Annulation of unsaturated silyl nitronates

Article abstract of DOI:10.1007/s11172-014-0494-x

The intramolecular dipolar [3+2]-cycloaddition of acyclic δ,ε- and ε,ζ-unsaturated silyl nitronates was used in the stereoselective synthesis of functionalized cyclopentanone and cyclohexanone, respectively. The reaction with the γ,δ-unsaturated analog di

Full text of DOI:10.1007/s11172-014-0494-x

Russian Chemical Bulletin, International Edition, Vol. 63, No. 3, pp. 696—700, March, 2014
696
Annulation of unsaturated silyl nitronates
A. V. Lozanova, M. V. Zlokazov, and V. V. Veselovsky
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: ves@ioc.ac.ru
The intramolecular dipolar [3+2]ꢀcycloaddition of acyclic ,ꢀ and ,ꢀunsaturated silyl
nitronates was used in the stereoselective synthesis of functionalized cyclopentanone and cycloꢀ
hexanone, respectively. The reaction with the ,ꢀunsaturated analog did not afford the correꢀ
sponding cyclobutanone.
Key words: unsaturated silyl nitronates, intramolecular dipolar [3+2]ꢀcycloaddition, stereoꢀ
selective synthesis, cyclopentaisoxazolidines, cyclohexaisoxazolidines, hydroxyiminocycloꢀ
alkanes, deoximination, cyclopentanones, cyclohexanones.
Scheme 2
The intramolecular dipolar [3+2]ꢀcycloaddition of unꢀ
saturated silyl nitronates is an efficient route for the stereoꢀ
selective construction of carboꢀ and heterocycles.1 Earꢀ
lier,2 we have used this reaction in the total synthesis of
a number of natural compounds. In the present work, we
studied this reaction for nitroalkenes 1a—c containing
hydrocarbon chains of different length. The aim of this
study is to access derivatives of fourꢀ, fiveꢀ, and sixꢀmemꢀ
bered carbocycles promising as synthons in the synthesis
of natural compounds containing such moieties.
The previously unknown compounds 1a,c and nitroꢀ
olefin 1b described earlier3 were prepared by the nitroꢀ
aldol condensation (the Henry reaction) of the correspondꢀ
ing aldehydes 2 with nitromethane giving nitro alcohols 3
(Scheme 1).
Scheme 1
4: n = 1 (a), 2 (b), 3 (c)
Reagents and conditions: HN(TMS)2, Et3N (HMPA), .
i. MeNO2/ButOK, THF/ButOH, 20 C; ii. TBSCl/C3H4N2,
DMF, 20 C
that the longꢀterm storage of nitropentene derivative 1a
under these conditions led to the gradual resinification of
the reaction mixture, while the expected cyclobutaisoxꢀ
azolidine 5 was not obtained. Attempts to perform this
reaction with TMSCl or N,Oꢀbis(trimethylsilyl)acetamide
as silylating agents failed. An attempt to use HMPA as the
n = 1 (a), 2 (b), 3 (c)
Then nitroolefins 1a—c were subjected to silylation
with hexamethyldisilazane (HMDS) in the presence of
Et3N at 110 C (cf. lit. data2,3) (Scheme 2). It was found
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 0696—0700, March, 2014.
1066ꢀ5285/14/6303ꢀ0696 © 2014 Springer Science+Business Media, Inc.

Annulation of olefinic silyl nitronates
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 3, March, 2014
697
catalyst for this reaction (cf. lit. data4) was also unsuccessꢀ
ful. The failure is apparently attributed to steric hindrance
to the formation of the fourꢀmembered carbocycle in interꢀ
mediate 4 at n = 1. Meanwhile, nitrohexene derivative 1b
(n = 2) and nitroheptene derivative 1c (n = 3) undergo the
required cyclization. Cyclopentaꢀ and cyclohexaisoxazolꢀ
idines 6 and 7 were synthesized with high stereoselectivity
(cf. lit. data1—3).
The deoximination of oximes 8 and 9 was carried
out in the absence of a solvent by the trituration with
HIO4•2H2O in a mortar for a short period of time folꢀ
lowed by the extraction of the reaction products (cf. lit.
data6) to give the corresponding cycloalkanones 10 and 11
in good yields (Scheme 4).
