Oxidative rearrangement of flavanones with thallium(III) nitrate, lead tetraacetate and hypervalent iodines in trimethyl orthoformate and perchloric or sulfuric acid

Article abstract of DOI:10.5560/ZNB.2012-0214

An HPLC monitoring protocol has been developed to follow the reaction of flavanone [(±)-1] with thallium(III) nitrate, lead tetracetate, phenyliodonium diacetate (PIDA) or [hydroxyl(tosyloxy)iodo]benzene in trimethyl orthoformate. Besides the major ring-c

Full text of DOI:10.5560/ZNB.2012-0214

Oxidative Rearrangement of Flavanones with Thallium(III) Nitrate,
Lead Tetraacetate and Hypervalent Iodines in Trimethyl Orthoformate
and Perchloric or Sulfuric Acid
a
a
a
a
Istv a´ n N e´ meth , Attila Kiss-Szikszai , T u¨ nde Zita Illy e´ s , Attila M a´ ndi ,
b
a
a
Istv a´ n Kom a´ romi , Tibor Kurt a´ n , and S a´ ndor Antus
a
Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary
Vascular Biology, Thrombosis and Hemostasis Research Group, Hungarian Academy of
Sciences, University of Debrecen, H-4032 Debrecen, Hungary
b
Reprint requests to Prof. Dr. S a´ ndor Antus. Fax: +36-52-512-744.
E-mail: antus.sandor@science.unideb.hu
Z. Naturforsch. 2012, 67b, 1289 – 1296 / DOI: 10.5560/ZNB.2012-0214
Received August 2, 2012
´
In memory of Professor Andr a´ s Lipt a´ k
An HPLC monitoring protocol has been developed to follow the reaction of flavanone
[
(±)-1] with thallium(III) nitrate, lead tetracetate, phenyliodonium diacetate (PIDA) or [hy-
droxyl(tosyloxy)iodo]benzene in trimethyl orthoformate. Besides the major ring-contraction prod-
uct, the 2,3-dihydrobenzo[b]furan derivative (±)-4a, minor components were also identified, and
their structures including the relative stereochemistry and a plausible mechanism of formation are
reported and compared with literature data. The oxidation reactions were monitored by HPLC at dif-
ferent conditions, and the structure and the ratio of the products were determined and compared. The
preferred formation of flavone (5) from (±)-flavanone (1) by PIDA is explained by quantum-chemical
calculations on the intermediate formed by the addition of this reagent to the enol ether derivative of
(
±)-1.
Key words: Flavanones, Ring-contraction, Thallium(III) Nitrate, Lead Tetraacetate, Hypervalent
Iodine
Introduction
amount of sulfuric acid affording a higher yield (85%)
was published by Khanne [2]. The cis stereochemistry
1
The oxidative rearrangement of flavanone deriva- of the product was determined by the HNMR data of
tives induced by thallium(III) nitrate (TTN·3H O), the carboxylic acid derivative (±)-4c [δ = 6.05 ppm, d,
2
lead tetraacetate (LTA) or phenyliodonium diacetate 1H, 2-H, J = 8.5 Hz)] obtained by the alkaline hydrol-
(
PIDA) is considered a possible route for the prepa- ysis of (±)-4b.
ration of 2,3-dihydro-2-arylbenzo[b]furans. In 1993, Moreover, a plausible mechanism of this transfor-
Kapoor et al. reported [1] that the oxidative rearrange- mation was also proposed (Scheme 1), the key inter-
ment of racemic flavanone [(±)-1] by TTN·3H O in mediate of which was supposed to be 3a possessing
2
trimethyl orthoformate (TMOF) in the presence of a lead(IV) atom at C-3 formed from racemic flavanone
a catalytic amount of 70% perchloric acid resulted in [(±)-1] via enol ether 2. The subsequent C-4 → C-3
racemic methyl 2,3-dihydro-2-phenylbenzo[b]furan- migration of the aryl group followed by a concomitant
3
-carboxylate [(±)-4a or (±)-4b] in good yield cleavage of the weak C–Pb bond resulted in the cis-2,3-
(75%), but the relative configuration at the 2,3- dihydrobenzo[b]furan derivative 4b. According to the
dihydrobenzo[b]furan ring was not reported. It is fur- observation of Kapoor et al., this type of intermediate
ther noteworthy that flavone (5) could be also isolated [3b; X = Tl(ONO ) ] also explains the formation of the
2
2
as a by-product in low yield (15%) (Scheme 1).
