Reaction of α-bromolevoglucosenone with 2,2-disubstituted 1,3-dinitropropanes

Article abstract of DOI:10.1134/S1070428012030219

2,2-Bis(nitromethyl)decane and 4-methyl-2,2-bis(nitromethyl)pentane reacted with α-bromolevoglucosenone in the presence of a base under ultrasonic treatment to give the corresponding cyclopenta-fused derivatives. Analogous reactions of 1,1-bis(nitromethyl

Full text of DOI:10.1134/S1070428012030219

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 3, pp. 456–459. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © L.Kh. Faizullina, M.M. Iskakova, A.A. Pershin, Sh.M. Salikhov, M.G. Safarov, F.A. Valeev, 2012, published in Zhurnal
Organicheskoi Khimii, 2012, Vol. 48, No. 3, pp. 455–458.
Reaction of α-Bromolevoglucosenone
with 2,2-Disubstituted 1,3-Dinitropropanes
L. Kh. Faizullinaa, M. M. Iskakovaa, A. A. Pershina, Sh. M. Salikhovb,
M. G. Safarova, and F. A. Valeevb
a Bashkir State University ul. Zaki Validi 32, Ufa, 450074 Bashkortostan, Russia
e-mail: lfajzullina@yandex.ru
b Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
Received July 18, 2011
Abstract—2,2-Bis(nitromethyl)decane and 4-methyl-2,2-bis(nitromethyl)pentane reacted with α-bromolevo-
glucosenone in the presence of a base under ultrasonic treatment to give the corresponding cyclopenta-fused
derivatives. Analogous reactions of 1,1-bis(nitromethyl)cycloalkanes with α-bromolevoglucosenone afforded
spiro compounds.
DOI: 10.1134/S1070428012030219
Reactions of α-bromo and α-iodo derivatives of
conjugated enones with 2,2-dimethyl-1,3-dinitropro-
pane lead to the formation of 2,3-cyclopentaannulation
products containing a nitro group and geminal methyl
groups in the cyclopentane fragment [1, 2]. Our
attempts to obtain analogous products by treatment of
α-bromolevoglucosenone with monosubstituted dinitro
compounds or those having no other substituents than
nitro groups were unsuccessful [3]. Nevertheless, with
a view to extend the scope of application of this trans-
formation, cyclopentaannulation of α-halo-substituted
levoglucosenones can be achieved using other 2,2-di-
substituted 1,3-dinitropropanes.
By reacting the corresponding ketones with nitro-
methane in diethylamine we synthesized 2,2-bis(nitro-
methyl)decane, 4-methyl-2,2-bis(nitromethyl)pentane,
1,1-bis(nitromethyl)cyclohexane, 1,1-bis(nitromethyl)-
cyclopentane, and 1,1-bis(nitromethyl)cyclododecane
[4]. Ultrasonic treatment of a solution of α-bromolevo-
glucosenone and 2,2-bis(nitromethyl)decane in toluene
in the presence of potassium carbonate and a catalytic
amount of dicyclohexano-18-crown-6 afforded stereo-
isomeric tricyclic 3,4-cyclopentaannulation products
IIa and IIb. Analogous reaction with 4-methyl-2,2-bis-
(nitromethyl)pentane gave a mixture of epimers IIIa
and IIIb (Scheme 1).
1,3-dinitropropane dianions [2]; their addition to
α-bromolevoglucosenone is influenced by steric inter-
actions between the 1,6-anhydro bridge in the substrate
and geminal substituents in the reagent. Unsuccessful
cyclopentaannulation of α-halolevoglucosenone may
be rationalized in terms of the possibility for charge
delocalization in carbanions derived from 1,3-dinitro
derivatives having no geminal substituents. Unlike
isomer mixture IIIa/IIIb which was difficult to sepa-
rate, epimers IIa and IIb can be readily separated
by chromatography on silica gel. The reaction of
α-bromolevoglucosenone (I) with cyclic dinitropro-
panes resulted in the formation of spiro compounds
IV–VI in high yield (Scheme 1).
