N1,N10-Ethylene-bridged flavinium salts derived from l-valinol: synthesis and catalytic activity in H2O2 oxidations

Article abstract of DOI:10.1016/j.tetlet.2009.12.096

Three chiral N¹,N¹⁰-ethylene-bridged flavinium salts with a stereogenic centre derived from l-valinol are prepared and investigated as oxidation catalysts. These salts efficiently catalyse chemoselective H₂O₂ oxidation of sulfides to sulfoxides and the oxidation of 3-phenylcyclobutanone to the corresponding lactone at room temperature. The flavinium salts react with hydrogen peroxide to form flavin-10a-hydroperoxide, which is the agent responsible for oxidation of the substrate.

Full text of DOI:10.1016/j.tetlet.2009.12.096

Tetrahedron Letters 51 (2010) 1083–1086
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Tetrahedron Letters
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N1,N10-Ethylene-bridged flavinium salts derived from L-valinol: synthesis
and catalytic activity in H2O2 oxidations
a
a,
b
a
*
ˇ
ˇ
ˇ
ˇ
Jirí Zurek , Radek Cibulka , Hana Dvoráková , Jirí Svoboda
a Department of Organic Chemistry, Institute of Chemical Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic
b Central Laboratories, Institute of Chemical Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Three chiral N1,N10-ethylene-bridged flavinium salts with a stereogenic centre derived from
L-valinol are
Article history:
Received 16 October 2009
Revised 8 December 2009
Accepted 16 December 2009
Available online 24 December 2009
prepared and investigated as oxidation catalysts. These salts efficiently catalyse chemoselective H2O2 oxi-
dation of sulfides to sulfoxides and the oxidation of 3-phenylcyclobutanone to the corresponding lactone
at room temperature. The flavinium salts react with hydrogen peroxide to form flavin-10a-hydroperox-
ide, which is the agent responsible for oxidation of the substrate.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Organocatalysis
Oxidation
Flavinium salts
Hydrogen peroxide
Oxidation with hydrogen peroxide or oxygen catalysed by flavi-
nium salts 1 or 2 seems to be a promising organocatalytic method
that fulfils all the criteria for environmentally benign processes.1–3
Flavinium salts are usually considered as flavoenzyme mimics that
can transform, for example, sulfides into sulfoxides,4–12 tertiary
amines into N-oxides,4,13 cyclic ketones into lactones14 and hydra-
zine into diimide.15,16 In several instances, chiral flavinium salts
affording sulfoxides17,18 or esters19 with moderate enantioselectiv-
ity have also been described. The mechanism of flavinium salt
catalysis in oxidations involves in situ formation of flavin hydro-
peroxide, which is the agent that oxidises the substrate.1–3
Although oxidations catalysed by flavinium salts have been stud-
ied in detail, the flavinium catalysts already investigated are limited
to 5-alkylisoalloxazinium salts 1 (derivatives of natural flavins)4,9–
12,14–20 and 5-alkylalloxazinium salts 2 (non-natural derivatives that
are also considered as flavinium salts in the literature).5–9,12,13 Both
5-alkylflavinium salts 1 and 2 form flavin-4a-hydroperoxides 1-
OOH and 2-OOH by reaction with hydrogen peroxide or by the reac-
tionsequenceincludingreductiontodihydroderivative1-H2 or2-H2
(with hydrazine or sodium dithionate) followed by reaction with
molecular oxygen (Scheme 1).1–3 The dihydro derivatives 1-H2 and
2-H2 have also been isolated and used as efficient catalysts in
H2O2 oxidations.5–8,13 In such cases, the dihydro derivatives are in
fact precursors of the corresponding salts 1 and 2 which are formed
in situ from 1-H2 and 2-H2 by the action of oxygen. Surprisingly,
there have been no reports on reactions of N1,N10-ethylene-bridged
flavinium salts 3 with a quaternary nitrogen at position 10. The only
exception was a study of amine oxidation to aldehydes in the pres-
ence of substituted 1,10-ethyleneisoalloxazinium chlorides 3a–c
(Scheme 2).21
R1
N
R1
N
R4
R3
N
O
O
R4
R3
N
O
N
N
N
R2
N
R2
X-
X-
Et
Et
O
1
2
R1
N
R1
N
R4
R3
N
O
O
R4
R3
N
O
N
N
N
Et
R2
N
R2
O
O
Et
O
O
O
H
H
1-OOH
2-OOH
R1
N
H
N
R1
H
R4
R3
N
O
R4
R3
N
O
N
N
N
Et
R2
N
Et
R2
O
O
1-H2
2-H2
* Corresponding author. Tel.: +420 220444279; fax: +420 220444288.
