of structural (ca. 90% ee). This investigation provides a synthetically at-
variation of the lactate moiety (10q and 10r; Table 3, en- tractive methodology for the preparation of 4-hydroxy-
tries 26 and 27). Isopropyl derivative 10q gave a high isochroman-1-one natural products and related compounds.
enantioselectivity (84% ee), but the amount of syn products Furthermore, the reaction system seems to be useful for the
formed was low (Table 3, entry 26). When the sterically con- evaluation of the catalytic efficiency of organocatalytic oxi-
gested menthyl group was introduced as the ester of the dations mediated by hypervalent iodine.
lactate group (10r), a relatively favorable result was ob-
Finally, we would like to discuss the enantioselective
tained, in terms of both enantioselectivity and syn/anti ratio catalytic cycle from a mechanistic viewpoint. The enantiose-
(Table 3, entry 27). The use of amide derivatives 10s–10u as lective catalytic cycle includes the enantioselective oxidation
precatalysts resulted in significantly reduced enantio- of alkenylbenzoate substrates 1 by chiral hypervalent iodine
selectivities and syn/anti ratios (Table 3, entries 32–34). We species. In other words, the enantioselectivity in the cata-
then evaluated the influence of the reaction temperature lytic reaction can be compared with that in the stoichiomet-
using 10n and 10r as precatalysts (Table 3, entries 17, 29, ric oxidation. The enantioselectivities observed in the stoi-
and 31). The reaction with 10n at –20 °C led to a slight chiometric oxidations (Table 2) are consistent with those
increase in the enantioselectivity (Table 3, entry 17), and obtained in the catalytic reactions (Tables 3 and 4). This
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Eur. J. Org. Chem. 2013, 7128–7138

Enantioselective Oxidation of Alkenylbenzoates
Table 4. Other substrates in the catalytic hydroxylactonization.[a]
Entry
Subst.
Cat.
Time [h]
Yield [%] (6/7/8/9)[b]
ee[%] of 6[c]
1
2
3
4
1Јa[d]
1b
1b
1b
1b
1b
1b
1c
1c
1c
1d
1d
1d
1d
1d
1d
1d
1e
1e
1e
1e
1e
1e
1e
1f
10n
10n
10o
10p
10r
10r
10r
10n
10n
10o
10n
10n
10o
10p
10q
10r
10r
10n
10n
10p
10r
10r
10r
10r
10n
1
5
15
4.5
5
10
83
24
2 + 17
19
13.5
20
10
17.5
33
15
69
17.5
24
18
5
8
56 (56:1:25:18)
75 (59:15:17:9)
67 (57:6:17:20)
77 (39:15:30:16)
81 (61:9:17:13)
65 (69:4:11:16)
79 (82:0:9:9)
64
78
76
80
74
74
58
82
67
72
84
90
82
68
89
82
88
82
80
78
86
88
88
98
62
5
6[e]
7[f,g]
8
67 (56:4:21:19)
53 (55:5:10:30)
45 (46:13:18:23)
56 (64:18:16:2)
49 (70:4:25:1)
47 (59:17:23:1)
42 (29:5:59:7)
61 (56:10:30:4)
61 (74:12:13:1)
70 (76:8:16:0)
66 (41:2:45:12)
66 (68:2:22:8)
33 (54:4:28:14)
59 (54:4:33:9)
59 (66:2:23:9)
60 (65:3:26:6)
53 (76:1:22:1)
56 (54:5:23:18)
9[h]
10
11
12[f]
13
14
15
16
17[f]
18
19[i]
20
21
22[e]
23[i]
24[g,j]
25
13
65 + 21
4
[a] 1 (0.10 mmol), 10 (0.01 mmol), mCPBA (0.15 mmol), CF3COOH (0.1 mL), CH2Cl2 (4 mL), 0 °C, unless otherwise noted. The reaction
mixture was treated with K2CO3 in aqueous methanol at 0 °C. [b] Isolated yield of a mixture of 6, 7, 8, and 9. The value in parentheses
1
is the product ratio determined by H NMR spectroscopy. [c] Determined by GC analysis on a chiral stationary phase. [d] The substrate
was 2-[(E)-hept-1-enyl]benzoic acid (1Јa). [e] mCPBA was slowly added using a syringe pump over 5 h (entry 6) or 3 h (entry 22). [f] Reac-
tion carried out at –40 °C. [g] CF3COOH (0.3 mL). [h] The reaction was carried out in the presence of BF3·OEt2 (0.1 mL) and CF3COOH
(0.3 mL) at –80 °C for 2 h, and then at –40 °C for 17 h. [i] Reaction carried out at –20 °C. [j] The reaction was carried out at –80 °C for
65 h, and then at –40 °C for 21 h.
