Unexpected epoxidation product in oxidation of N-tosyl-7-methoxy-1,3a,4,8b-tetrahydrocyclopenta[b]indole with potassium permanganate

Article abstract of DOI:10.1016/j.mencom.2009.09.019

An unexpected product of N-tosyl-7-methoxy-1,3a,4,8b-tetrahydrocyclopenta[b]indole oxidation with potassium permanganate under alkaline conditions was isolated. Along with (2R,3S,3aR,8bS)-N-tosyl-7-methoxy-2,3-dihydroxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole, (3SR,3aRS,8bSR)-N-tosyl-7-methoxy-3-hydroxy-1,2-epoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole was formed.

Full text of DOI:10.1016/j.mencom.2009.09.019

Mendeleev
Communications
Mendeleev Commun., 2009, 19, 284–286
Unexpected epoxidation product in oxidation of N-tosyl-7-methoxy-
1,3a,4,8b-tetrahydrocyclopenta[b]indole with potassium permanganate
Rail R. Gataullin*a and Kyrill Yu. Suponitsky*b
a Institute of Organic Chemistry, Ufa Scientific Centre of the Russian Academy of Sciences, 450054 Ufa,
Russian Federation. Fax: +7 347 235 6066; e-mail: gataullin@anrb.ru
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5085; e-mail: kirshik@yahoo.com
DOI: 10.1016/j.mencom.2009.09.019
An unexpected product of N-tosyl-7-methoxy-1,3a,4,8b-tetrahydrocyclopenta[b]indole oxidation with potassium permanganate
under alkaline conditions was isolated. Along with (2R,3S,3aR,8bS)-N-tosyl-7-methoxy-2,3-dihydroxy-1,2,3,3a,4,8b-hexahydro-
cyclopenta[b]indole, (3SR,3aRS,8bSR)-N-tosyl-7-methoxy-3-hydroxy-1,2-epoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole was
formed.
The oxidation of alkenes with potassium permanganate is
frequently used for the synthesis of cis-diols and oxygen-
containing organic compounds.1 An extensive study on the
oxidative transformation with this reagent revealed almost all
possible reaction products.2 Generally, a vicinal cis-diol is the
final product of olefin oxidation by KMnO4 under alkaline
conditions. The conditions for carboxylic acid formation upon
treatment of an olefin with this oxidant are also well known.1–3
Only few examples of olefin epoxidation with potassium per-
manganate can be found in the literature.4,5 Epoxide formation
in the reaction of KMnO4 with tetrafluoroethylene in anhydrous
HF at –78 °C was described. This reaction results in a mixture
of tetrafluoroethylene oxide and its isomerisation product – tri-
fluoroacetic acid fluoroanhydride.4 The allylic oxidation of
olefins with peracetic acid catalyzed by di(trifluoromethane-
sulfono)[1,4-dimethyl-7-(pyridin-2-ylmethyl)-1,4,7-triazonan]-
manganese [Mn(CF3SO3)2(H,MePyTACN)] is also known (though
the yeild is lower than 1%). However, in this case, manganese
does not exist in the form of the permanganate ion.5 The
oxidation of cycloalkenones with KMnO4 in the presence of
carboxylic acids, which results in α-carboxyl alkyl substituted
cycloalkenone formation with the retention of double bonds,
should also be mentioned.6–8
by comparison of the spectral data† with those obtained earlier
for similar compounds.9
The reaction of 5 with KMnO4 in MeCN/MeOH/H2O results
in a complex mixture of products. We suppose that it consists
of diols 6, 7 and epihydrine 8. Our attempts to separate this
mixture chromatographically were unsuccessful. The mixture
1
thus obtained displays an H NMR spectrum similar to that of
the initial reaction mixture with unresolved signals of protons.
The reaction of compounds 6–8 with isopropenyl acetate in
CH2Cl2 in the presence of the catalytic amounts of TsOH resulted
in their O-acetates 9–11, which were isolated by chromato-
graphy on silica gel.‡
†
The 1H and 13C NMR spectra were measured on a Bruker AM-300
spectrometer (300.13 and 75.47 MHz in CDCl3). The internal standard
was TMS. The elemental analysis was carried out using an M-185B
Analyzer. Column chromatography was carried out on silica gel (Lankaster
LS 40/100 μm). For qualitative analysis, we used TLC plates Sorbfil
(Sorbpolimer, Russia) with the detection of substances with I2.
4: A mixture of tosylate 3 (5 g, 14.6 mmol), I2 (6.71 g, 26.4 mmol),
NaHCO3 (20.3 g) in CH2Cl2 (150 ml) was stirred for 24 h at 20 °C.