flavone by-product 5 in the above transformation [(±)-
One year later, the transformation of (±)-1 to (±)- 1 → (±)-4a + 5] by the loss of 2-H followed by the re-
4
b with LTA in TMOF in the presence of a catalytic ductive cleavage of the weak carbon-thallium bond.
©
2012 Verlag der Zeitschrift f u¨ r Naturforschung, T u¨ bingen · http://znaturforsch.com
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I. N e´ meth et al. · Oxidative Rearrangement of Flavanones
1
O
H
H
Ph
O
Ph
i
2
3
4
ii
O
OMe
1
2
H
O
Ph
3
X
X
a
b
c
Pb(OAc)3
Tl(ONO2)2
I(Ph)(OAc)
MeO OMe
a c
3
iii
iii
iii
iii
H
H
O
Ph
CO R
O
Ph
O
Ph
O
Ph
2
OR
H
a c
H
O
O
O
4
5
6a, b
7
4
a
b
c
R
3H
R
Me
H
Me
Me
H
a
b
+
Scheme 1. (i) TMOF, 70% HClO or conc. H SO ; (ii) TTN·3H O or LTA or PIDA, (iii) H O, H , r. t.
4
2
4
2
2
In 1995, Prakash and Tanwar reported [3] that the corresponding flavone (5, C-2 phenyl is replaced by p-
ring-contraction of (±)-1 with PIDA in TMOF in the methoxyphenyl).
presence of a catalytic amount of sulfuric acid at
Recently, on the basis of NMR, ECD and chi-
room temperature also resulted in methyl 2,3-dihydro- ral HPLC studies, we have proved that the ring-
-phenylbenzo[b]benzofuran-3-carboxylate [(±)-4a or contraction of (−)-(2S)-flavanone [(−)-1] under the
±)-4b] together with cis-3-methoxyflavanone [(±)- conditions used by Prakash and Tanwar [3] takes place
a] and flavone (5) in 50%, 35% and 15% yields, stereoselectively, controlled by the configuration of the
2
(
6
respectively. Interestingly the relative stereochemistry C-2 phenyl group to result in (+)-(2S,3S)-4a, which
of the major product [(±)-4a or (±)-4b] was not de- can be isolated in moderate (25%) yield [4]. Moreover,
termined, although it was suggested that during the we have found that the synthesis of (+)-(2R,3R)-9a
0
formation of the hypervalent iodine intermediate 3c could be performed by ring-contraction of (+)-(2R)-2 -
[X = I(Ph)(OAc)], the electrophilic addition of PIDA benzyloxyflavanone (8a) under the above mentioned
at C-3 of the enol ether of (±)-1 took place anti to conditions in 48% yield, which allows the construc-
the C-2 phenyl group. Moreover, they recognized that tion of the pterocarpan skeleton with cis B/C-ring junc-
in the case of flavanones containing a p-methoxy sub- tion [(+)-(6aS,11aS)-10a] in five steps as shown in
stituent at the 2-phenyl ring, the formation of the cor- Scheme 2 [5].
responding isoflavone (7, C-3 phenyl is replaced by p-
Although this approach offered a facile enantiose-
methoxyphenyl) was also observed together with the lective route to naturally occurring biologically active
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I. N e´ meth et al. · Oxidative Rearrangement of Flavanones
1291
1
O
8
H
R1
7
2
R1
H
R2
H
3
OBn
R2
6
4
5
a
b
c
O
a c
-OCH2O-
MeO
8
H
i
ii
ii
ii
H
R1
R2
O
R1
R2
R1
R2
O
O
OBn
+
+
OBn
OBn
CO Me
H
2
O
O
9
a (48 %), 9b (-), 9c (24 %)
11b (34 %), 11c (7 %)
12c (12 %)
iii vii
R1
10
11
O
9
H
1
4
R2 8
2
3
7
H 6
O
5
10a
+
Scheme 2. (i) TTN·3H O, TMOF, HClO , r. t.; (ii) H O, H , r. t.; (iii) LiAlH , Et O, r. t.; (iv) TsCl, py., r. t.; (v) H /Pd,
2
4
2
4
2
2
MeOH; (vi) NaOMe, MeOH; (vii) PTS, C H , ∆.