E-mail address: cibulkar@vscht.cz (R. Cibulka).
Scheme 1. Structures of 5-alkylflavinium salts 1 and 2, and the corresponding
flavin-4a-hydroperoxides, and dihydro derivatives.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.12.096

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J. Zurek et al. / Tetrahedron Letters 51 (2010) 1083–1086
1084
CH3
H3C
R2
R1
N
N
O
O
N
N
O
O
R
NH
N
Cl-
N
N
-
Cl
3
4
3a: R1 = R2 = H
4a:
R = H
1
2
3b:
R = H, R = Cl
3c: R1 = CF3, R2 = H
4b:
4c:
R = CH3
R = Bn
Scheme 2. N1,N10-Ethylene-bridged flavinium salts.
Salts 3 are known to form 10a-adducts with primary and sec-
ondary amines, hydrazine or methanol.22 Therefore, we expected
that compounds 3 could also add hydrogen peroxide and thus
could be used as catalysts for oxidations in a similar manner as
flavinium derivatives 1 and 2. In the present study, we modified
the structure of ethylene-bridged salts 3 by incorporation of a ste-
reogenic centre into the ethylene bridge. We assumed that the pro-
posed chiral flavinium salts 4 (Scheme 2) could be easily prepared
using natural amino acids as the source of chirality. The aim of this
study was to verify the synthetic availability of chiral ethylene-
Figure 1. Oxidation of thioanisole with H2O2 catalysed by flavinium salts 4a–c
compared to the non-catalysed control reaction (blank). Conditions: n(thioani-
sole) = 0.255 mmol, n(H2O2) = 0.392 mmol, n(4) = 5.1 lmol, T = 25 °C, solvent =
CD3OD/H2O.
iPr
iPr
N
N
N
O
O
H
N
N
N
O
OH
N
N
bridged flavins 4 starting from an amino acid derivative (L-valinol
was used in this study) and to investigate the ability of the pre-
pared salts to catalyse oxidations with hydrogen peroxide.
Scheme 4. Possible oxo-enol tautomerism in the case of salt 4a.
The synthesis of flavinium compounds 4 was performed analo-
gously to the procedure described for derivatives 3 starting from
1-fluoro-2-nitrobenzene (Scheme 3).21 Catalytic hydrogenation of
5 gave N-substituted diamine 6, which was condensed with allox-
ane hydrate (7a) to form flavin 8a. The 3-methyl 8b and 3-benzyl
8c derivatives were obtained by alkylation of flavin 8a with methyl
iodide and benzyl bromide, respectively. Alternatively, 8b was pre-
pared by condensation of 6 with N-methylalloxane hydrate (7b)23
(for details on the synthesis of 8 see the Supplementary data). The
synthesis of salts 4 was completed by heating 10-(2-hydroxy-
ethyl)flavins 8 in thionyl chloride under an argon atmosphere.24
Flavins 8a and 8b have already been reported but the authors
did not provide any details on their synthesis.25 They predicted
possible steric crowding between the isoalloxazine plane and the
substituents on the stereogenic carbon attached to N10 in 8. Indeed,
we observed two sets of signals in a ratio of approximately 2:1 in
the 1H NMR spectra of 8a–c corresponding to the presence of two
diastereomers of 8 differing in configuration at the N10–C bond (for
characterisation of 8, see the Supplementary data).