indicates that the presence of mCPBA and its reduced form iodoarenes was fixed at 10 mol-%, and the amount of 10n
does not affect the enantioselectivity. Thus, the enantio- was decreased. The ee value of the major syn product (i.e.,
selectivity in the catalytic reaction can be discussed along 6a) decreased as the amount of 10n in the mixed precata-
the lines of the stoichiometric oxidation mechanism.
lysts decreased (open circles), whereas the ee value of 6a
Apart from the enantioselectivity, the catalytic efficiency remained constant (68% ee) when the amount of 10n added
is an important issue in the catalytic cycle. The lactate moie- was decreased without the addition of achiral 10d (filled
ties of 10n seem to enhance the catalytic efficiency com- circles). Achiral 10d worked as a precatalyst to give racemic
pared with 10d (Table 3, entries 5 and 15), as mentioned 6a and resulted in a decrease in the ee value. The results in
above. To confirm the effect of the lactate groups, the fol- Figure 5 indicate that these two precatalysts have different
lowing control experiments were conducted. A mixture of catalytic efficiencies. If the two precatalysts 10n and 10d had
10n and 10d was used as a precatalyst for the oxidation of had the same catalytic efficiency, the ee value would have
1a, as shown in Figure 5.[32] The total amount of these two decreased linearly to half of 68% at 5 mol-% 10n and 5 mol-
Eur. J. Org. Chem. 2013, 7128–7138
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7135

M. Shimogaki, M. Fujita, T. Sugimura
FULL PAPER
% 10d. The actual ee value is above the line. This is consis- unidentified signals were observed together with the genera-
tent with the independent experimental results (i.e., Table 3, tion of dimethoxyiodobenzene 10d. The same unidentified
entries 5 and 15), and indicates that 10n is more efficient signals were also observed during the oxidation of 10d with
than 10d.
mCPBA (Figure S1). An activated hypervalent iodine com-
pound is known to react electrophilically with an electron-
donating arene to give a diaryliodonium compound.[34]
Such compounds could reasonably be assumed to be the
by-products observed in the NMR measurements.[35] Such
a decomposition of precatalyst 10d may cause the decrease
in catalytic efficiency. The lactate moiety in precatalyst 10n
may partially stabilize the activated hypervalent species by
coordination of the lactate moiety to the electron-deficient
iodine atom,[13] and thus 10n is more tolerant to decomposi-
tion and can maintain its catalytic efficiency. The difference
in the catalytic efficiencies of achiral precatalysts 10g and
10i (Table 3, entries 8 and 10) can be explained by the con-
tribution of the coordination of the ester group.
Figure 5. Dependence of the enantiomeric excess of 6a on the
amount of precatalyst 10n. The reaction conditions were the same
as those in Table 3. Either only 10n was used as the precatalyst
(filled circles), or chiral 10n and achiral 10d were mixed; 10n + 10d
= 10 mol-% (open circles).