6
6
pterocarpans possessing a hydroxy or alkoxy function Results and Discussion
at C-3, C-8 and C-9 [6, 7], surprisingly the treatment of
0
2
-benzyloxyflavanone (±)-8b possessing an electron-
The HPLC monitoring of the transformation of
donating methylenedioxy group at C-6 and C-7 with racemic flavanone [(±)-1] with 1.1 mol equivalents
TTN·3H O or PIDA did not give the ring-contraction of TTN·3H O in TMOF in the presence of a cat-
2
2
product [(±)-9b] at all. Instead, (±)-8b underwent 2- alytic amount of 70% perchloric acid at room
aryl migration to give the isoflavone derivative 11b in temperature has clearly indicated that the conver-
moderate yield (34%). The treatment of [(±)-8c], pos- sion of (±)-1 reached 98% in 30 minutes to re-
sessing an electron-donating methoxy group only at C- sult in a complex mixture of products as shown in
6
, with TTN·3H O led to ring-contraction [(±)-8c → Fig. 1.
2
(
±)-9c] in moderate yield (24%) accompanied by 2-
aryl migration and dehyrogenation as well [(±)-8c → nearly base line-separated, and besides rac-
±)-11c (7%) + 12c (16%)]. In the reaction of (±)- flavanone [(±)-1 (2%)], rac-methyl 2,3-dihydro-2-
c with PIDA as electrophilic reagent, only a dehydro- phenylbenzo[b]furan-3-carboxylate [(±)-4a (76%)],
genation resulting in the flavone derivative 12c (51%) flavone [5 (3%)], and isoflavone [7 (9%)] could
could be observed [8]. be identified unequivocally by comparing with au-
Many components of this mixture could be
(
8
In order to reveal the principles governing the thentic samples (see entry 1 in Table 1). Moreover,
outcome of the ring-contraction of flavanones me- the compound with t = 8.95 min could also be
R
diated by TTN·3H O, LTA and hypervalent iodine, isolated by preparative TLC and identified as methyl
2
HPLC monitoring was carried out on the reaction 2-phenylbenzo[b]furan-3-carboxylate (17) by its MS
of (±)-1 with TTN·3H O, LTA, PIDA, and [hy- and NMR data, as well as by comparison with an
2
droxy(tosyloxy)iodo]benzene (HTIB) under different authentic sample obtained by the oxidation of (±)-
conditions.
4a with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
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I. N e´ meth et al. · Oxidative Rearrangement of Flavanones
Fig. 1. HPLC pattern of
the crude product of the
transformation
of
(±)-1
with TTN·3H O at room
2
temperature.
Table 1. Yields and retention
times of the compounds of the
transformation of (±)-1.
Entry Reag.
Proc.
1
4a
4b
5
6a
6b
7
17
22
(
7.26) (7.90) (7.20) (6.30) (8.47) (7.03) (6.70) (8.95) (8.14)
1
2
3
4
5
6
TTN
TTN
TTN
LTA
PIDA
HTIB
A
B
C
D
E
E
2
15
< 1
1
4
3
76
40
45
33
66
49
–
–
–
–
–
–
3
28
3
11
10
6
< 1
–
3
1
< 1
2
1
1
< 1
18
–
9
2
3
23
2
1
3
9
3
1
2
5
< 1
< 1
4
–
–
–
–
Yields (in %) of compounds with tR (in min) given in parentheses. Proc. A – E see Exp. Section.