Scheme 4
The structures of the previously unknown compounds
1a,c, 6, and 7 were confirmed by elemental analysis and
spectroscopy, as well as by the transformation of comꢀ
pounds 6 and 7 into mixtures of synꢀ and antiꢀoximes 8
and 9* (Scheme 3). It should be noted that we isolated, in
addition to silyl derivatives 8a,b, more than 30% of their
desilylation products 8c,d, from the reaction mixture obꢀ
tained by the cleavage of isoxazolidine 6 with NH4F in
MeOH. The desilylation did not occur in the reaction
with the use of NaOMe. The configuration of the C=N
double bond in both pairs of isomers of 8 and 9 was estabꢀ
lished based on 13C NMR spectroscopic data, because it is
known5 that the oxime hydroxy group exerts a substantial
shielding effect on the adjacent ꢀcarbon atom. For exꢀ
ample, the signals of the C(2) atoms in anti isomer 8a and
syn isomer 8b are at  73.9 and 69.0, respectively ( 73.4
for 8c and 70.7 for 8d).
Reagents and conditions: HIO4•2 H2O, 20 C.
To conclude, we studied the intramolecular dipolar
[3+2]ꢀcycloaddition of unsaturated silyl nitronates, in
which the double bond is differently spaced from the nitrꢀ
onate group. This reaction can be used for the stereoselecꢀ
tive synthesis of functionalized cyclopentanones and cycloꢀ
hexanones.
Scheme 3
Experimental
The melting points were measured on a Kofler hotꢀstage
apparatus. The IR spectra were recorded on a Bruker ALPHA´T
instrument. The 1H and 13C NMR spectra of solutions in CDCl3
(unless otherwise stated) were measured at 298 K with respect to
the signals of the solvent ( 7.27 for H and  77.0 for C, respecꢀ
tively) on Bruker ACꢀ200 (200.13 MHz) and Bruker AMꢀ300
(75.47 MHz) spectrometers. Highꢀresolution mass spectra (ESI)
were obtained on a Bruker micrOTOF II spectrometer by applyꢀ
ing a 4.5 kV potential at the capillary with a direct syringe injecꢀ
tion of a solution of the sample in methanol (3 L min–1) in
positive ion mode (the mass range was 500—3000 Da), the main
nitrogen flow was 4 L min–1 (180 C). The target products were
isolated by column chromatography on silica gel 60 (0.04—0.06 mm,
Fluka). The values of Rf were measured on Silufol plates with
a fixed layer. The solvents, including petroleum ether with b.p.
40—70 C, were purified and dried according to standard
procedures. The commercially available reagents MeNO2, ButOK,
Et3N, HMDS, imidazole, ButMe2SiCl, and HIO4•2 H2O (Acros
Organics) were used. Butꢀ3ꢀenal (2a),7 pentꢀ4ꢀenal (2b),8 and
hexꢀ5ꢀenal (2c)9 were prepared according to known procedures.
( )ꢀ1ꢀNitropentꢀ4ꢀenꢀ2ꢀol (3a). tertꢀButanol (15 mL) and
MeNO2 (6.76 g, 110.78 mmol) were added to a stirred solution
of aldehyde 2a (~3.7 g, ~52.8 mmol) in CH2Cl2 (15 mL), which
was prepared according to a known procedure7 from octaꢀ1,7ꢀ
Reagents and conditions: i. KF, MeOH, –60  20 C; ii. MeONa,
PhH, 20 C.
* synꢀ and antiꢀOximes 8 and 9 readily undergo interconversion
and exist in solution in a dynamic equilibrium (1H NMR and
TLC data).

698
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Lozanova et al.
dieneꢀ4,5ꢀdiol (5.2 g, 36.57 mmol), under argon at 20 C. Then
ButOK (0.6 g, 5.35 mmol) was added portionwise. The reaction
mixture was stirred for 2 h and then diluted with MeOBut
(30 mL), washed with water and a saturated NaCl solution, dried
with Na2SO4, and concentrated in vacuo. The residue was chroꢀ
matographed on a column with silica gel. The elution with a 1 : 1
petroleum ether—MeOBut mixture gave nitro alcohol 3a in
a yield of 3.35 g (~35%) as a colorless liquid, b.p. 73—75 C
(1 Torr). Found (%): C, 45.96; H, 6.83; N, 10.64. C5H9NO3.
