Infl uence of steric factors on the direction of reactions

Full text of DOI:10.1134/S1070428011080252

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 8, pp. 1256−1258. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © N.K. Selezneva, F.A. Gimalova, R.F. Valeev, N.Z. Yagafarov, M.S. Miftakhov, 2011, published in Zhurnal Organicheskoi Khimii, 2011,
Vol. 47, No. 8, pp. 1236−1238.
SHORT
COMMUNICATIONS
Influence of Steric Factors on the Direction of Reactions
N. K. Selezneva, F. A. Gimalova, R. F. Valeev, N. Z. Yagafarov,
and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences
Ufa, 450054 Russia; e-mail: bioreg@anrb.ru
Received January 15 2011
DOI: 10.1134/S1070428011080252
Sterical loading, topology, and the character of the or-
ganic molecule functionalization sometimes lead to the
“uncommon” course of typical reactions with its partici-
pation. One of such compounds is epoxycyclohexanone
I that we have recently described [1].
VIII. Usually the reduction with LiAlH4 of trisubstituted
epoxides provides a tertiary alcohol. The assignment of
stereoisomeric diols VII and VIII was done based on
the characteristic doublets of H3 in the 1H NMR spectra.
Whereas for 2,3-trans-isomer VII J3,2 is 11.2 Hz [δ(H3)
3.30 ppm], in the isomer VIII J3,2 is 5.2 Hz [δ(H3)
3.51 ppm] (analogous examples have been described in
[4]). For further identification diol VIII was converted
into diacetate IX.
O
O
O
O
OH
O3
II
m-ClC6H4CO3H
OH
HO
OH
HO
O
O
LiAlH4
+
IV
THF, Δ
I
NaBH4
O
VI, 33%
VII, 27%
OAc
III
O
HO
OH
HO
HO
OH
AcO
HIO4
THF_H2O
Ac2O_Py
+
IV
V
IX
VIII, 7%
Our attempts to convert it into hydroxycyclohexa-
none II by ozonolysis under the conditions of Criegee
rearrangement [2, 3] resulted only in diketone III [1]
inert with respect to m-chloroperbenzoic acid. We also
failed to perform the oxidative cleavage of epoxyalcohol
IV by treating with HIO4, we obtained only diol V.At the
reduction of epoxyalcohol IV with LiAlH4 alongside the
expected diol VI we isolated regioisomeric diols VII and
Thus except for the reduction of the epoxyketone I
with sodium borohydride into alcohol IV the other reac-
tions of these compounds proceeded by unexpected routes
or with the partial formation of abnormal products.
(1R,3R,5S)-4,4-Dimethyl-5-isopropenyl-2-methy-
lidenecyclohexane-1,3-diol (V). To a solution of 0.08
g (0.41 mmol) of compound IV in 5 ml of the mixture
1256

INFLUENCE OF STERIC FACTORS ON THE DIRECTION OF REACTIONS
1257
(1R,2R,3S,5S)-5-Isopropenyl-2,4,4-trimethyl-
cyclohexane-1,3-diol (VII). Colorless crystals, Rf 0.2
(petroleum ether–ethyl acetate, 2:1), mp 122–123°C,
[α]D20 –29.1° (C 1.4, CHCl3). 1H NMR spectrum (CDCl3),
δ, ppm: 0.83 s and 0.98 s (6H, gem-CH3), 1.09 d (3H,
CH3, J 7.0 Hz), 1.23 br.s (1H, OH), 1.54 t (J 3.3 Hz),
1.59 t (1H, CH2, J 3.3 Hz), 1.73 br.s (1H, OH), 1.75 s
(3H, CH3), 1.80–1.90 m (2H, CH), 2.33 d.d (1H, CH2,
J 13.5, 3.3 Hz), 3.30 d (1H, H3, J 11.2 Hz), 3.91 q (1H,
H1, J 2.7 Hz), 4.68 s (1H, =CH2), 4.90 s (1H, =CH2).