CH2Cl2 (100 ml) was then added to the reaction mixture, treated with
10% Na2S2O3 solution (3×100 ml), water (100 ml) and dried with Na2SO4.
The solvent was evaporated in vacuo. The crystallization of the residue
from EtOH led to the precipitation of a dark thick crystalline mass. By
this reason, the residue was chromatographed on silica gel (70 g), Rf 0.4.
The yield was 2.4 g (35.6%), mp 147–149 °C (dark crystals from EtOH).
1H NMR, d: 1.70–2.60 (m, 4H, 2CH2), 2.35 (s, 3H, Me), 3.65 (t, 1H,
N
H
H8b, JH8b
8.4 Hz, JH8b 8.4 Hz), 3.75 (s, 3H, OMe), 4.73 (d, 1H, H3a,
,H3a
N
N
,H1A
Mn
OTf
OTf
J 8.4 Hz), 4.87 (d, 1H, H3, J 3.9 Hz), 6.60 (d, 1H, H8, J 1.5 Hz), 6.73
(dd, 1H, H6, J1 1.5 Hz, J2 8.9 Hz), 7.22 (m, 2H, J 8.3 Hz), 7.53 (d, 1H,
H5, J 8.9 Hz), 7.61 (d, 2H, HAr, J 8.3 Hz). Found (%): C, 48.41, H, 4.12,
I, 26.81, N, 2.75, S, 6.65. Calc. for C19H20INO3S (%): C, 48.62, H, 4.30,
I, 27.04, N, 2.98, S, 6.83.
Me
N
Me
Mn(CF3SO3)2(H,MePyTACN)
In order to synthesize 2,3-dihydroxy-substituted 1,2,3,3a,4,8b-
hexahydrocyclopenta[b]indole, we have carried out the oxi-
dation of 1,3a,4,8b-tetrahydrocyclopenta[b]indole by KMnO4.
However, this reaction resulted in the formation of an unusual
product, namely, (1aR,2S,2aR,7bS,7cR)-6-methoxy-3-(4-methyl-
phenylsulfonyl)-1a,2,2a,3,7b,7c-hexahydrooxireno[2',3':3,4]cyclo-
penta[b]indol-2-ol.
The reaction of compound 2 with TsCl gives tosylate 3,
which reacts with I2 in methylene chloride leading to indoline
4. The boiling of 4 in an excess of pyperidine results in tetra-
hydrocyclopenta[b]indole 5 formation in a good yield. The
structure of the product is confirmed by elemental analysis and
5: Derivative 4 (2.4 g, 5.1 mmol) was dissolved in pyperidine (20 ml)
and heated under pyperidine boiling for 6 h. The solvent excess was
evaporated in vacuo, dissolved in CH2Cl2 (250 ml), washed with 5% HCl
solution and then twice with water. The organic phase was dried with
MgSO4, the solvent was evaporated in vacuo, the residue was crystallized
from EtOH. The yield was 1.57 g (90%), mp 124 °C. 1H NMR, d:
2.38 (s, 3H, Me), 2.45 (d, 1H, H1A, Jgem 17.0 Hz), 2.79 (ddq, 1H,
H1B, Jgem 17.0 Hz, J2 8.3 Hz, J3 1.9 Hz), 3.46 (dd, 1H, H8b, J1 8.0 Hz,
J2 8.3 Hz), 3.80 (s, 3H, OMe), 5.22 (dd, 1H, H3a, J1 1.9 Hz, J2 8.0 Hz),
5.82–5.90 (m, 2H, H2, H3), 6.60 (d, 1H, H8, J 2.5 Hz), 6.77 (dd, 1H, H6,
J1 2.5 Hz, J2 8.8 Hz), 7.15 (d, 2H, J 8.0 Hz), 7.50–7.59 (m, 3H). Found
(%): C, 66.67; H, 5.45; N, 3.93; S, 9.19. Calc. for C19H19NSO3 (%): C,
66.84; H, 5.61; N, 4.10; S, 9.39.