The structure of compounds II–VI and configura-
tion of new chiral centers therein were determined by
1H and 13C NMR spectroscopy, including HSQC,
HMBC, and NOESY experiments performed with
1
compounds IIa and IIb. In the H NMR spectrum of
isomer IIa the 2-H signal appeared as a doublet of
doublets at δ 3.74 ppm (3J2,3 = 9.9, 4J2,5 = 2.7 Hz), and
the 3-H proton resonated as a doublet at δ 4.91 ppm
(3J2,3 = 9.9 Hz). The corresponding couplings were
confirmed by correlations observed in the HH COSY
3
spectrum. The large value of J2,3 (9.9 Hz) indicated
trans orientation of 2-H and 3-H; taking into account
the lack of coupling between 1-H and 2-H, the new
asymmetric center (C2) in epimers IIa and IIb was
The formation of diastereoisomers IIa/IIb and
IIIa/IIIb suggests intermediacy of 2,2-disubstituted
456

REACTION OF α-BROMOLEVOGLUCOSENONE
457
Scheme 1.
O2N
O2N
O2N
Me
9
O
10
O
O
O
O
O2N
11
O
Me
C8H17
O
O
O
H
H
H
1
O2N
Me
Me
Me
47%
O2N
O2N
8
7
2
+
1''
Me
1'C–88' H17
3
4
65%
6
Me
Me
Me
O
Br
O
O
5
C8H17
IIIa, IIIb (2:1)
I
IIa
(2:1)
IIb
NO2
NO2
( )n
O
O
H
O2N
O
( )n
IV–VI
IV, n = 1, yield 96%; V, n = 2, 56%; VI, n = 8, 64%.
assigned 2R and 2S configuration, respectively. Orien-
tation of the 4-CH3 group in IIa and IIb was deter-
mined on the basis of the NOESY data. The NOESY
spectrum of IIa displayed correlations between 3-H
and 1″-H, as well as between 2-H and 1′-H; therefore,
the 4-CH3 group is oriented syn with respect to 3-H,
and the 4-octyl substituent is oriented syn with respect
to 2-H. The presence of 3-H–1′-H and 2-H–1″-H cor-
relation peaks in the NOESY spectrum of epimer IIb
indicated syn orientation of the 4-CH3 group and 2-H
and trans orientation of the octyl substituent.
tography on silica gel L (40–100 μm); 30–100 g of the
sorbent per gram of substrate. The elemental com-
positions were determined on a Euro-2000 CHNS(O)
analyzer. Initial (–)-(1S,2R,3RS,5R)-3-bromo-6,8-di-
oxabicyclo[3.2.1]oct-2-en-4-one (I, α-bromolevo-
glucosenone) was synthesized as described in [1].
2,2-Bis(nitromethyl)decane, 4-methyl-2,2-bis(ni-
tromethyl)pentane, and 1,1-bis(nitromethyl)cyclo-
alkanes (general procedure). A solution of 0.001 mol
of the corresponding ketone and 0.0015 mol of nitro-
methane in 0.005 mol of diethylamine was kept for
15–50 days at room temperature (TLC). When the re-
action was complete, the mixture was treated with 2 N
hydrochloric acid and extracted with ethyl acetate
(3×50 ml). The combined extracts were washed with
a saturated solution of sodium hydrogen carbonate
(10 ml) and dried over MgSO4, the solvent was
distilled off, and the residue was purified by column
chromatography on silica gel [4].
Reaction of α-bromolevoglucosenone (I) with
2,2-disubstituted 1,3-dinitropropanes. α-Bromolevo-
glucosenone (I), 0.001 mol, was dissolved in 10 ml of
toluene, 0.0012 mol of the corresponding 2,2-disubsti-
tuted 1,3-dinitropropane, 0.006 mol of potassium car-
bonate, and a catalytic amount of dicyclohexano-18-
crown-6 were added at room temperature. The mixture
was subjected to ultrasonic treatment over a period of
1 h (TLC monitoring), the solvent was distilled off,
and the residue was subjected to column chromatog-
raphy on silica gel.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
a Bruker AM-300 spectrometer at 300 and 75.47 MHz,
respectively, as well as on a Bruker Avance III instru-
1
ment (500 MHz for H); chloroform-d was used as
solvent, and tetramethylsilane, as internal reference.
The optical rotations were measured on a Perkin Elmer
141 polarimeter. The melting points were determined
on a Kofler S 30A/G hot stage (DDR). The mass spec-
tra (atmospheric pressure chemical ionization) were
obtained on a Shimadzu-2010EV GC–MS system. The
reaction mixtures were subjected to ultrasonic treat-
ment using a UZDN-2T instrument (44 Hz, 80 mA).
Analytical thin-layer chromatography was performed
on Sorbfil PTSKh-AF-A plates; spots were developed
by treatment with a solution of 4-methoxybenzalde-
hyde. The products were isolated by column chroma-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

FAIZULLINA et al.