Conclusions
A concise route to optically active 3-alkyl-4-hydroxy-
isochroman-1-ones has been established using the enantio-
selective oxylactonization of an ortho-alkenylbenzoate me-
diated by a catalytic amount of a chiral lactate-based hyper-
valent iodine(III) species generated in situ. On the basis of
the results presented in this paper, it is reasonable to suggest
that the lactate moiety plays an important role in the en-
hancement of the catalytic efficiency as well as that of the
enantioselectivity. These results should provide a basis for
the synthesis of many 4-hydroxyisochoman-1-one natural
products and their analogs, and also for further develop-
ments in the field of highly selective oxidation mediated by
hypervalent iodine species.
It is interesting to consider why lactate-based precatalyst
10n has a higher efficiency than dimethoxy derivative 10d.
To gain a mechanistic insight into the catalytic efficiency,
the course of the oxidation was monitored by 1H NMR
spectroscopy. The catalytic cycle consists of two oxidation
steps: 1) oxidation of iodoarene 10 with mCPBA to give the
corresponding hypervalent iodine(III) species; and 2) oxi-
dation of the substrate with the generated hypervalent io-
dine(III) species. These two elementary processes were ex-
amined independently.
First, oxidations of iodoarenes 10d and 10n with
mCPBA[33] were performed in CD2Cl2 containing TFA in
an NMR tube. The time-dependent changes of the concen-
trations of the iodoarene and the corresponding hyperva-
lent iodine compound are shown in Figures S1–S3 (Sup-
porting Information). Iodoarenes 10d and 10n were readily
oxidized within 10–20 min at room temperature, and their
rates of oxidation were similar. On balance, the oxidation
of the dimethoxyiodobenzene 10d seemed to be slightly
faster than that of the lactate-based 10n. Thus, the high
efficiency of the catalytic oxidation mediated by 10n cannot
be explained by a difference in the kinetics of the first ele-
mentary process.
As the second elementary process, the oxidation of sub-
strate 1a was examined. Isolated hypervalent iodine(III)
compounds were used for stoichiometric reactions in an
NMR tube (Figures S4 and S5 in the Supporting Infor-
mation). The oxidation with lactate-based hypervalent rea-
gent 3 proceeded cleanly in approximately 1 h to give oxy-
isochromanone product 5Јa and the corresponding iodoar-
ene (i.e., 10n), as shown in Figure S5. The oxidation with 2-
(diacetoxyiodo)-1,3-dimethoxybenzene (13) also led to the
formation of 5Јa at a similar reaction rate (Figure S4).
Thus, the kinetics of the second elementary process do not
seem to be a major reason for the difference in the catalytic
Experimental Section
General Procedure for Acetoxylactonization: A dichloromethane
solution (5 mL) containing
1
(0.10 mmol), Ar*I(OAc)2
(0.12 mmol), and acetic acid (0.3 mL) under nitrogen was cooled
to –80 °C using an EYELA PSL-1800 low-temperature bath with a
magnetic stirrer. Boron trifluoride diethyl etherate (1.3 mmol) was
added to the solution at –80 °C. The solution was gradually
warmed up to –40 °C over 1 h. The reaction mixture was then
quenched by the addition of water, and the mixture was extracted
with dichloromethane. The organic phase was dried with Na2SO4
and concentrated in vacuo. The crude mixture was purified by col-
umn chromatography (SiO2, eluent: ethyl acetate in hexane). The
enantiomeric ratio of the product was determined by gas
chromatography using a chiral column (Chirasil-DEX-CB or Sup-
elco β-DEX-325).