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© 2009 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2009, 19, 284–286
Cl
MeO
MeO
TsCl/Py
NH2
NH2
1
2
MeO
MeO
1
H
H
MeO
8
pyperidine
I2
8b
8b
3a
6
3a
5
3
4
4
CH2Cl2,
NaHCO3,
20 °C
reflux,
5–6 h
NHTs
N
N
Ts
5
I
H
H
3
Ts
4
MeO
MeO
MeO
O
H
H
H
OH
OH
OH
KMnO4
+
+
MeCN, MeOH,
H2O, 20 °C
N
N
N
OH
OH
H
H
H
Ts
Ts
Ts
6
7
8
MeO
MeO
MeO
O1
1
7c
H
H
H
2
8
7
OAc
OAc
OAc
7
6
IPA
1a
2
8b
3a
8b
7b
2a
8a
7a
+
+
4
3
3
CH2Cl2, TsOH
3
N
4
N
4
N
3a
OAc
OAc
H
H
H
Ts
Ts
Ts
9
10
11
The structures of compounds 10 and 11 were determined
‡
Oxidation method. To a solution of 5 (1.4 g, 4.1 mmol) in 30 ml of
by single crystal X-ray crystallography. All our attempts to
grow single crystals of isomer 9 suitable for an X-ray study
were unsuccessful. Its structure was determined by the elemental
analysis and spectral methods.
MeCN and 7 ml of MeOH, 3.55 g KMnO4 (as solution in 5 ml of water)
was added. This led to intense warming-up of the reaction mixture. After
that, reaction mixture was stirred at room temperature for 3 h. The residue
was filtered off, washed with CH2Cl2, and the organic solvents were
evaporated. The residue was diluted with 25 ml of H2O, the water layer
was saturated with NaCl, extracted with CH2Cl2, dried with Na2SO4, and
the solvent was evaporated in vacuo. The compound mixture was purified
with silica gel; the eluent was CH2Cl2. This attempt was unsuccessful.
Therefore, the mixture (1.1 g) was dissolved in 10 ml of CH2Cl2, and
then isopropenyl acetate (4 ml) and para-toluenesulfonic acid (40 mg)
were added; the mixture was stirred, the reaction was controlled using
TLC (eluent, benzene–EtOAc, 4:1). After the reaction was completed,
10 ml of H2O were added and the mixture was extracted with CH2Cl2
(70 ml). The organic layer was washed with H2O and dried with Na2SO4.
The solvent was evaporated in vacuo. In order to isolate compounds
9–11, the residue was chromatographed on silica gel (30 g), eluted with
benzene. After compound 9 was passed from the column, 5% ethyl
acetate was added to the eluent. Epoxide 11, and after that compound 10
were isolated.
The ORTEP views of 10 and 11 are shown in Figure 1.§ An
asymmetric unit cell of both compounds contains one molecule.
Some differences in the molecular geometries of 10 and 11 are
observed. The central dihydropyrrole ring is planarized in both
molecules: it is planar in 10 [mean deviation is 0.008(3) Å]
while in 11, it adopts planarized envelope geometry with the
C(3A) atom slightly moved out [by 0.204(3) Å] of the plane of
four remaining atoms. The orientations of the p-tolylsulfonyl
group are somewhat different by the inclination of the S(1)–N(4)
bond relative to the dihydropyrrole ring. More pronounced dif-
ferences are found for the remaining part of the molecules. In
10, the cyclopentane fragment adopts an envelope conforma-
tion, while it is in a planarized twist form in 11, which is due to
the influence of the rigid epoxy group. In both molecules, the
substituents of the cyclopentane fragment are trans oriented to
the dihydropyrrole ring. The crystal structures of both compounds
are stabilized by ordinary van der Waals and weak C–H···O
interactions.
1
9: Yield 0.05 g (3%), amorphous solid. H NMR, d: 1.35, 1.50, 2.40
(s, 3H, 3Me), 1.75 (ddd, 1H, H1A, J1 2.2 Hz, J2 8.7 Hz, Jgem 13.6 Hz),
2.30–2.45 (m, 1H, H1B), 3.70 (q, 1H, H8b, J 8.7 Hz), 3.75 (s, 3H, OMe),
4.20 (d, 1H, H3a, J 8.7 Hz), 4.71 (dt, 1H, H2, J1 2.2 Hz, J2 5.5 Hz),
5.13 (d, 1H, H3, J 5.5 Hz), 6.55 (d, 1H, H8, J 2.5 Hz), 6.75 (dd, 1H,
H6, J1 2.5 Hz, J2 8.8 Hz), 7.22 (d, 2H, HAr, J 8.1 Hz), 7.60 (d, 1H, H5,
J 8.8 Hz), 7.69 (d, 2H, HAr, J 8.1 Hz). Found (%): C, 59.97; H, 5.37;
N, 2.94; S, 6.81. Calc. for C23H25NO7S (%): C, 60.12; H, 5.48; N, 3.05;
S, 6.98.