The newly prepared compounds
4 were investigated as
catalysts in various H2O2 oxidations known to be catalysed by
flavinium salts: sulfoxidation, oxidation of tertiary amines and
Baeyer–Villiger (BV) oxidation.1,2 To be able to rank the efficiency
of salts 4 compared to the reactivity of the previously reported
flavinium catalysts, we typically applied reaction conditions analo-
gous to those used in previous studies.5,14
The catalytic activity of salts 4 in the oxidation of sulfides with
hydrogen peroxide was investigated under the conditions used by
Minidis and Bäckvall with deuterated methanol as the solvent, a
small excess of hydrogen peroxide, 2 mol % of the catalyst (relative
to the substrate) at room temperature (for details see the Supple-
mentary data).5 Reactions were performed in NMR tubes and the
conversion was monitored by 1H NMR spectroscopy. Thioanisole
was used first as a model substrate. Time course results for thioani-
sole oxidation in the presence of 4a, 4b, and 4c (Fig. 1) clearly show
that all the tested salts accelerated thioanisole oxidation compared
to the control non-catalysed reaction. In contrast to the substantial
H
O
N
O
R
iPr
HO
N
HO
iPr
iPr
iPr
O
H2N OH
K2CO3
OH
N
OH
OH
7a: R = H
N
N
O
R
NH
F
NH
H2, Pd/C
methanol
7b: R = CH3
N
n-butanol
acetic acid
NO2
NO2
5
NH2
6
O
8a
CH3I
BnBr
or
(84%)
(99%)
K2CO3
acetone
iPr
iPr
OH
N
8b, 8c
N
N
O
O
N
O
SOCl2
dichloromethane
8a:
8b:
8c:
R = H (45%)
R = CH3 (85%)
R = Bn (78%)
N
N
Cl-
N
R
N
4
R
O
8
(88-95%)
Scheme 3. Synthesis of flavinium salts 4.

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J. Zurek et al. / Tetrahedron Letters 51 (2010) 1083–1086
1085
rate enhancement observed for the 3-alkylated salts 4b and 4c, the
catalytic efficiency of non-substituted salt 4a was relatively low,
probably because of oxo–enol tautomerism (Scheme 4).21,22 This
equilibrium is in competition with the formation of the oxidising
species, flavin hydroperoxide, which is the product of hydrogen
peroxide addition to the flavinium salt.
To gain an insight into the reactivity of 4b in H2O2 sulfoxida-
tions, it was used for the oxidation of several other substrates
(Table 1). As expected, oxidation of an electron-rich aliphatic sul-
fide (entry 5) was faster than that of aromatic sulfides (entries
1–4). In all cases, no over-oxidation was observed and sulfoxides
were detected as the only products; no side oxidation of the double
bond in allyl phenyl sulfide occurred (entry 4). Thus, from the point
of view of selectivity, the oxidising system with 4b is comparable
to that with 5-alkyl derivative 2a-H2 (2a-H2 was used as a precur-
sor of 2a; for the structure see Scheme 1, R1 = R2 = CH3,
R3 = R4 = H).5,6 Nevertheless the efficiency of 4b is slightly lower
than that of 2a-H2 (Table 1). Although we observed rate enhance-
ment from 11:1 to 19:1 in the presence of 4b, the addition of 2a-H2
accelerated sulfoxidation by a factor ranging from 12.5 to 74 com-
pared to the non-catalysed reaction.
Figure 2. Oxidation of triethylamine with H2O2 catalysed by flavinium salt 4b.
Course of non-catalysed reaction (blank) is shown for comparison. Conditions:
n(triethylamine) = 0.255 mmol, n(H2O2) = 0.392 mmol, n(4b) = 5.1 lmol, T = 25 °C,
solvent = CD3OD/H2O.
iPr
According to the initial reaction rate, salt 4b efficiently cata-
lysed the oxidation of tertiary amines to N-oxides under identical
conditions to those for sulfoxidation (for details see the Supple-
mentary data). The rate enhancement for amine oxidation by 4b,
determined from the initial rate, is even comparable to that for
2a (Table 1, entries 6 and 7).13 However, oxidation catalysed by
4b rapidly decelerates and at conversion rates of >15% the reaction
course corresponds to the non-catalysed process (Fig. 2). This is
probably caused by decomposition of the 1,10-ethylene-bridged
flavinium catalyst under basic conditions. We confirmed the struc-
ture of the decomposition product, ester 9 (Scheme 5), in an inde-
N
N
N
O
OCH3
9
Scheme 5. The structure of the decomposition product of 4b.