Calculated (%): C, 45.80; H, 6.92; N, 10.68. IR (thin layer),
/cm–1: 646, 739, 926, 997, 1086, 1072, 1200, 1385, 1423, 1555,
1643, 2928—3082, 3426. 1H NMR (200.13 MHz), : 2.33 (m, 2 H,
H2C(3)); 2.77 (br.s, 1 H, HO); 4.33—4.51 (m, 3 H, CHO,
CH2NO2); 5.19 (d, 1 H, HaC(5), J = 16.3 Hz); 5.21 (d, 1 H,
HbC(5), J = 10.0 Hz); 5.70—5.92 (dddd, 1 H, HC=, J = 7.1 Hz,
J = 7.1 Hz, J = 10.0 Hz, 16.3 Hz). 13C NMR (50.03 MHz),
: 38.4 (C(3)); 67.9 (C(4)); 80.0 (C(5)); 119.7 (C(1)); 132.2 (C(2)).
( )ꢀ4ꢀtertꢀButyl(dimethyl)silyloxyꢀ5ꢀnitropentꢀ1ꢀene (1a).
Imidazole (1.17 g, 17.19 mmol) was added to a stirred solution of
nitro alcohol 3a (1.0 g, 7.63 mmol) and TBSCl (1.23 g, 8.16 mmol)
in DMF (6 mL) under argon at 20 C. The reaction mixture was
stirred at 20 C for 12 h and then diluted with water and extractꢀ
ed with a 9 : 1 petroleum ether—MeOBut mixture. The extract
was washed with water and a saturated NaCl solution, dried with
Na2SO4, and concentrated in vacuo. The residue was chromatoꢀ
graphed on a column with silica gel. The gradient elution from
petroleum ether to its mixture with MeOBut (7%, v/v) gave silyl
ether 1a in a yield of 1.56 g (83%) as a colorless oil, Rf 0.5
(petroleum ether—MeOBut, 95 : 5). IR (thin layer), /cm–1: 668,
779, 839, 922, 994, 1003, 1110, 1258, 1387, 1465, 1557, 1643,
2859—2957. Highꢀresolution MS (ESI), found: m/z 268.1334;
ed with a 9 : 1 petroleum ether—MeOBut mixture. The extract
was washed with water and a saturated NaCl solution, dried with
Na2SO4, and concentrated in vacuo. The residue was chromatoꢀ
graphed on a column with silica gel. The gradient elution from
petroleum ether to its mixture with MeOBut (5%, v/v) gave silyl
ether 1a in a yield of 0.81 g (85%) as a colorless oil, Rf 0.6
(petroleum ether—MeOBut, 95 : 5). IR (thin layer), /cm–1: 771,
811, 838, 914, 941, 996, 1111, 1257, 1387, 1463, 1557, 1642,
2859, 2931, 2953, 3079. Highꢀresolution MS (ESI), found: m/z
274.1841 and 298.1656; C13H27NO3Si; calculated: m/z 274.1833
[M + H]+ and 298.1652 [M + Na]+. 1H NMR (200.13 MHz), :
0.04 (s, 3 H, MeSi); 0.09 (s, 3 H, Me´Si); 0.87 (s, 9 H, Me3CSi);
1.37—1.67 (m, 4 H, H2C(4), H2C(5)); 2.08 (m, 2 H, H2C(3));
2.27—4.48 (m, 3 H, H2CN, HCO); 4.93—5.12 (m, 2 H, H2C(1));
5.78 (dddd, 1 H, HC(2), J = 6.6 Hz, J = 6.6 Hz, J = 10.1 Hz,
J = 16.7 Hz).
(3aS*,6S*,6aS*)ꢀ6ꢀtertꢀButyl(dimethyl)silyloxyꢀ1ꢀ(trimethꢀ
ylsilyloxy)perhydrocyclopenta[c]isoxazole (6). A mixture of comꢀ
pound 1b (1.55 g, 6 mmol), HMDS (7 mL), and Et3N (0.62 g,
6.1 mmol) was heated under argon at 115 C for 10 h and then
concentrated in vacuo. The residue was distilled off. Compound 6
was obtained in a yield of 1.57 g (80%) as a colorless oil with b.p.