(1aR,2S,2aR,7bS,7cR)-6-Methoxy-3-(4-methylphenylsulfonyl)-1a,2,2a,
3,7b,7c-hexahydrooxireno[2',3':3,4]cyclopenta[b]indol-2-yl acetate 11:
1
yield 0.15 g (8.8%), mp 165 °C (EtOH). H NMR, d: 2.20 (s, 3H, Me),
10: Yield 0.3 g (16%). 1H NMR (CDCl3) d: 1.98 (dt, 1H, H1A, J1 4.6 Hz,
Jgem 13.7 Hz), 2.05, 2.13, 2.38 (s, 3H, 3Me), 2.30 (ddd, 1H, H1B, J1 4.6 Hz,
J2 9.6 Hz, Jgem 13.7 Hz), 3.53 (dt, 1H, H8b, J1 4.6 Hz, J2 9.6 Hz), 3.75
(s, 3H, Me), 4.53 (dd, 1H, H3a, J1 4.6 Hz, J2 9.6 Hz), 5.19 (q, 1H, H2,
J 4.6 Hz), 5.34 (t, 1H, H3, J 4.6 Hz), 6.55 (d, 1H, H8, J 2.4 Hz), 6.78 (dd,
1H, H6, J1 2.4 Hz, J2 8.9 Hz), 7.19 (d, 2H, HAr, J 8.0 Hz), 7.54 (m, 3H,
2.35 (s, 3H, Me), 3.51 (d, 1H, H7b, J 7.7 Hz), 3.63 (d, 1H, H7c, J 2.8 Hz),
3.69 (dd, 1H, H1a, J1 1.7 Hz, J2 2.8 Hz), 3.78 (s, 3H, OMe), 4.28 (dd,
1H, H2a, J1 4.6 Hz, J2 7.7 Hz), 5.26 (dd, 1H, H2, J1 1.7 Hz, J2 4.6 Hz),
6.64 (dd, 1H, H7, J1 0.9 Hz, J2 2.6 Hz), 6.85 (ddd, 1H, H5, J1 0.6 Hz,
J2 2.6 Hz, J3 8.9 Hz), 7.17 (d, 2H, HAr, J 8.0 Hz), 7.43 (d, 2H, HAr
,
J 8.0 Hz), 7.61 (d, 1H, H4, J 8.9 Hz). 13C NMR, d: 20.8, 21.4, 55.6 (3Me),
46.5 (C7b), 56.4, 57.8 (C7c, C1a), 67.5 (C2a), 80.7 (C2), 110.1, 114.2 (C4,
C5), 120.4 (C7), 127.2, 129.5 (C2', C6', C3', C5'), 132.1, 133.9, 135.1 (C3a,
C7a, C4'), 144.1 (C1'), 157.9 (C6), 170.7 (C=O). Found (%): C, 60.53; H,
4.92; N, 3.14; S, 7.55. Calc. for C21H21NO6S (%): C, 60.71; H, 5.09;
N, 3.37; S, 7.72.
H
Ar). 13C NMR, d: 20.6, 20.7, 21.4 (3Me), 35.0 (C1), 40.4 (C8b), 55.5
(Me), 68.8, 72.3, 77.8 (C3a, C3, C2), 109.9, 113.5, 117.9 (C5, C6, C8),
127.2, 129.5 (C2', C6', C3', C5'), 133.9, 134.1, 136.8, 144.0 (C4a, C7, C1', C4'),
157.6 (C7), 169.6, 169.7 (2C=O). Found (%): C, 59.98; H, 5.30; N, 2.88;
S, 6.82. Calc. for C23H25NO7S (%): C, 60.12; H, 5.48; N, 3.05; S, 6.98.
– 285 –

Mendeleev Commun., 2009, 19, 284–286
Because the oxidation of the double bond of compound 5
proceeds with simultaneous reduction of permanganate to MnO2,
this MnO2 should act as a reagent for an allylic oxidation. The
intramolecular transformation of this product can lead to inter-
mediate A, which can be transformed into epoxide B, and after
that into compound 8 under alkaline conditions. The examples
of the specific influence of sulfonyl groups in some reactions of
olefins with elecrtophilic reagents with their direct participation
in these transformations are known.11
C(20)
O(7)
C(7)
C(8)
C(8A)
C(1)
O(1)
C(6)
C(5)
C(8B)
C(10)
C(2)
C(3)
C(4A)
N(4)
C(9)
O(2)
C(17)
C(16)
C(3A)
C(18)
C(13)
C(11)
Me
O(3)
C(19)
OH
C(12)
MeO
H
S(1)
O(4)
O(6)
C(15)
OH
O
C(14)
O(5)
O
S
MeO
10
N
OH
H
H
H OH
Ts
N
allylic oxidation product
MeO
C(18)
O(6)
A
C(8)
C(7)
C(6)
O
H
C(1)
C(17)
O(1)
C(14)
C(8B)
OH–
C(13)
C(5)
O(4)
C(4A)
C(3A)
N
8
OH
C(12)
O
H
– H2O
C(15)
C(2)
C(3)
S
OH
OH
C(16)
N(4)
C(11)
S(1)
O(2)
C(9)
Me
O(5)
B
O(3)
C(10)
This work was supported by the Federal Programme on the
Support of Leading Scientific Schools (grant no. SSH-3019.2008.3).