pendent experiment in which 9 was formed quantitatively by
heating 4b in methanol in the presence of triethylamine (see the
Supplementary data for experimental details). An analogous
product was previously observed on reaction of
3 with
benzylamine.21,22
Table 1
Oxidation of sulfides and amines with H2O2 in the presence of 2 mol % 4ba
No alloxazinium salts have been investigated as catalysts for BV
oxidation to date. Therefore, to test the catalytic activity of 4 in this
reaction, we used the conditions described for BV oxidation in the
presence of isoalloxazinium salts 1 (R1 = Ph, R2 = CH3, R3 = R4 = H),
with t-BuOH as the solvent, 5 mol % of the catalyst and two equiv-
alents of H2O2 at room temperature.14 In the presence of 4b, oxida-
tion of 3-phenylcyclobutanone (Scheme 6) was complete after 6 h.
By contrast, only the starting material was isolated for the non-cat-
alysed oxidation (for details see the Supplementary data).
R2
R2
R1
R1
H2O2
S
S
cat. 4b
O
CD3OD/H2O
R3N
R3NO
Entry Substrate
Conversion after 1 h (%)
Rate
enhancementb
5,13
4b
2a-H2
A question arises regarding the structure of the flavin hydroper-
oxide responsible for H2O2 oxidations catalysed by salts 4. To the
best of our knowledge, all the described adducts of ethylene-
bridged flavinium salts 3 have a nucleophile (amine, water or
methanol) connected to position 10a.22 Thus, it is reasonable to
assume that hydrogen peroxide forms the corresponding flavin-
10a-hydroperoxides with 3 and 4. It is not possible to analyse
hydroperoxides under oxidation conditions because solvent–flavi-
nium salt adducts predominate in solution in protic solvents.22
Therefore, we generated flavin hydroperoxide in an independent
experiment by adding four equivalents of H2O2 (in the form of a
urea–H2O2 complex) to an acetonitrile solution of 4b in the
presence of potassium carbonate as a base26 (the formation of
4b-OOH in this solution was confirmed initially by mass spectrom-
etry). As expected, two sets of signals in the 1H and 13C NMR spec-
1
56
53
19:1
—
CH3
S
H3C
2
16:1 74:1c
17:1 36:1d
CH3
S
H3CO
3
66
CH3
S
4
37
93
11:1
—
S
13:1 12.5d
26:1 27:1e
43:1 67:1e
2S
5
6
7
Et3N
Ph–CH2N(CH3)2
18
14
a
Conditions: n(substrate) = 0.255 mmol, n(H2O2) = 0.392 mmol, n(4) = 5.1
T = 25 °C.
lmol,
b
Rate enhancement for catalysed versus non-catalysed reactions calculated by
dividing the rate of the catalysed reaction by that of the non-catalysed reaction at
low conversion5 (up to 10%).
H2O2
Ph
4b
cat.
O
Ph
O
c
O
t-BuOH/H2O
1.83 mol % catalyst.
1.6 mol % catalyst.
2.5 mol % catalyst.
d
e
Scheme 6. BV oxidation of 3-phenylcyclobutanone catalysed by 4b.

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J. Zurek et al. / Tetrahedron Letters 51 (2010) 1083–1086
9. Imada, Y.; Iida, H.; Ono, S.; Masui, Y.; Murahashi, S.-I. Chem. Asian J. 2006, 136.
10. Imada, Y.; Ohno, T.; Naota, T. Tetrahedron Lett. 2007, 48, 937.
11. Baxová, L.; Cibulka, R.; Hampl, F. J. Mol. Catal. A 2007, 277, 53.
OOH
N
OOH
N
iPr
iPr
ˇ
12. Cibulka, R.; Baxová, L.; Dvoráková, H.; Hampl, F.; Ménová, P.; Mojr, V.; Plancq,
N
N
O
N
N
O
B.; Sayin, S. Collect. Czech. Chem. Commun. 2009, 74, 973.