72—75 C (0.08 Torr). IR (thin layer), /cm–1: 776, 842, 881,
925, 975, 1046, 1068, 1114, 1136, 1251, 1362, 1472, 1559,
2858—2958. Highꢀresolution MS (ESI), found: m/z 332.2069
and 354.1888; C15H33NO3Si2; calculated: m/z: 332.2072 [M + H]+
1
and m/z 354.1891 [M + Na]+. H NMR (200.13 MHz), : 0.07
(s, 3 H, MeSi); 0.10 (s, 3 H, Me´Si); 0.89 (s, 9 H, Me3CSi);
1.37—1.67 (m, 4 H, H2C(4), H2C(5)); 3.1 (m, 1 H, HC(3a));
3.61 (d, 1 H, HC(3), J = 7.2 Hz); 3.74 (dd, 1 H, H´C(3), J = 7.2 Hz,
J = 3.6 Hz); 4.02 (br.dd, 1 H, HC(6a), J = 8.9 Hz, J = 6.1 Hz);
4.30 (br.t, 1 H, HC(6), J = 7.7 Hz).
1
C11H23NO3Si; calculated: m/z 268.1339 [M + Na]+. H NMR
(200.13 MHz), : 0.03 (s, 3 H, MeaSi); 0.09 (s, 3 H, MebSi); 0.86
(s, 9 H, Me3CSi); 2.34 (br.t, 2 H, H2C(3), J = 6.3 Hz); 4.35
(br.d, 1 H, CHaNO2, J = 7.1 Hz); 4.37 (br.d, 1 H, CHbNO2,
J = 4.7 Hz); 4.47 (m, 1 H, CHO); 5.14 (br.d, 1 H, HaC(1),
J = 16.9 Hz); 5.16 (br.d, 1 H, HbC(1), J = 10.1 Hz); 5.80 (dddd, 1 H,
HC=, J = 6.3 Hz, J = 6.3 Hz, J = 10.1 Hz, J = 16.9 Hz).
( )ꢀ1ꢀNitroheptꢀ6ꢀenꢀ2ꢀol (3c). Potassium tertꢀbutoxide
(0.14 g, 1.2 mmol) was added portionwise to a stirred solution of
aldehyde 2c (1.27 g, 13 mmol) and MeNO2 (1.57 g, 25.7 mmol)
in a 1 : 1 ButOH—THF mixture (7 mL) under argon at 20 C.
The reaction mixture was stirred for 1.5 h and then diluted with
MeOBut (20 mL), washed with water and a saturated NaCl soluꢀ
tion, dried with Na2SO4, and concentrated in vacuo. The residue
was chromatographed on a column with silica gel. The gradient
elution from petroleum ether to its mixture with MeOBut (30%,
v/v) gave nitro alcohol 3c in a yield of 1.26 g (61%) as a colorless
oil with b.p. 68—70 C (0.09 Torr). Found (%): C, 52.83; H, 8.30;
N, 9.01. C7H13NO3. Calculated (%): C, 52.82; H, 8.23; N 8.80.
IR (thin layer), /cm–1: 915, 999, 997, 1096, 1203, 1384, 1420,
1555, 1641, 2864, 2938, 2977, 3078, 3418. 1H NMR (200.13 MHz),
: 1.38—1.76 (m, 4 H, H2C(3), H2C(4)); 2.12 (m, 2 H, H2C(5));
2.45 (br.s, 1 H, OH); 4.23—4.55 (m, 3 H, CHO, CH2N);
4.93—5.14 (m, 2 H, H2C=); 5.80 (ddt, 1 H, —HC=, J = 16.9 Hz,
J = 10.1 Hz, J = 6.6 Hz).