General Procedure for Trifluoroacetoxy-lactonization:
A di-
chloromethane solution (4 mL) containing 1 (0.10 mmol) and
Ar*I(OAc)2 (0.16 mmol) under nitrogen was cooled to 0 °C. Tri-
fluoroacetic acid (0.1 mL) was added to the solution at 0 °C, and
the mixture was stirred at 0 °C for 1–44 h. The reaction was moni-
tored by TLC. After the starting material had been consumed, the
reaction mixture was quenched by the addition of NaHCO3 (aq.),
and the mixture was extracted with dichloromethane. The organic
efficiency. Notably, in the oxidation of 1a by 13 (Figure S4), phase was dried with Na2SO4 and concentrated in vacuo. The
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Enantioselective Oxidation of Alkenylbenzoates
1
[12]
a) S. J. Hobson, A. Parkin, R. Marquez, Org. Lett. 2008, 10,
2813–2816; b) B. A. Egan, M. Paradowski, L. H. Thomas, R.
Marquez, Org. Lett. 2011, 13, 2086–2089; c) B. A. Egan, M.
Paradowski, L. H. Thomas, R. Marquez, Tetrahedron 2011, 67,
9700–9707.
M. Fujita, Y. Yoshida, K. Miyata, A. Wakisaka, T. Sugimura,
Angew. Chem. 2010, 122, 7222–7225; Angew. Chem. Int. Ed.
2010, 49, 7068–7071.
crude mixture was analyzed by H NMR spectroscopy, then it was
hydrolyzed in aqueous methanol in the presence of K2CO3 at 0 °C.
The hydrolyzed products were extracted with dichloromethane and
purified by column chromatography (SiO2, eluent: ethyl acetate in
hexane). The enantiomeric ratio of the product was determined by
gas chromatography using a chiral column (Chirasil-DEX-CB or
Supelco β-DEX-325).
[13]
[14]
a) G. Berti, J. Org. Chem. 1959, 24, 934–938, and references
cited herein; b) R. Annunziata, M. Cinquini, F. Cozzi, P. Gia-
roni, M. Benaglia, Tetrahedron 1991, 47, 5737–5758; c) M.-P.
Denieul, B. Laursen, R. Hazell, T. Skrystrup, J. Org. Chem.
2000, 65, 6052–6060; d) T. Ohzeki, K. Mori, Biosci. Biotechnol.
Biochem. 2003, 67, 2240–2244; e) I. F. Cottrell, A. R. Cowley,
L. J. Croft, L. Hymns, M. G. Moloney, E. J. Nettleton, H. K.
Smithies, A. L. Thompson, Tetrahedron 2009, 65, 2537–2550;
f) R. S. Reddy, I. N. C. Kiran, A. Sudalai, Org. Biomol. Chem.
2012, 10, 3655–3661; g) D. C. Babu, Ch. B. Rao, D. Ramesh,
S. R. Swamy, Y. Venkateswarlu, Tetrahedron Lett. 2012, 53,
3633–3636; T.-Y. Yuen, M. A. Brimble, Org. Lett. 2012, 14,
5154–5157.
The oxidative lactonization of aryl-substituted substrates such
as 2-(2-phenylethenyl)benzoic acid gave isochromanone prod-
ucts. The endo- vs. exo-selectivity may have been controlled by
the electron-donating aryl substituent, see: a) G. Berti, Tetrahe-
dron 1958, 4, 393–402; b) D. L. J. Clive, C. G. Russel, G. Chit-
tattu, A. Singh, Tetrahedron 1980, 36, 1399–1408; c) T. Izumi,
N. Morishita, J. Heterocycl. Chem. 1994, 31, 145–152; d) S. A.
Shahzad, C. Venin, T. Wirth, Eur. J. Org. Chem. 2010, 3465–
3472; e) J. Chen, L. Zhou, C. K. Tan, Y.-Y. Yeung, J. Org.
Chem. 2012, 77, 999–1009.