13C NMR spectrum (CDCl3), δ, ppm: 13.38 (CH3), 14.97
and 24.19 (gem-CH3), 26.47 (CH3), 34.97 (CH2), 39.63
(C4), 38.06 (C5), 45.96 (C2), 71.21 (C1), 78.26 (C3),
113.55 (=CH2), 146.14 (C1’). Mass spectrum, m/z (Irel,
%): 198 [M]+ (2), 180 [M – H2O]+ (12), 165 [M – H2O –
CH3]+ (14), 147 (16), 137 (20), 129 (39), 122 (40), 109
(45), 107 (75), 96 (76), 81 (89), 71 (100), 69 (58), 59
(66), 55 (68), 53 (25).
THF–water, 3 : 1, was added 0.24 g (1.25 mmol) of
HIO4, and the mixture was stirred for 8 h. Then THF
was distilled off, the residue was treated with CHCl3, the
combined organic solutions were washed with brine, dried
with MgSO4, and evaporated under a reduced pressure.
The residue was subjected to column chromatography on
SiO2 (eluent petroleum ether–ethyl acetate, 2 : 1). Yield
0.03 g (~40%), [α]D20 –10.0° (C 0.60, CHCl3). 1H NMR
spectrum (CDCl3), δ, ppm: 0.70 s and 1.08 s (6H, gem-
CH3), 1.61 br.s (2H, OH), 1.68 t (J 2.8, 3.6 Hz), 1.73 t
(1H, CH2, J 2.8, 3.4 Hz), 1.78 s (3H, CH3), 1.87 d.t (1H,
H5, J 13.7, 3.4 Hz), 2.55 d.d (1H, CH2, J 13.3, 3.6 Hz),
4.27 s (1H, H3), 4.49 t (1H, H1, J 2.8 Hz), 4.71 s (1H,
=CH2), 4.94 s (1H, =CH2), 5.07 d (2H, =CH2, J 2.0 Hz).
13C NMR spectrum (CDCl3), δ, ppm: 12.68 (CH3), 24.42
and 25.83 (gem-CH3), 35.19 (CH2), 41.45 (C4), 46.37
(C5), 72.99 (C1), 76.15 (C3), 109.06 (=CH2), 113.70
(=CH2), 145.65 (C1’), 149.96 (C2).
(1R,2S,3S,5S)-5-Isopropenyl-2,4,4-trimethyl-
cyclohexane-1,3-diol (VIII). Colorless crystals, Rf 0.15
(petroleum ether–ethyl acetate, 2:1), mp 160–162°C,
Reduction of epoxide IV with LiAlH4 in THF.
To a solution of 0.3 g (1.53 mmol) of compound IV in
10 ml of anhydrous THF was added at stirring 0.23 g
(6.05 mmol) of LiAlH4, the mixture was boiled for 6 h.
On cooling the reaction mixture to room temperature 5 ml
of saturated NH4Cl solution was added, THF was distilled
off, the residue was treated with CHCl3, the combined
organic solutions were washed with 5% solution of HCl,
next with brine, dried with MgSO4, and evaporated. The
residue was subjected to column chromatography on SiO2
(eluent petroleum ether–ethyl acetate, 2 : 1). We obtained
0.1 g (33%) of compound VI, 0.08 g (27%) of diol VII,
and 0.02 g (7%) of diol VIII.
1
[α]D20 +21.0° (C 0.935, MeOH). H NMR spectrum
[(CD3)2CO], δ, ppm: 0.87 s and 0.98 s (6H, gem-CH3),
0.97 d (3H, CH3, J 7.2 Hz), 1.41 d.t (1H, CH2, J 3.6
and 11.0 Hz), 1.76 s (3H, CH3), 1.95–2.00 m (2H, CH),
2.45 d.d (1H, CH2, J 11.9 and 3.6 Hz), 3.51 d (1H, H3,
J 5.2 Hz), 3.54 br.s (1H, OH), 3.66 t (1H, H1, J 4.9 Hz),
3.84 br.s (1H, OH), 4.70 d.d (1H, =CH2, J 0.7 and 1.8 Hz),
4.83 d.d (1H, =CH2, J 1.3 and 2.5 Hz). 13C NMR spec-
trum (CDCl3), δ, ppm: 12.75 (CH3), 17.41 and 22.90
(gem-CH3), 28.21 (CH3), 31.08 (CH2), 39.39 (C4), 41.81
(C5), 46.79 (C2), 70.81 (C1), 74.61 (C3), 112.53 (=CH2),
147.10 (C1’).