13. Bergstad, K.; Bäckvall, J.-E. J. Org. Chem. 1998, 63, 6650.
N
N
CH3
CH3
14. Mazzini, C.; Lebreton, J.; Furstoss, R. J. Org. Chem. 1996, 61, 618.
15. Imada, Y.; Iida, H.; Naota, T. J. Am. Chem. Soc. 2005, 127, 14544.
16. Smit, C.; Fraaije, M. W.; Minnaard, A. J. J. Org. Chem. 2008, 73, 9482.
17. Shinkai, S.; Yamaguchi, T.; Kawase, A.; Kitamura, A.; Manabe, O. Chem.
Commun. 1987, 1506.
O
O
4b-OOH
Scheme 7. Structure of flavin-10a-hydroperoxide 4b-OOH (both diastereomers).
18. Shinkai, S.; Yamaguchi, T.; Manabe, O.; Toda, F. Chem. Commun. 1988, 1399.
19. Murahashi, S.-I. Angew. Chem., Int. Ed. Engl. 1995, 34, 2443.
20. Murahashi, S.-I.; Ono, S.; Imada, Y. Angew. Chem., Int. Ed. 2002, 41, 2366.
21. Li, W.-S.; Zhang, N.; Sayre, L. M. Tetrahedron 2001, 57, 4507.
22. Li, W.-S.; Sayre, L. M. Tetrahedron 2001, 57, 4523.
tra corresponding to the two diastereomers of 4b-OOH (Scheme 7)
were observed. The 3:1 ratio of signals in the 1H NMR spectrum
indicates a good diastereoselectivity for H2O2 addition to 4b, which
is the result of steric hindrance from the isopropyl group. From the
13C NMR spectra it was evident that the signal for the C-10a atom
was shifted from d 142.9 in salt 4b to d 85.5 (major isomer) and d
86.9 (minor isomer) in the adduct. Assignment of the C-10a signal
for the salt and adducts was made on the basis of the HMBC spec-
trum, which contained signals corresponding to coupling between
the hydrogen atoms of the CH2 and CH groups in the bridge and the
C-10a carbon atom.
The stereodifferentiation observed in the formation of 4b-OOH
prompted us to test salt 4b as a catalyst in stereoselective oxida-
tions. Unfortunately, preliminary experiments on the sulfoxidation
of thioanisole in methanol at ꢀ20 °C showed only low stereoselec-
tivity (<5% ee; for experimental details see the Supplementary
data).
23. N-Methylalloxane monohydrate is not commercially available. It was prepared
according to the procedure described in Ref. 12.
24. General procedure for synthesis of 4: thionyl chloride (1 mL) was added to a
slurry of flavin 8 (0.3 mmol) in dry CH2Cl2 (5 mL) and the reaction mixture was
stirred under an argon atmosphere for 24 h. Hexane (5 mL) was added and the
precipitate was collected by filtration, washed with hexane and dried under
reduced pressure. (S)-1-Isopropyl-1,2-dihydro-4,6(3H,5H)-dioxo-benzo[g]imi-
dazo[1,2,3-i,j]pteridin-12-ium chloride (4a): yield 95%. Yellow crystals,
mp = 233–237 °C. ½a D25
ꢁ
ꢀ196.2 (c 0.183, MeOH). 1H NMR (300 MHz, DMSO-
d6): d 0.74 (d, 3 H, J = 6.6 Hz, CH3), 1.14 (d, 3H, J = 6.9 Hz, CH3), 2.75–2.93 (m,
1H, CH(CH3)2), 4.53 (dd, 1H, J = 10.8, 10.3 Hz, CHA2 ), 4.72 (dd, 1H, J = 10.7,
4.5 Hz, CHB2), 5.96–6.14 (m, 1H, CH-CH2), 8.10 (dd, 1H, J = 7.5, 7.5 Hz, arom. H),
8.32 (dd, 1H, J = 8.4, 7.5 Hz, arom. H), 8.49 (d, 1H, J = 8.1 Hz, arom. H), 8.58 (d,
1H, J = 8.1 Hz, arom. H), 12.83 (s, 1 H, NH). 13C NMR (75 MHz, DMSO-d6): d
14.5, 18.7, 29.9, 45.9, 69.6, 118.5, 128.5, 131.7, 133.5, 136.1, 138.7, 140.1,
144.7, 147.1, 158.7. Anal. Calcd for C15H15ClN4O2ꢂ2H2O (354.80): C, 50.78; H,
5.40; N, 15.79. Found: C, 50.51; H, 5.06; N, 15.86.