General Procedure for Catalytic Oxy-lactonization: A dichloro-
methane solution (4 mL) containing 1 (0.10 mmol), m-chloroper-
benzoic acid (0.15 mmol), and 10 (0.010 mmol) under nitrogen was
cooled to 0 °C. Trifluoroacetic acid (0.1 mL) was added to the solu-
tion at 0 °C, and the mixture was stirred at 0 °C for 2–47 h. The
reaction was monitored by TLC. After the starting material had
been consumed, the reaction mixture was quenched by the addition
of NaHCO3 (aq.), and the mixture was extracted with dichloro-
methane. The organic phase was dried with Na2SO4 and concen-
trated in vacuo. The crude mixture was analyzed by 1H NMR spec-
troscopy, and then it was hydrolyzed in aqueous methanol in the
presence of K2CO3 at 0 °C. The hydrolyzed products were extracted
with dichloromethane and purified by column chromatography
(SiO2, eluent: ethyl acetate in hexane). The enantiomeric ratio of
the product was determined by gas chromatography using a chiral
column (Chirasil-DEX-CB or Supelco β-DEX-325).
[15]
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization data for new com-
pounds, and additional data.
[16]
[17]
a) O. Krebs, R. J. K. Taylor, Org. Lett. 2005, 7, 1063–1066; b)
D. Ganame, T. Quach, C. Poole, M. Rizzacasa, Tetrahedron
Lett. 2007, 48, 5841–5843.
a) S. Birkett, D. Ganame, B. C. Hawkins, S. Meiries, T. Quach,
M. A. Rizzacasa, Org. Lett. 2011, 13, 1964–1967; b) S. Birkett,
D. Ganame, B. C. Hawkins, S. Meiries, T. Quach, M. A. Rizza-
casa, J. Org. Chem. 2013, 78, 116–123.
Acknowledgments
This research was partially supported by the Japan Society for the
Promotion of Science (JSPS) through a Grant-in-Aid for Scientific
Research (C) (23550059).
[18]
a) X. Jiang, J. García-Fortanet, J. K. De Brabander, J. Am.
Chem. Soc. 2005, 127, 11254–11255; b) X. Huang, N. Shao, A.
Palani, R. Aslanian, A. Buevich, Org. Lett. 2007, 9, 2597–2600;
c) Y. Feng, X. Jiang, J. K. De Brabander, J. Am. Chem. Soc.
2012, 134, 17083–17093; d) T. N. Trotter, A. M. M. Albury,
M. P. Jennings, J. Org. Chem. 2012, 77, 7688–7692; e) P. J.
Reddy, A. S. Reddy, J. S. Yadav, B. V. S. Reddy, Tetrahedron
Lett. 2012, 53, 4051–4053; f) J. Barbier, R. Jansen, H. Irschik,
S. Benson, K. Gerth, B. Böhlendorf, G. Höfle, H. Reichenbach,
J. Wegner, C. Zeilinger, A. Kirschning, R. Müller, Angew.
Chem. 2012, 124, 1282–1286; Angew. Chem. Int. Ed. 2012, 51,
1256–1260; g) T.-S. Zhu, J.-P. Chen, M.-H. Xu, Chem. Eur. J.
2013, 19, 865–869.
[1] a) D. C. Aldridge, S. Galt, D. Giles, W. B. Turner, J. Chem. Soc.
C 1971, 1623–1627; b) M. J. Garson, J. Staunton, P. G. Jones,
J. Chem. Soc. Perkin Trans. 1 1984, 1021–1026.
[2] S. Suzuki, T. Murayama, Y. Shiono, Phytochemistry 2005, 66,
2329–2333.
[3] a) W. Zhang, K. Krohn, S. Draeger, B. Schulz, J. Nat. Prod.
2008, 71, 1078–1081; b) K. Tianpanich, S. Prachya, S. Wiyak-
rutta, C. Mahidol, S. Ruchirawat, P. Kittakoop, J. Nat. Prod.
2011, 74, 79–81.
[4] R. Jansen, B. Kunze, H. Reichenbach, G. Hofle, Eur. J. Org.
Chem. 2002, 917–921.
[5] a) M. Isaka, A. Yangchum, S. Intamas, K. Kocharin, E. B. G.