11
Figure 1 ORTEP view of compounds 10 and 11. Thermal displacement
ellipsoids are drawn at the 50% probability level.
References
1
A. H. Hains, Methods for the Oxidation of Organic Compounds, Academic
Press, London, 1985.
S. Dash, S. Patel and B. K. Mishra, Tetrahedron, 2009, 65, 707.
A. G. Fatiadi, Synthesis, 1987, 85.
G. G. Belen’kii, L. S. German and I. L. Knunyants, Izv. Akad. Nauk
SSSR, Ser. Khim., 1968, 554 (Bull. Acad. Sci. USSR, Div. Chem. Sci.,
1968, 17, 538).
A. Garcia-Bosh, A. Company, X. Fontrodona, X. Ribas and M. Costas,
Org. Lett., 2008, 10, 2095.
A. S. Demir and H. Findik, Tetrahedron, 2008, 64, 6196.
C. Tanyeli, A. Tosun, E. Turkut and B. Sezen, Tetrahedron, 2003, 59,
1055.
M. G. Vinogradov, S. P. Verenchikov, T. M. Fedora and G. I. Nikishin,
Zh. Org. Khim. 1975, 11, 947 (in Russian).
R. R. Gataullin, R. R. Ishberdina, O. V. Shitikova, F. F. Minnigulov, L. V.
Spirikhin and I. B. Abdrakhmanov, Khim. Geterotsikl. Soedin., 2006,
1184 [Chem. Heterocycl. Compd. (Engl. Transl.), 2006, 42, 1025].
It is well known that the heating of cyclohexene with MnO2
in acetic acid at 110 °C for 2 h leads to the allylic oxidized
product – cyclohex-2-enyl acetate in 66% yield. However, this
reaction requires the presence of 10 mol% potassium bromide.10
2
3
4
§
The single crystals of compounds 10 and 11 suitable for the X-ray
5
study were grown by the slow crystallization from 95% ethanol. Reflec-
tions for compounds 10 and 11 were collected on a SMART APEX2 CCD
diffractometer [l(MoKα) = 0.71073 Å, graphite monochromator, w-scans]
at 100 K. The structures were solved by the direct methods and refined
by the full-matrix least-squares procedure against F2 in anisotropic approxi-
mation. All the hydrogen atoms were placed in geometrically calculated
positions and refined within a riding model.
For 10 (C23H25O7NS): monoclinic, space group P21/c: a = 16.142(3),
b = 6.9301(13) and c = 19.846(3) Å, b = 92.617(4)°, V = 2217.8(7) Å3,
Z = 4, M = 459.50, dcalc = 1.376 g cm–3, m = 0.191 mm–1, F(000) = 968,
wR2 = 0.1197, GOF = 0.982 for 4350 independent reflections with 2q < 52°,
R1 = 0.0632 for 2151 reflections with I > 2s(I).
6
7
8
9
10 J. R. Gilmore and J. M. Moller, Chem. Commun. C, 1971, 2355.
11 J. I. G. Cadogan, D. K. Cameron, I. Gosney, R. M. Highcock and S. F.
Newlands, J. Chem. Soc., Chem. Commun., 1986, 766.
For 11 (C21H21O6NS): monoclinic, space group C2/c: a = 30.595(2),
b = 8.3348(5) and c = 20.6251(11) Å, b = 131.8850(10)°, V = 3915.6(4) Å3,
Z = 8, M = 415.45, dcalc = 1.409 g cm–3, m = 0.205 mm–1, F(000) = 1744,
wR2 = 0.0960, GOF = 1.041 for 4689 independent reflections with 2q < 56°,
R1 = 0.0422 for 3736 reflections with I > 2s(I).
CCDC 742874 and 742875 contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2009.
Received: 30th March 2009; Com. 09/3309
– 286 –