(S)-1-Isopropyl-1,2-dihydro-5-methyl-4,6(3H,5H)-dioxo-benzo[g]imidazo[1,2,3-
i,j]pteridin-12-ium chloride (4b): yield 90%. Yellow crystals, mp 157.6–
164.3 °C. ½a 2D5
ꢁ
ꢀ195.0 (c .502, MeOH). 1H NMR (600 MHz, CD3CN): d 0.75 (d,
In conclusion, the N1,N10-ethylene-bridged alloxazinium salts 4
catalyse sulfide oxidations and BV oxidations with hydrogen per-
oxide. Salts 4 form 10a-hydroperoxide 4-OOH in situ, which can
oxidise various substrates in an analogous manner to its 4a-deriv-
atives1,2 1-OOH and 2-OOH. The catalytic efficiency of 4b is compa-
rable to that of alloxazinium salts already reported. The relatively
easy synthesis and the possibility of introducing a stereogenic cen-
tre into the side-chain make these ethylene-bridged alloxazinium
salts promising catalysts. We found that only the isopropyl group
does not result in enantioselectivity during sulfoxidation. On the
other hand, the structures of catalysts 4 can be modified which
could lead to efficient enantioselective catalysts. To the best of
our knowledge, this study is the first example of the application
of a flavinium salt with a quaternary nitrogen at position 10 for
the catalysis of H2O2 oxidations.
3H, J = 6.86 Hz, CH3), 1.19 (d, 3H, J = 6.8 Hz, CH3), 2.92 (m, 1H, CH(CH3)2), 3.43
(s, 3H, N–CH3), 4.65 (dd, 1H, J = 11.4, 4.9 Hz, CHA2 ), 4.69 (dd, 1 H, J = 11.4,
10.2 Hz, CHB), 6.04 (m, 1H, CH–CH2), 8.09 (dd, 1H, J = 6.7, 1.6 Hz, arom. H),
8.30–8.37 (2m, 2H, arom. H), 8.54 (d, 1H, J = 8.5 Hz, arom. H). 13C NMR
(150.9 MHz, CD3CN): d 14.1 (CH3), 18.2 (CH3), 29.3 (N–CH3), 30.4 (CH(CH3)2),
46.9 (CH2), 70.5 (CH–CH2), 118.4, 132.1, 134.3 and 140.0 (arom. CH), 129.7,
133.6, 142.0 and 142.9 (arom. quat. C), 147.4 and 158.2 (CO). Anal. Calcd for
C16H17ClN4O2ꢂ2H2O (368.83): C, 52.11; H, 5.74; N, 15.19. Found: C, 51.77; H,
5.97; N, 15.20.
(S)-1-Isopropyl-1,2-dihydro-5-benzyl-4,6(3H,5H)-dioxo-benzo[g]imidazo[1,2,3-
i,j]pteridin-12-ium chloride (4c): yield 88%. Yellow crystals, mp 133.7–
141.1 °C. ½a 2D5
ꢁ
ꢀ177.4 (c 0.438, MeOH). 1H NMR (300 MHz, DMSO-d6): d
0.75 (d, 3H, J = 6.7 Hz, CH3), 1.15 (d, 3H, J = 7.0 Hz, CH3), 2.80–2.93 (m, 1H,
CH(CH3)2), 4.63 (dd, 1H, J = 11.4, 10.5 Hz, CHA2 ), 4.80 (dd, 1H, J = 11.4, 4.7 Hz,
CHB2), 5.17 (d, 1H, J = 18.2 Hz, Ph–CH2A), 5.22 (d, 1H, J = 18.2 Hz, Ph–CHB2), 6.06–
6.15 (m, 1H, CH–CH2), 7.25–7.47 (m, 5H, arom. H – phenyl), 8.13 (dd, 1H,
J = 7.9, 7.6 Hz, arom. H), 8.35 (dd, 1H, J = 8.5, 7.3 Hz, arom. H), 8.52 (d, 1H,
J = 8.2 Hz, arom. H), 8.62 (d, 1H, J = 8.5 Hz, arom. H). 13C NMR (75 MHz,
DMSO-d6): d 14.6, 18.7, 30.0, 45.8, 46.8, 69.5, 105.0, 118.5, 128.4, 128.5, 128.7,
129.1, 131.9, 133.6, 135.2, 136.2, 139.0, 140.4, 143.6, 147.6, 158.2. Anal. Calcd
for C22H21ClN4O2ꢂ2H2O (444.93): C, 59.39; H, 5.66; N, 12.59. Found: C, 59.47;
H, 5.31; N, 12.58.