Jones, P. Kongsaeree, S. Prabpai, Tetrahedron 2009, 65, 4396–
4403; b) L. Xu, J. Xue, X. Wei, Z. He, X. Chen, J. Nat. Prod.
2010, 73, 885–889.
[6] G. Nonaka, T. Sakai, K. Mihashi, I. Nishioka, Chem. Pharm.
Bull. 1991, 39, 884–888.
[7] M. Taniguchi, M. Yanai, Y. Q. Xiao, T. Kido, K. Baba, Phyto-
chemistry 1996, 42, 843–846.
[8] a) D. Deffieux, A. Natangelo, G. Malik, L. Pouységu, J.
Charris, S. Quideau, Chem. Commun. 2011, 47, 1628–1630; b)
L. Pouységu, D. Deffieux, G. Malik, A. Natangelo, S. Quideau,
Nat. Prod. Rep. 2011, 28, 853–874.
[9] a) M. Fujita, K. Mori, M. Shimogaki, T. Sugimura, Org. Lett.
2012, 14, 1294–1297; b) M. Fujita, K. Mori, M. Shimogaki, T.
Sugimura, RSC Adv. 2013, DOI: 10.1039/C3RA43230K.
[10] S. Essig, S. Bretzke, R. Müller, D. Menche, J. Am. Chem. Soc.
2012, 134, 19362–19365.
[11] M. F. Hentemann, J. G. Allen, S. J. Danishefsky, Angew. Chem.
2000, 112, 2013–2016; Angew. Chem. Int. Ed. 2000, 39, 1937–
1940.
[19]
[20]
For related papers, see: a) A. N. Phung, M. T. Zannetti, G.
Whited, W.-D. Fessner, Angew. Chem. 2003, 115, 4970–4972;
Angew. Chem. Int. Ed. 2003, 42, 4821–4824; b) D. C. Babu,
C. B. Rao, D. Ramesh, S. R. Swamy, Y. Venkateswarlu, Tetra-
hedron Lett. 2012, 53, 3633–3636.
For recent highlights on asymmetric oxidation with chiral
hypervalent iodine, see: a) M. Ngatimin, D. W. Lupton, Aust. J.
Chem. 2010, 63, 653–658; b) H. Liang, M. A. Ciufolini, Angew.
Chem. 2011, 123, 12051–12053; Angew. Chem. Int. Ed. 2011,
50, 11849–11851; c) M. Uyanik, K. Ishihara, J. Synth. Org.
Chem. Jpn. 2012, 70, 1116–1121; d) M. J. Rawling, N. C. O.
Tomkinson, Org. Biomol. Chem. 2013, 11, 1434–1440; e) U.
Farid, T. Wirth, in: Asymmetric Synthesis II (Eds.: M.
Christmann, S. Bräse), Wiley-VCH, Weinheim, Germany, 2012,
p. 197–203.
[21]
For selected examples, see: a) T. Imamoto, H. Koto, Chem.
Lett. 1986, 967–968; b) D. G. Ray III, G. F. Koser, J. Am.
Chem. Soc. 1990, 112, 5672–5673; c) U. H. Hirt, B. Spingler, T.
Wirth, J. Org. Chem. 1998, 63, 7674–7679; d) H. Tohma, S.
Eur. J. Org. Chem. 2013, 7128–7138
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7137

M. Shimogaki, M. Fujita, T. Sugimura
FULL PAPER
Takizawa, H. Watanabe, Y. Fukuoka, T. Maegawa, Y. Kita, J.
Org. Chem. 1999, 64, 3519–3523; e) M. Ochiai, Y. Kitagawa,
N. Takayama, Y. Takaoka, M. Shiro, J. Am. Chem. Soc. 1999,
121, 9233–9234; f) U. Ladziata, J. Carlson, V. V. Zhdankin, Tet-
rahedron Lett. 2006, 47, 6301–6304; g) J. K. Boppisetti, V. B.