458
(1S,2R,3S,4R,8R)- and (1S,2R,3S,4S,8R)-4-
51.72 (C4), 70.78 (C10), 73.48 (C1), 98.32 (C3), 99.54
(C8), 130.76 (C6), 148.01 (C5), 188.16 (C=O).
Methyl-4-octyl-3-nitro-9,11-dioxatricyclo[6.2.1.02,6]-
undec-5-en-7-ones IIa and IIb. Yield 47%. Colorless
crystals, mp 51–54°C.
1
(4S)-Epimer IIIb. H NMR spectrum, δ, ppm:
3
0.92 d and 1.01 d (3H each, Me2CH, J = 6.6 Hz),
2
(4R)-Epimer IIa. Rf 0.6 (petroleum ether–ethyl
acetate, 3:1). [α]D20 = –132° (c = 1.35, CHCl3). 1H NMR
spectrum, δ, ppm: 0.85 t (3H, 8′-H, 3J = 7.1 Hz), 1.10 s
(3H, 1″-H), 1.28 m (12H, CH2), 1.76 m (2H, Me),
1.09 s (3H, 4-CH3), 1.26 d.d (1H, 4-CH2, J = 13.6,
3J = 4.9 Hz), 1.71 m (1H, 4-CH2), 1.82 m (1H,
3
4
Me2CH), 3.71 d.d (1H, 2-H, J2, 3 = 10.3, J2, 5
=
2
3
2.7 Hz), 3.86 d.d (1H, 10-H, J = 7.3, J = 4.4 Hz),
3
4
4.0 d (1H, 10-H, 2J = 7.3 Hz), 4.73 d (1H, 1-H, 3J1,10
=
3.74 d.d (1H, 2-H, J2,3 = 9.9, J2,5 = 2.7 Hz), 3.87 d
2
3
3
(1H, 10-H, J = 7.3, J = 4.3 Hz), 4.00 d (1H, 10-H,
4.4 Hz), 4.96 d (1H, 3-H, J = 10.3 Hz), 5.21 s (1H,
8-H), 6.64 d (1H, 5-H, 4J5,2 = 2.7 Hz). 13C NMR spec-
trum, δC, ppm: 19.03 (Me), 23.99 (Me), 24.82
(CHMe2), 24.89 (Me), 46.64 (4-CH2), 46.95 (C2),
51.92 (C4), 70.89 (C10), 73.63 (C1), 94.11 (C3), 99.50
(C8), 130.76 (C6), 147.54 (C5), 188.17 (C=O). Mass
spectrum, m/z: 282 [M + H]+, 280 [M – H]–. Found, %:
C 59.10; H 6.54; N 4.11. C14H19NO5. Calculated, %:
C 59.72; H 6.75; N 4.98.
2J = 7.3 Hz), 4.72 d (1H, 1-H, J1,10 = 4.3 Hz), 4.91 d
3
3
(1H, 3-H, J = 9.9 Hz), 5.21 s (1H, 8-H), 6.57 d (1H,
5-H, J5, 2 = 2.7 Hz). 13C NMR spectrum, δC, ppm:
4
14.11 (Me), 18.30 (Me), 22.64 (CH2), 24.86 (CH2),
29.21 (CH2), 29.41 (CH2), 29.89 (CH2), 31.82 (CH2),
38.29 (CH2), 47.32 (C2), 52.05 (C4), 70.90 (C10), 73.59
(C1), 93.97 (C3), 99.48 (C8), 131.25 (C6), 146.70 (C5),
188.18 (C=O).