(3aS*,7S*,7aS*)ꢀ7ꢀtertꢀButyl(dimethyl)silyloxyꢀ1ꢀ(trimethꢀ
ylsilyloxy)octahydroꢀ2,1ꢀbenzisoxazole (7). A mixture of comꢀ
pound 1c (1.04 g, 3.8 mmol), HMDS (4.3 mL), and Et3N (0.39 g,
3.8 mmol) was heated under argon at 110—125 C for 20 h and
then concentrated in vacuo. The residue was distilled off. Comꢀ
pound 7 was obtained in a yield of 1.2 g (92%) as a colorless oil
with b.p. 92—95 C (0.08 Torr). IR (thin layer), /cm–1: 673,
777, 814, 884, 910, 923, 1038, 1091, 1133, 1251, 1361, 1462,
2859—2956. Highꢀresolution MS (ESI), found: m/z 346.2235
and 368.2043; C16H35NO3Si2; calculated: m/z 346.2228 [M + H]+
and 368.2048 [M + Na]+. 1H NMR (200.13 MHz), : 0.11 (s, 3 H,
MeaSi); 0.17 (s, 3 H, MebSi); 0.91 (s, 9 H, Me3CSi); 1.18—2.13
(m, 6 H, H2C(4), H2C(5), H2C(6)); 2.76 (m, 1 H, HC(3a)); 3.84
(dd, 1 H, HaC(3), J = 8.7 Hz, J = 8.1 Hz); 3.92 (dd, 1 H,
HbC(3), J= 8.1 Hz, J = 7.6 Hz); 4.30 (dd, 1 H, HC(7a), J = 10.3 Hz,
J = 8.1 Hz); 4.43 (dd, 1 H, HC(7), J = 10.6 Hz, J = 8.1 Hz).
antiꢀ(2S*,5S*)ꢀ2ꢀtertꢀButyl(dimethyl)silyloxyꢀ (8a), synꢀ
(2S*,5S*)ꢀ2ꢀ(tertꢀbutyldimethylsilyloxy)ꢀ (8b), antiꢀ(2S*,5S*)ꢀ
2ꢀhydroxyꢀ (8c), and synꢀ(2S*,5S*)ꢀ2ꢀhydroxyꢀ5ꢀhydroxymethꢀ
ylꢀ1ꢀhydroxyiminocyclopentane (8d). Method A. A solution of
isoxazolidine 6 (1.45 g, 4.38 mmol) in THF (13 mL) was added
to a vigorously stirred suspension of NH4F (235 mg, 6.34 mmol)
in MeOH (12 mL) under argon at –60 C. The reaction mixture
was warmed to 20 C, allowed to stand for 1 h, and concentrated
in vacuo. The residue was treated with EtOAc and water. The
organic layer was separated, washed with water and a saturated
NaCl solution, dried with Na2SO4, and concentrated in vacuo.
The residue was chromatographed on a column with silica gel.
The elution with a 1 : 4 petroleum ether—MeOBut mixture gave
( )ꢀ6ꢀtertꢀButyl(dimethyl)silyloxyꢀ7ꢀnitroheptꢀ1ꢀene (1c).
Imidazole (0.6 g, 8.8 mmol) was added to a stirred solution of
nitro alcohol 3c (0.56 g, 3.5 mmol) and TBSCl (0.63 g, 4.2 mmol)
in DMF (3 mL) under argon at 20 C. The reaction mixture was
stirred at 20 C for 12 h and then diluted with water and extractꢀ

Annulation of olefinic silyl nitronates
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 3, March, 2014
699
a mixture of oximes 8a/b in a ratio of ~4/1* in a yield of 0.57 g
(50%). H NMR (200.13 MHz), : 0.09 (s, 6 H, Me2Si) (8a);
benzene (5 mL), and the solution was added to a stirred suspenꢀ
sion of MeONa (0.19 g, 3.5 mmol) in benzene (5 mL) under
argon at 20 C. The reaction mixture was allowed to stand for 2 h
and then diluted with MeOBut and water. The organic layer was
separated, and the aqueous layer was neutralized with 10% HCl
and extracted with MeOBut. The extract was washed with water
and a saturated NaCl solution, dried with Na2SO4, and concenꢀ
trated in vacuo. The residue was chromatographed on a column
with silica gel. The elution with a 1 : 1 petroleum ether—MeOBut
mixture gave a mixture of oximes 8a/b in a ratio of ~4/1 (TLC
and 1H NMR data) in a yield of 0.39 g (75%).