H
H
H
O
Ph
X
O
Ph
OMe
ONO2
ONO2
C
MeO OMe
OMe
13
3b
H
H
H
O
Ph
O
Ph
O
Ph
C(OMe)3
i
OMe
OMe
C(OMe)3
Tl
O NO
ONO2
2
14
16
15
H
O
Ph
O
Ph
CO2Me
ii
iii
CO Me
2
H
17
4a
+
Scheme 3. (i) TTN·3H O, TMOF, HClO , r. t.; (ii) H O, H , r. t.; (iii) DDQ, 1,4-dioxane, ∆.
2
4
2
(
1
DDQ) in boiling dry dioxane [4]. The formation of
7 could be easily explained by a five-step pathway traction of 3b led to the 2,3-dihydro-2-phenylbenzo-
starting from intermediate 3b (see Scheme 1) as shown [b]furan derivative 13 possessing a dimethoxymethyl
In the first step, the stereo-controlled ring con-
in Scheme 3.
carbonium ion function at C-3. Its stabilization by
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I. N e´ meth et al. · Oxidative Rearrangement of Flavanones
1293
1
O
2 Ph
O
O
2
3
ii
i
3
7
ONO2
X
Ph
Ph
H
MeO OMe ONO2
MeO OMe
MeO OMe
3a
19
18
TTN·3H2O
O
OMe
OMe
O
OMe
O
OMe
CO Me
ii
4
3
ONO2
Tl
Ph ONO2
3
4
C
2
Ph
± ±)22
Ph
OMe
MeO OMe
(
21
20
+
Scheme 4. (i) TTN·3H O, TMOF, 70% HClO , r. t.; (ii) H O, H , r. t.
2
4
2
a simple deprotonation resulted in racemic 2-phenyl- tant cleavage of the week carbon–thallium bond fol-
0
0
3
-(2 ,2 -dimethoxy)methylenebenzo[b]furan [(±)-14], lowed by a deprotonation (3a→18→19) as shown in
which reacted with TTN·3H O under product con- Scheme 4.
2
trol [9] to afford the corresponding thallium adduct
Due to the well-known polarity of the enol ether
1
5 possessing the bulky phenyl and trimethoxymethyl function of 19, the addition of TTN took place at po-
groups in the thermodynamically preferred anti posi- sition C-3 leading to 20. In the next step, it underwent
tion. The 2-phenyl-3-trimethoxymethylbenzo[b]furan a C-4 → C-3 aryl group migration with simultaneous
(
16) formed by an oxidative elimination, and subse- reductive cleavage of the C-3 carbon–thallium bond to
quent hydrolysis during the workup gave methyl 2- result in the corresponding 2,3-dihydrobenzo[b]furan
phenylbenzo[b]furan-3-carboxylate (17). derivative 21, which on treatment with water during
◦
∗
∗
If the reaction of (±)-1 was carried out at -10 C, the workup gave (±)-(2S ,3S )-22. The decrease of the
it took place significantly more slowly as indicated yield of isoflavone (7) has been found indeed commen-
by the 85% conversion in 30 minutes, and there was surable with the yield of 22 (entry 3). The treatment of
a considerable change in the ratio of the products 7 with TTN·3H O in TMOF in the presence of a cat-
2
formed under these conditions (see entry 2 in Table 1). alytic amount of 70% perchloric acid at room tempera-
According to our expectation the formation of the enol ture for 30 min resulted in a mixture of products, from
ether 2 took place more slowly, and therefore the di- which (2S*,3S*)-22 could be isolated by preparative
rect transformation of racemic flavanone [(±)-1] by TLC.
TTN·3H O via its enol form into flavone (5) as de-
Interestingly, the longer time for the formation of
2
scribed by Varma and Varma [10] took place as well, enol ether 2 has also influenced the yield of (±)-4a (see
which significantly increased the yield of 5 (from 3 entries 1 and 3 in Table 1). According to our expecta-
to 28%). Remarkably, the overall yield of flavone (5) tion the yield of 5 did not change (3%), but the yield of
(
28%) and benzo[b]furan 17 (9%) did not significantly (±)-4a increased by 31%. This clearly indicated that
deviate from the decrease in yield of the ring con- a polymerization of enol ether 2 took also place due to
traction product (±)-4a (40%). Moreover, a substan- the presence of 70% perchloric acid.