Acknowledgement
25. Shinkai, S.; Nakao, H.; Tsuno, T.; Manabe, O.; Ohno, A. Chem. Commun. 1984,
849.
26. Hydroperoxide 4b-OOH was prepared in an NMR tube by dissolving salt 4b
The authors wish to thank the Czech Science Foundation (Grant
No. 203/07/1246) for financial support.
(10 mg; 0.029 mmol) in CD3CN (600 lL) and adding urea–H2O2 complex
(12 mg; 0.127 mmol) and anhydrous K2CO3 (20 mg; 0.145 mmol). The mixture
was sonicated for 10 min before analysis. 1H NMR (600 MHz, CD3CN): major
Supplementary data
isomer
d 0.15 (d, 3H, J = 6.8 Hz, CH3), 0.94 (d, 3H, J = 6.9 Hz, CH3), 2.20
(overlapped m, 1H, CH(CH3)2), 3.23 (s, 3H, N–CH3), 3.95 (dd, 1H, J = 11.5, 7.8 Hz,
CHA2 ), 4.02 (dd, 1H, J = 11.5, 1.7 Hz, CHB2), 4.63 (overlapped m, 1H, CH–N), 7.06
(dd, 1H, J = 7.4, 7.3 Hz, arom. H), 7.14 (dd, 1H, J = 8.2, 8.2 Hz, arom. H), 7.43 (dd,
1H, J = 7.4, 7.3 Hz, arom. H), 7.71 (d, 1H, J = 7.9 Hz, arom. H); minor isomer: d
0.90 (d, 3H, J = 6.9 Hz, CH3), 1.12 (d, 3H, J = 7.0 Hz, CH3), 2.41 (sept, 1H,
J = 7.0 Hz, CH(CH3)2), 3.19 (s, 3H, N–CH3), 3.64 (dd, 1H, J = 10.4, 2.0 Hz, CHA2 ),
3.71 (dd, 1H, J = 10.4, 3.5 Hz, CHB2), 4.17 (m, 1H, CH–N), 6.98 (dd, 1H, J = 8.1,
7.9 Hz, arom. H), 7.11 (d, 1H, J = 8.4 Hz, arom. H), 7.40 (dd, 1H, J = 8.6, 8.6 Hz,
arom. H), 7.63 (dd, 1H, J = 7.9, 1.2 Hz, arom. H). 13C NMR (150.9 MHz, CD3CN):
major isomer d 13.5 (CH3), 18.7 (CH3), 27.7 (CH(CH3)2), 28.6 (N–CH3), 42.7
(CH2), 62.6 (CH–CH2), 85.5 (C–OOH), 117.4, 121.2, 130.1 and 132.1 (arom. CH),
132.6 and 135.2 (arom. quat. C), 149.3 and 161.6 (CO); minor isomer d CH3 and
(CH(CH3)2) signals are overlapped with signals of the major species, 28.3 (N–
CH3), 45.8 (CH2), 66.1 (CH–CH2), 86.9 (C–OOH), 114.2, 120.3, 130.1 and 132.1
(arom. CH), 131.8 and 135.3 (arom. quat. C), 150.2 and 162.8 (CO). HR-MS:
(M+H+) calcd: 331.14008; found: 331.14062.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.12.096.
References and notes
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