(4S)-Epimer IIb. Rf 0.5 (petroleum ether–ethyl
acetate, 3:1). [α]D20 = –127° (c = 0.15, CHCl3). 1H NMR
spectrum, δ, ppm: 0.87 t (3H, 8′-H, J = 7.2 Hz),
(1′S,2′R,3′S,8′R)-3′-Nitrospiro[cyclopentane-
1,4′-[9,11]dioxatricyclo[6.2.1.02,6]undec]-5′-en-7′-
one (IV). Yield 60%, colorless crystals, mp 126–
128°C, Rf 0.42 (petroleum ether–ethyl acetate, 3:1),
[α]D20 = –104.3° (c = 0.4, CHCl3). 1H NMR spectrum, δ,
ppm: 1.62 m (4H, 2′-H, 3′-H), 1.80 m (2H, 1′-H, 4′-H),
1.95 m (1H, 4′-H), 2.21 m (1H, 1′-H), 3.67 d.d (1H,
3
1.22 m (12H, CH2), 1.49 s (3H, 1″-H), 1.56 m (2H,
3
4
CH2), 3.72 d.d (1H, 2-H, J23,3 = 10.1, J2,5 = 2.7 Hz),
2
3.88 d (1H, 10-H, J = 7.3, J = 4.3 Hz), 4.00 d (1H,
2
3
10-H, J = 7.3 Hz), 4.69 d (1H, 1-H, J1,10 = 4.3 Hz),
3
3
4
4.78 d (1H, 3-H, J3,2 = 10.1 Hz), 5.21 s (1H, 8-H),
2-H, J2,3 = 10.1, J2,5 = 2.6 Hz), 3.85 d.d (1H, 10-H,
6.55 d (1H, 5-H, J5,2 = 2.7 Hz). 13C NMR spectrum,
4
3
2
2J = 7.2, J = 4.3 Hz), 3.99 d (1H, 10-H, J = 7.2 Hz),
3
3
δC, ppm: 14.09 (Me), 22.62 (CH2), 24.09 (Me), 24.65
(CH2), 29.17 (CH2), 29.71 (CH2), 30.18 (CH2), 31.77
(CH2), 33.58 (CH2), 47.44 (C2), 51.79 (C4), 70.85
(C10), 73.62 (C1), 97.37 (C3), 99.52 (C8), 131.31 (C6),
147.60 (C5), 188.28 (C=O). Mass spectrum, m/z: 338
[M + H]+, 336 [M – H]–. Found, %: C 63.10; H 7.85;
N 4.30. C18H27NO5. Calculated, %: C 64.02; H 8.00;
N 4.15.
4.70 d (1H, 1-H, J1,10 = 4.3 Hz), 5.0 d (1H, 3-H, J =
10.1 Hz), 5.20 s (1H, 8-H), 6.61 d (1H, 5-H, J5,2
4
=
2.6 Hz). 13C NMR spectrum, δC, ppm: 24.79 (CH2),
25.31 (CH2), 31.83 (CH2), 36.68 (CH2), 48.15 (C2),
58.55 (C4), 70.80 (C10), 73.47 (C1), 95.25 (C3), 99.53
(C8), 130.33 (C6), 147.85 (C5), 188.35 (C=O). Mass
spectrum, m/z: 266 [M + H]+, 264 [M – H]–. Found, %:
C 60.50; H 6.30; N 5.30. C14H17NO5. Calculated, %:
C 60.15; H 6.08; N 5.01.
(1S,2R,3S,4RS,8R)-4-Methyl-4-isobutyl-3-nitro-
9,11-dioxatricyclo[6.2.1.02,6]undec-5-en-7-one
(IIIa/IIIb). Yield 66%, colorless oily substance, Rf 0.5
(petroleum ether–ethyl acetate, 3:1).
(1′S,2′R,3′S,8′R)-3′-Nitrospiro[cyclohexane-1,4′-
[9,11]dioxatricyclo[6.2.1.02,6]undec]-5′-en-7′-one
(V). Yield 96%, colorless crystals, mp 50–53°C, Rf 0.5
(petroleum ether–ethyl acetate, 3:1), [α]D20 = –98.2°
1
(4R)-Epimer IIIa. H NMR spectrum, δ, ppm:
3
1
0.87 d and 0.94 d (3H each, Me2CH, J = 6.6 Hz),
(c = 0.5, CHCl3). H NMR spectrum, δ, ppm: 1.20 m
2
3
1.25 d.d (1H, 4-CH2, J = 13.6, J = 4.9 Hz), 1.47 d.d
(2H, 3′-H), 1.65 m (7H, 1′-H, 2′-H, 4′-H, 5′-H), 2.07 m
(1H, 4-CH-2, 2J = 13.6, 3J = 7.3 Hz), 1.52 s (3H, 1″-H),
(1H, 1′-H), 3.78 d.d (1H, 2-H, J2,3 = 10.1, J2,5
=
3
4
3
2
3
1.70 m (1H, CHMe2), 3.70 d.d (1H, 2-H, J2,3 = 10.3,
2.7 Hz), 3.85 d.d (1H, 10-H, J = 7.2, J = 4.4 Hz),
4.0 d (1H, 10-H, J = 7.2 Hz), 4.68 d (1H, 1-H, J1,10 =
4.4 Hz), 4.69 d (1H, 3-H, J = 10.1 Hz), 5.22 s (1H,
8-H), 6.98 d (1H, 5-H, J5,2 = 2.7 Hz). C NMR spec-
trum, δC, ppm: 20.80 (C3′), 23.44 (C2′), 25.39 (C4′),
30.12 (C5′), 31.34 (C1′), 46.96 (C2), 52.89 (C4), 70.83
(C10), 73.50 (C1), 97.61 (C3), 99.53 (C8), 131.73 (C6),
4J2, 5 = 2.7 Hz), 3.87 d.d (1H, 10-H, J = 7.3, J =
2
3
2
3
2
3
4.4 Hz), 4.10 d (1H, 10-H, J = 3.0 Hz), 4.69 d (1H,
1-H, 3J1,10 = 4.4 Hz), 4.75 d (1H, 3-H, 3J3,2 = 10.3 Hz),
4
13
4
5.21 s (1H, 8-H), 6.66 d (1H, 5-H, J5, 2 = 2.7 Hz).