tial decrease of the yield of isoflavone (7) could also
Both TLC and HPLC monitoring of the transfor-
be observed. The by-product related to t = 8.14 min, mation of (±)-1 by LTA under the conditions used by
R
formed in 0.8% yield, could be isolated by prepara- Khanne [2] have clearly shown that the conversion of
tive TLC. Its structure has been established by NMR (±)-1 reached 99% in 2 hours, and formation of (±)-
1
13
(
H, C, NOESY, COSY, HSQC, HMBC) and MS 4a (33%), 5 (11%), 6a, b (1%, 18%),7 (23%), and 17
evidences to be the methyl 2,3-dihydro-2-methoxy-3- (1%) could be detected (entry 4 in Table 1). In contrast
∗
∗
phenylbenzo[b]furan-3-carboxylate of (2S ,3S ) con- to the observation of Khanne, the formation of (±)-4b
figuration [(±)-22]. On the basis of its structure, it may could not be observed at all.
form from the precursor 19, which can be obtained
from 3a by a 2→3 phenyl migration with concomi- 1 by PIDA or HTIB in the presence of sulfuric acid
The HPLC monitoring of the transformation of (±)-
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I. N e´ meth et al. · Oxidative Rearrangement of Flavanones
Fig. 2. HPLC pattern of the
crude product of the transfor-
mation of (±)-1 with PIDA at
room temperature.
Fig. 3. HPLC pattern of the
crude product of the transfor-
mation of (±)-1 with HTIB at
room temperature.
in TMOF at room temperature was also carried out. In ring, two arrangements of the C-3 phenyl iodonium
both cases the transformations took place significantly acetate moiety are feasible for (±)-3c as shown in
more slowly than with TTN·3H O, and their product Scheme 5.
2
profiles were similar as shown in Figs. 2 and 3, but sig-
The computational data obtained by relaxed scans
nificantly different from those obtained by TTN·3H O performed along the C-3–I bond clearly showed that
2
(see Fig. 1). In good agreement with the observation of the cleavage of the I–OAc bond took place simulta-
Prakash and Tanwar, [3] the ring contraction of (±)-1 neously with that of the C-3–I bond [12]. Therefore
by PIDA led to (±)-4a (66%) as the main product, and in case of conformer A where the acetoxy group is
the formation of flavone (5) was also preferred (entry in proximity of 2-H, it could be simply removed by
5
in Table 1).
the leaving acetoxy group resulting in 5 with a higher
The preferred formation of flavone (5) with PIDA yield (10%) than in case of TTN·3H O (3%). The
2
as oxidizing agent could be readily explained by activation energy of this transformation calculated at
quantum-chemical calculations. If both (±)-4a and the ONIOM(B3LYP/LANL2DZ:AM1) level has been
−
1
5
form via the intermediate (±)-3c as depicted in found to be only ∼45 kJ mol which also indicates
Scheme 1, the preferred formation of 3c may have a de- that oxidative elimination of 3c to flavone (5) must
cisive role in the outcome of this reaction. Based on be a preferred pathway, which has been observed in-
the T-shaped geometry of iodine(III) compounds well deed experimentally. In the other case (conformer B),
documented in the literature [11] and the preferred the carbenium ion 23 is formed which may be strongly
half-chair conformation of the fused O-heterocyclic stabilized by a neighboring methoxy group to give the
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I. N e´ meth et al. · Oxidative Rearrangement of Flavanones
1295
+
Scheme 5. (i) PIDA, TMOF, HClO , r. t.; (ii) H O, H , r. t.
4
2
oxenium ion 24, and its transformation results in the matography software; UV detector: UV-2075 Plus, Pump
−
1
mixture of (±)-4a and 7 in 66 and 2% yield, respec- PU-2089 Plus. The flow rate was 1 mL min . An injec-
◦
tion volume of 20 µL and a column temperature of 25 C
tively.
2
was used. The C18 5 µm, 150 × 4.6 mm Gemini chromato-
graphic column (Phenomenex) was used for these studies.
Conclusion
A solution of KI (in CH CN) was used for dead time (t ) de-
3
D
termination. Retention times (t ) were measured in minutes.