synꢀ(2S*,6S*)ꢀ2ꢀtertꢀButyl(dimethyl)silyloxyꢀ (9a) and antiꢀ
(2S*,6S*)ꢀ2ꢀtertꢀbutyl(dimethyl)silyloxyꢀ6ꢀhydroxymethylꢀ1ꢀhyꢀ
droxyiminocyclohexane (9b). Method A. A solution of isoxazoliꢀ
dine 7 (1 g, 2.9 mmol) in THF (7 mL) was added to a vigorously
stirred suspension of KF (0.25 mg, 4.3 mmol) in MeOH (8 mL)
under argon at –65 C. The reaction mixture was stirred at –65 C
for 20 min. Then the mixture was warmed to 20 C, allowed to
stand for 12 h, and concentrated in vacuo. The residue was treatꢀ
ed with EtOAc and water. The organic layer was separated,
washed with water and a saturated NaCl solution, dried with
Na2SO4, and concentrated in vacuo. The residue was chromatoꢀ
graphed on a column with silica gel. The elution with a 3 : 2
petroleum ether—MeOBut mixture gave a mixture of oximes 9a/9b
in a ratio of ~3/2** as a white amorphous powder in a yield of
0.32 g (40%). IR (KBr), /cm–1: 617, 778, 835, 950, 982, 1039,
1082, 1109, 1135, 1256, 1363, 1415, 1462, 2858—2946, 3126—3426.
Highꢀresolution MS (ESI), found: m/z 274.1836 and 296.1651;
C13H27NO3Si; calculated: m/z 274.1833 [M + H]+ and 296.1652
[M + Na]+.
1H NMR (200.13 MHz), : 0.06 (s, 6 H, Me2Si); 0.10 (s, 6 H,
Me2Si) (9a); 0.12 and 0.17 (both s, 3 H each, Me2Si) (9b); 0.90
(s, 9 H, Me3CSi); 1.15—2.16 (m, 6 H, H2C(3), H2C(4), H2C(5));
2.83 (m, 1 H, HC(6); 3.66—3.87 (m, 2 H, H2CO); 4.76 (dd, 1 H,
HC(2), J = 2.8 Hz, J = 2.8 Hz) (9b); 5.35 (dd, 1 H, HC(2),
J = 2.8 Hz, J = 2.8 Hz) (9a). 13C NMR (50.03 MHz), : –5.1,
–5.0, and –4.7 (Me2Si); 17.9 (Me3CSi) (9a), 18.2 (9b); 19.0 (9a),
19.8 (9b) (C(4)); 25.8 (9a), 25.9 (9b) (CMe3); 28.5 (9b), 30.3
(9a) C(5); 34.2 (9b), 34.4 (9a) (C(3)); 39.9 (9a), 40.3 (9b) (C(6);
63.8 (9a), 64.7 (9b) (CH2OH); 69.8 (9a), 71.0 (9b) (C(2)); 160.1
(9b), 163.3 (9a) (C=NOH).
Method B. A solution of isoxazolidine 7 (1.38 g, 4 mmol) in
benzene (5 mL) was added to a stirred suspension of MeONa
(0.38 g, 7 mmol) in benzene (10 mL) under argon at 20 C. The
reaction mixture was allowed to stand for 2 h and then diluted
with MeOBut and water, neutralized with 5% HCl, and extractꢀ
ed with MeOBut. The extract was washed with water and a satuꢀ
rated NaCl solution, dried with Na2SO4, and concentrated
in vacuo. The residue was chromatographed on a column with
silica gel. The elution with a 4 : 1 petroleum ether—MeOBut
mixture gave a mixture of oximes 9a/9b in a ratio of ~4/1 (TLC
and 1H NMR data) in a yield of 0.84 g (77%); the spectral charꢀ
acteristics of this mixture are virtually the same as those deꢀ
scribed above.
1
0.10 and 0.12 (both s, 3 H each, Me2Si) (8b); 0.88 (s, 9 H,
Me3CSi) (8b); 0.89 (s, 9 H, Me3CSi) (8a); 1.30—1.76 (m, 2 H,
H2C(4)); 1.91—2.12 (m, 2 H, H2C(3)); 2.91 (m, 1 H, HC(5))
(8b); 3.16 (m, 1 H, HC(5)) (8a); 3.63 (dd, 1 H, HaCO, J = 10.5 Hz,
J = 6.9 Hz); 3.78 (dd, 1 H, HbCO, J = 10.5 Hz, J = 4.1 Hz); 4.51
(br.t, 1 H, HC(2), J = 7.4 Hz) (8a); 4.90 (m, 1 H, HC(2)) (8b);
6.20 (br.s, 1 H, OH). 13C NMR (50.03 MHz), : –4.9, –4.8,
–4.6 (Me2Si); 18.0 (Me3CSi); 23.5 (8a), 24.1 (8b) (C(4)); 25.7
(8b), 25.8 (8a) (CMe3); 33.1 (8a), 33.8 (8a) (C(3)); 41.9 (8a),
42.6 (8b) (C(5); 64.0 (CH2OH); 69.0 (C(2)) (8b); 73.9 (C(2))
(8a); 165.7 (C=NOH).