13C NMR spectrum, δC, ppm: 24.34 (Me), 24.42 (Me),
24.77 (Me), 24.82 (CMe2), 41.87 (4-CH2), 47.03 (C2),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

REACTION OF α-BROMOLEVOGLUCOSENONE
459
145.30 (C5), 188.47 (C=O). Mass spectrum, m/z: 338
[M + H]+, 336 [M – H]–. Found, %: C 61.05; H 5.91;
N 4.31. C15H19NO5. Calculated, %: C 61.37; H 6.48;
N 4.77.
[M – H]–. Found, %: C 66.17; H 8.51; N 3.50.
C21H31NO5. Calculated, %: C 66.76; H 8.21; N 3.71.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 11-03-97 024-r_povolzh’e_a) and by the Federal
Special-Purpose Program “Scientific and Scientific–
Pedagogical Staff of Innovation Russia (state contract
no. 14.740.11.0367).
(1′S,2′R,3′S,8′R)-3-Nitrospiro[cyclododecane-
1,4′-[9,11]dioxatricyclo[6.2.1.02,6]undec]-5′-en-7′-
one (VI). Yield 64%, colorless crystals, mp 122–
125°C, Rf 0.57 (petroleum ether–ethyl acetate, 3:1),
[α]D20 = –120° (c = 0.25, CHCl3). 1H NMR spectrum, δ,
REFERENCES
ppm: 1.45 m (16H, CH2), 1.51 m (4H, CH2), 1.70 m
3
and 1.89 m (1H each, 1′-H), 3.80 d.d (1H, 2-H, J2,3
=
1. Valeev, F.A., Gorobets, E.V., and Miftakhov, M.S., Izv.
Ross. Akad. Nauk, Ser. Khim., 1997, p. 1241.
2. Tsypysheva, I.P., Valeev, F.A., Kalimullina, L.Kh., Spiri-
khin, L.V., and Safarov, M.G., Russ. J. Org. Chem., 2003,
vol. 39, p. 1055.
3. Faizullina, L.Kh., Safarov, M.G., Spirikhin, L.V., Kolos-
nitsyn, V.S., Kondrova, Yu.S., and Valeev, F.A., Russ. J.
Org. Chem., 2011, vol. 47, p. 914.
4
2
3
10.1, J2,5 = 2.7 Hz), 4.83 d (1H, 10-H, J = 7.3, J =
4.3 Hz), 3.95 d (1H, 10-H, J = 7.3 Hz), 4.67 d (1H,
1-H, J1,10 = 4.3 Hz), 4.91 d (1H, 3-H, J = 10.1 Hz),
2
3
3
4
5.20 s (1H, 8-H), 6.52 d (1H, 5-H, J5,2 = 2.7 Hz).
13C NMR spectrum, δC, ppm: 19.12, 19.28, 22.13,
22.23, 22.59, 22.66, 25.88, 26.43, 26.61, 26.88 (CH2);
34.53 (C1′), 49.10 (C2), 55.17 (C4), 70.81 (C10), 73.39
(C1), 97.14 (C3), 99.46 (C8), 130.54 (C6), 147.54 (C5),
188.25 (C=O). Mass spectrum, m/z: 364 [M + H]+, 362
4. Fraser, H.B. and Kon, G.A.R., J. Chem. Soc., 1934,
p. 604.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012