Birman, Org. Lett. 2009, 11, 1221–1223; h) S. J. Murray, H.
Müller-Bunz, H. Ibrahim, Chem. Commun. 2012, 48, 6268–
6270.
4512; Angew. Chem. Int. Ed. 2006, 45, 4402–4404; b) M. Och-
iai, Chem. Rec. 2007, 7, 12–23; c) M. Ochiai, K. Miyamoto,
Eur. J. Org. Chem. 2008, 4229–4239; d) T. Dohi, Y. Kita, Chem.
Commun. 2009, 2073–2085.
a) M. Ochiai, Y. Takeuchi, T. Katayama, T. Sueda, K. Miyam-
oto, J. Am. Chem. Soc. 2005, 127, 12244–12245; b) T. Dohi, A.
Maruyama, M. Yoshimura, K. Morimoto, H. Tohma, Y. Kita,
Angew. Chem. 2005, 117, 6349–6352; Angew. Chem. Int. Ed.
2005, 44, 6193–6196; c) K. Miyamoto, Y. Sakai, S. Goda, M.
Ochiai, Chem. Commun. 2012, 48, 982–984.
Achiral iodoarnes have been used for the oxidation of alkenes,
see: a) K. Miyamoto, Y. Sei, K. Yamaguchi, M. Ochiai, J. Am.
Chem. Soc. 2009, 131, 1382–1383; b) J. Yan, H. Wang, Z. Yang,
Y. H e, Synlett 2009, 2669–2672; c) Z.-S. Zhou, X.-H. He, Tetra-
hedron Lett. 2010, 51, 2480–2482; d) A. Kong, S. B. Blakey,
Synthesis 2012, 44, 1190–1198; e) W. Zhong, S. Liu, J. Yang,
X. Meng, Z. Li, Org. Lett. 2012, 14, 3336–3339.
For the determination of the enantiomeric ratio of the products
obtained in the catalytic oxylactonization, we had difficulty
identifying appropriate conditions for the chromatographic
separation because a mixture of four products, 6, 7, 8, and 9,
was formed, each as a pair of enantiomers. To determine the
ee value of 6, the enantiomers of 6 must be separated, and the
two peaks must not overlap with those arising from the other
isomers.
[27]
[28]
[22] a) T. Dohi, A. Maruyama, N. Takenaga, K. Senami, Y. Mina-
mitsuji, H. Fujioka, S. B. Caemmerer, Y. Kita, Angew. Chem.
2008, 120, 3847–3850; Angew. Chem. Int. Ed. 2008, 47, 3787–
3790; b) T. Dohi, N. Takenaga, T. Nakae, Y. Toyoda, M. Yama-
saki, M. Shiro, H. Fujioka, A. Maruyama, Y. Kita, J. Am.
Chem. Soc. 2013, 135, 4558–4566.
[23] a) M. Fujita, S. Okuno, H. J. Lee, T. Sugimura, T. Okuyama,
Tetrahedron Lett. 2007, 48, 8691–8694; b) M. Fujita, Y.
Ookubo, T. Sugimura, Tetrahedron Lett. 2009, 50, 1298–1300;
c) M. Fujita, M. Wakita, T. Sugimura, Chem. Commun. 2011,
47, 3983–3985; d) C. Röben, J. A. Souto, Y. González, A. Lish-
chynskyi, K. Muñiz, Angew. Chem. 2011, 123, 9650–9654; An-
gew. Chem. Int. Ed. 2011, 50, 9478–9482; e) U. Farid, T. Wirth,
Angew. Chem. 2012, 124, 3518–3522; Angew. Chem. Int. Ed.
2012, 51, 3462–3465; f) W. Kong, P. Feige, T. de Haro, C. Nev-
ado, Angew. Chem. 2013, 125, 2529–2533; Angew. Chem. Int.