(1R,2R,4S)-4-Isopropenyl-1,3,3-trimethylcyclohex-
ane-1,2-diol (VI). Colorless crystals, Rf 0.3 (petroleum
ether–ethyl acetate, 2 : 1), mp 77–77.5°C, [α]D20 –10.3°
(1R,2S,3S,5S)-5-Isopropenyl-2,4,4-trimethyl-
cyclohexane-1,3-diyl diacetate (IX). Colorless oily sub-
stance, [α]D20 –20.0° (C 0.24, CHCl3). 1H NMR spectrum
(CDCl3), δ, ppm: 0.91 s and 0.97 s (6H, gem-CH3), 0.99 d
(3H, CH3, J 7.5 Hz), 1.57–1.64 m (2H, CH, CH2), 1.79 s
(3H, CH3), 1.97 d (J 3.3 Hz), 2.02 t (1H, CH, J 3.3 Hz),
2.08 s and 2.09 s (3H each, COCH3), 2.34 d.d (1H, CH2,
J 11.4 and 3.6 Hz), 4.73 br.s (1H, =CH2), 4.89–4.93 m
(1H, H3), 4.91 C (1H, =CH2), 4.96 t (1H, H1, J 3.8 Hz).
13C NMR spectrum (CDCl3), δ, ppm: 13.41 (CH3), 19.0
and 23.37 (gem-CH3), 20.96 and 21.39 (COCH3), 28.14
(CH3), 28.38 (CH2), 35.31 (C5), 38.43 (C4), 47.39 (C2),
74.04 (C1), 78.14 (C3), 114.45 (=CH2), 145.24 (C1’),
170.44 and 170.56 (COCH3).
1
(C 1.64, CHCl3). H NMR spectrum (CDCl3), δ, ppm:
0.97 s (3H, gem-CH3), 1.03 s (3H, gem-CH3), 1.42 s (3H,
CH3), 1.45–1.70 m (4H, 2CH2), 1.73 s (3H, CH3), 2.26 d.d
(1H, H4, J 6.8, 2.0 Hz), 2.65 br.s (1H, OH), 2.93 br.s (1H,
OH), 3.10 s (1H, H2), 4.65 br.s (1H, =CH2), 4.87 br.s
(1H, =CH2). 13C NMR spectrum (CDCl3), δ, ppm: 23.02
and 24.28 (gem-CH3), 25.45 (CH2), 26.62 (CH3), 28.19
(CH3), 35.29 (CH2), 38.54 (C3), 46.99 (C4), 72.33 (C1),
83.26 (C2), 113.10 (=CH2), 146.70 (C1’). Mass spectrum,
m/z (Irel, %): 198 [M]+ (1), 180 [M – H2O]+ (8), 168 [M –
2CH3]+ (9), 165 [M – H2O – CH3]+ (14%), 151 (10), 137
(20), 125 (20), 111 (30), 109 (82), 108 (49), 97 (78), 95
(78), (89), 72 (85), 71 (100), 69 (67), 68 (58), 58 (50),
55 (48), 53 (25).
IR spectra were recorded on a spectrophotometer IR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

SELEZNEVA et al.
1258
Prestige-21 Shimadzu from thin films. 1H and 13C NMR
spectra were registered on a spectrometer Bruker AM-
300 at operating frequencies 300.13 and 75.47 MHz
respectively, internal reference TMS. The optical rota-
tion was measured on a polarimeter Perkin Elmer-341.
Mass spectra were obtained on an instrument Thermo
Finnigan MAT 95XP, ionizing electrons energy 70 eV,
ionizing chamber temperature 200°C, temperature of
sample admission 50–270°C, heating rate 22 deg/min.
The reaction progress was monitored by TLC on Sorbfil
plates (Russia), spots visualized by solution of anisalde-
hyde in ethanol acidified with sulfuric acid followed by
heating to 120–150°C. In the column chromatography
freshly distilled eluents were used: ethyl acetate and light
petroleum ether (bp 40–70°).
ACKNOWLEDGMENTS
The study was performed under a financial support
of the Ministry of Education and Science (State contract
no. 4.740.11.0367).
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011