Flavanone [(±)-1], when treated with TTN·3H O
R
2
A mixture of CH CN (HPLC grade) and H O (HPLC grade)
3
2
in TOMF in the presence of 70% perchloric acid at
room temperature, rearranges to methyl 2,3-dihydro-2-
phenylbenzo[b]furan-3-carboxylate [(±)-4a] in 76%
yield, and beside this compound not only flavones
was used as a mobile phase. The gradient program was lin-
ear from 50% to 100% in 8 min and then held for 4 min.
A detection wavelength of 254 nm was chosen, and the mea-
sured peak of the compounds was corrected on the basis of
the ppm value obtained from the HPLC chromatogram of the
corresponding analytically pure compound.
(
5), as published by Kapoor et al. [1], but also
cis-3-methoxyflavanone (6a), cis-3-hydroxyflavanone
6b), isoflavone (7), methyl 2-phenylbenzo[b]furan-3-
(
Analytical and preparative TLC were done on
plates Kieselgel 60 F254 (Merck). The reagents thal-
lium(III) nitrate [Tl(NO ) ·3H O)], lead tetraacetate
∗
∗
carboxylate (17), and 2S 3S -2-methoxy-3-methoxy-
carbonyl-3-phenyl-2,3-dihydrobenzo[b]furan [(±)-22]
3
3
2
are formed in < 1, 1, 9, 3 and < 1% yield, respec- (Pb(OAc) , phenyliodonium diacetate [PhI(OAc) ] and [hy-
4
4
tively. In contrast to the observation of Khanna [2], the droxyl(tosyloxy)iodo]benzene [PhI(OH)OTs], as well as the
treatment of (±)-1 with LTA in TMOF in the presence compounds rac-flavanone (1), flavone (5) and isoflavone (7)
of a catalytic amount sulfuric acid did not afford (±)- were purchased from Sigma-Aldrich. Compounds (±)-4a,
4
b, 17, [4], (±)-6a, [13] and (±)-6b [14] were prepared
4
6
b in 80% yield as a sole product, but (±)-4a, 5, 6a,
b, 7, and 17 were formed in 33, 11, 1, 18, 23 and 1%
according to the literature. For workup the solutions were
dried (MgSO ) and concentrated in vacuo. H and C NMR
spectra were recorded with a Bruker AM-360 instrument in
CDCl with TMS as internal standard. The chemical shifts
1
13
4
yield, respectively. The treatment of (±)-1 with PIDA
reported by Prakash and Tanwar [3] led in our hands to
3
(
±)-4a (66%), 5 (10%), and (±)-6a (< 1%) in signifi-
are given on the δ scale in ppm.
cantly different yields from those reported (50%, 15%,
3
5%, resp.). Moreover the formation of 7 (2%) and 17 Procedures for the transformations of racemic flavanone
(
2%) could also be detected. In case of HTIB a similar [(±)-1]
profile of products has been observed.
Procedure A: After 5 min. Tl(NO ) ·3H O (1.1 mmol)
3
3
2
was added to a stirred solution of (±)-1 (1 mmol) in TMOF
Experimental Section
(
2 mL) and 70% aqueous HClO (xx mL, 3 mmol) at r. t.,
4
Analytical RP-HPLC was performed on a Jasco HPLC and the reaction mixture was stirred at r. t. for 30 min. The
System; data acquisition was performed using Borvin chro- reaction mixture was diluted with CH Cl and the Tl(I) salt
2
2
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I. N e´ meth et al. · Oxidative Rearrangement of Flavanones
∗
∗
filtered off. The organic phase was washed with a saturated 2S ,3S -Methyl 2,3-dihydro-2-methoxy-3-phenylbenzo-
solution of sodium hydrogen carbonate and water and dried. [b]furan-3-carboxylate (22)
The evaporation of the solution gave a crude product as an
After 5 min 490 mg (1.1 mmol) of TTN·3H O was added
2
oil. The compounds detected by HPLC are given in entry 1
of Table 1.
to a stirred solution of 222 mg (1 mmol) isoflavone (7) in
trimethyl orthoformate (2 mL) and 70% HClO (0.19 mL) at
4
Procedure B: After 5 min Tl(NO ) ·3H O (1.1 mmol)
3
3
2
r. t., and the stirring was continued for 30 min with monitor-
ing of the reaction by TLC (hexane-ethyl acetate, 4 : 1, v/v).