Ed. 2013, 52, 2469–2473; g) U. Farid, F. Malmedy, R. Claveau,
L. Albers, T. Wirth, Angew. Chem. 2013, 125, 7156–7160; An-
gew. Chem. Int. Ed. 2013, 52, 7018–7022.
[24] a) S. Quideau, G. Lyvinec, M. Marguerit, K. Bathany, A. Oz-
anne-Beaudenon, T. Buffeteau, D. Cavagnat, A. Chénedé, An-
gew. Chem. 2009, 121, 4675–4679; Angew. Chem. Int. Ed. 2009,
48, 4605–4609; b) M. Uyanik, T. Yasui, K. Ishihara, Angew.
Chem. 2010, 122, 2221–2223; Angew. Chem. Int. Ed. 2010, 49,
2175–2177; c) M. Uyanik, T. Yasui, K. Ishihara, Tetrahedron
2011, 66, 5841–5851; d) K. A. Volp, A. M. Harned, Chem.
Commun. 2013, 49, 3001–3003.
[29]
[30]
[31]
For the TFA-catalyzed lactonization of an epoxide, see: R. M.
Cory, B. M. Ritchie, A. M. Shrier, Tetrahedron Lett. 1990, 31,
6789–6792.
a) J. C. Griffith, K. M. Jones, S. Picon, M. J. Rawling, B. M.
Kariuki, M. Campbell, N. C. O. Tomkinson, J. Am. Chem. Soc.
2010, 132, 14409–14411; b) K. M. Jones, N. C. O. Tomkinson,
J. Org. Chem. 2012, 77, 921–928; c) S. Picon, M. Rawling, M.
Campbell, N. C. O. Tomkinson, Org. Lett. 2012, 14, 6250–
6253.
[25] a) R. D. Richardson, T. K. Page, S. Altermann, S. M. Paradine,
A. N. French, T. Wirth, Synlett 2007, 538–542; b) S. M. Al-
termann, R. D. Richardson, T. K. Page, R. K. Schmidt, E.
Holland, U. Mohammed, S. M. Paradine, A. N. French, C.
Richter, A. M. Bahar, B. Witulski, T. Wirth, Eur. J. Org. Chem.
2008, 5315–5328; c) U. Farooq, S. Schäfer, A. A. Shah, D. M.
Freudendahl, T. Wirth, Synthesis 2010, 1023–1029; d) J. Yu, J.
Cui, X.-S. Hou, S.-S. Liu, W.-C. Gao, S. Jiang, J. Tian, C.
Zhang, Tetrahedron: Asymmetry 2011, 22, 2039–2055; e) A.-A.
Guilbault, C. Y. Legault, ACS Catal. 2012, 2, 219–222; f) A.
Rodríguez, W. J. Moran, Synthesis 2012, 44, 1178–1182; g) A.-
A. Guilbault, B. Basdevant, V. Wanie, C. Y. Legault, J. Org.
Chem. 2012, 77, 11283–11295.
[32] Details are summarized in Table S1 in the Supporting Infor-
mation.
[33] M. Iinuma, K. Moriyama, H. Togo, Synlett 2012, 23, 2663–
2666.
[34] T. Kitamura, J. Matsuyuki, H. Taniguchi, Synthesis 1994, 147–
148.
[35] The same 1H NMR signals were also observed during the reac-
tion of 2-iodo-1,3-dimethoxybenzene (10d) with 2-(diacetoxy-
iodo)-1,3-dimethoxybenzene (13) in the presence of TFA (Fig-
ure S6). The reaction mixture was subjected to electrospray
ionization mass spectrometric analysis; the signal observed at
m/z = 527 is consistent with the formation of the corresponding
diaryliodonium ion.
[26] For a highlight on the catalytic use of hypervalent iodine, see:
a) R. D. Richardson, T. Wirth, Angew. Chem. 2006, 118, 4510–
Received: June 28, 2013
Published Online: September 17, 2013
7138
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Eur. J. Org. Chem. 2013, 7128–7138