The reaction mixture was diluted with CH2Cl2 and stirred
further for 15 min. The thallium salt was removed by filtra-
tion and the organic extract washed with a saturated solu-
tion of sodium hydrogen carbonate and water. It was dried
and the solvent removed under reduced pressure. The com-
was added to a stirred solution of (±)-1 (1 mmol) in TMOF
◦
(
2 mL) and 70% HClO (3 mmol) at –10 C, and the reaction
4
◦
mixture was stirred at –10 C for 30 min. Workup was the
same as in Procedure A. The compounds detected by HPLC
are given in entry 2 of Table 1.
Procedure C: After 30 min Tl(NO ) ·3H O (1.1 mmol)
3
3
2
was added to a stirred solution of (±)-1 (1 mmol) in TMOF
pound of R = 0.79 was isolated by column chromatography
f
(
2 mL) and 70% HClO (3 mmol) at r. t., and the reaction
4
on silica gel, using hexane-ethyl acetate (6 : 1, v/v) as eluent,
and its purification by preparative TLC (hexane-ethyl acetate
mixture was stirred at r. t. for 30 min. Workup was the same
as in Procedure A. The compounds detected by HPLC are
given in entry 3 of Table 1.
(
(
4 : 1, v/v)) resulted in 22 as a colorless oil. Yield 58.9 mg
1
21%). – H NMR (360 MHz, CDCl ): δ = 3.15 (3H, s,
3
Procedure D: After 5 min Pb(OAc)4 (1.1 mmol) was
added to a stirred solution of (±)-1 (1 mmol) in TMOF
OCH ), 3.28 (3H, s, COOCH ), 5.12 (1H, s, 2-H), 7.06 (d,
3
3
1
H, 4-H, J4,5 = 8.2 Hz), 7.13 (t, 1H, 5-H), 7.43 – 7.53 (over-
(2 mL) and conc. sulfuric acid at r. t., and the reaction mix-
0
0
0
0
0
lapping signals, 5H, 2 , 3 , 4 , 5 , 6 -H), 7.58 (dd, 1H, 6-H),
ture was stirred at r. t. for 2 h. Workup was the same as in
Procedure A. The compounds detected by HPLC are given
in entry 4 of Table 1.
1
3
8
(
(
1
.04 (dd, 1H, 7-H, J6,7 = 7.8 Hz, J5,7 = 1.7 Hz ). – C NMR
90 MHz, CDCl ): δ = 52.9 (COOCH ), 56.8 (OCH ), 81.06
3
3
3
C-3), 105.9 (C-2), 118.0 (C-4), 120.4 (C-9), 122.0 (C-5),
Procedure E: After 5 min PhI(OAc)2 or PhI(OH)OTs
0 0 0 0
27.5 (C-4 ), 127.6 (C-7), 128.2 (C-3 , C-5 ), 129.0 (C-2 ,
(
(
1.08/1.08 mmol) was added to a stirred solution of (±)-1
0
0
C-6 ), 133.3 (C-1 ), 136.1 (C-6), 156.4 (C-8), 188.3 (CO) –
1 mmol) in TMOF (2 mL) and conc. sulfuric acid (xx mL)
+
HRMS: m/z = 285.102 [M+H] .
at r. t., and the reaction mixture was stirred at r. t. for 2 h. The
reaction mixture was poured into water, and products were
Acknowledgement
extracted with CH Cl , washed with water and dried. After
2
2
evaporation of the solution the crude product was obtained as
We are grateful to the National Research Foundations
an oil. The compounds detected by HPLC are given in entry (OTKA K81701 and TAMOP 4.2.2./B-10/1) for the financial
5
and 6 of Table 1, respectively.
support of our research.
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1] M. S. Khanna, O. V. Singh, C. H. P. Garg, R. P. Kapoor,
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[
1
Unauthenticated
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