Individual components of a mixture of 8a,b were isolated by
crystallization of chromatographic fractions enriched in a parꢀ
ticular component.
Oxime 8a was obtained as colorless crystals with m.p.
128—130 C (MeOBut—petroleum ether). IR (KBr), /cm–1
:
668, 773, 838, 951, 988, 1034, 1063, 1099, 1149, 1257, 1361, 1463,
1473, 1680, 2857—2955, 3114, 3200. Highꢀresolution MS (ESI),
m/z: found 260.1684 and 282.1498; calculated for C12H25NO3Si,
m/z: 260.1676 [M + H]+ and 282.1496 [M + Na]+.
Oxime 8b was obtained as colorless crystals with m.p. 96—98 C
(MeOBut—petroleum ether). IR (KBr), /cm–1: 676, 779, 833,
976, 1032, 1074, 1111, 1253, 1338, 1461, 1474, 1676, 2858—2952,
3251. Highꢀresolution MS (ESI), found: m/z 260.1673 and
282.1487; C12H25NO3Si; calculated: m/z: 260.1676 [M + H]+
and 282.1496 [M + Na]+.
The further elution with EtOAc gave a mixture of isomers
8c/8d in a ratio of ~1 : 1 (1H NMR data) in a yield of 210 mg
(33%). 1H NMR (200.13 MHz, CD3CN), : 1.36—1.67 (m, 2 H,
H2C(4)); 1.85—2.12 (m, 2 H, H2C(3)); 2.75 (m, 1 H, HC(5)) (8d);
3.05 (m, 1 H, HC(5)) (8c); 3.48 (dd, 1 H, HCO, J = 10.2 Hz,
J = 6.7 Hz) (8d); 3.59 (m, HaCO) (8c, 8d); 3.69 (dd, 1 H, HbCO,
J = 10.5 Hz, J = 4.8 Hz) (8c); 4.35 (br.t, 1 H, HC(2), J = 7.6 Hz)
(8c); 4.77 (td, 1 H, HC(2), J = 7.6 Hz, J = 3.2 Hz) (8d); 8.83
(br.s, OH). 13C NMR (50.03 MHz, CD3CN), : 24.4 (8c), 25.6
(8d) (C(4)); 32.4 (8d), 33.3 (8c) (C(3)); 42.6 (8c), 44.8 (8d)
(C(5); 62.4 (CH2OH) (8c); 63.9 (CH2OH) (8d); 70.7 (C(2))
(8d); 73.4 (C(2)) (8c); 166.8 (C=NOH).
Individual components of a mixture of 8c,d were isolated by
crystallization of chromatographic fractions enriched in a parꢀ
ticular component.
Oxime 8c was obtained as colorless crystals with m.p.
104—106 C (MeOBut). IR (KBr), /cm–1: 619, 742, 871, 942,
967, 1020, 1042, 1153, 1229, 1261, 1317, 1360, 1438, 1464, 1666,
2885, 2942, 2978, 3279. Highꢀresolution MS (ESI), found: m/z
146.0814 and 168.0634; C12H25NO3Si; calculated: m/z: 146.0812
[M + H]+ and 168.0631 [M + Na]+.
Oxime 8d was obtained as colorless crystals with m.p.
121—123 C (EtOAc). IR (KBr), /cm–1: 631, 756, 803, 930,
954, 994, 1062, 1152, 1262, 1332, 1436, 1672, 2865, 2973,
3095—3323. Highꢀresolution MS (ESI), found: m/z 168.0634;
C12H25NO3Si; calculated: m/z 168.0631 [M + Na]+.
Method B. A mixture of compound 1b (0.5 g, 2.0 mmol),
HMDS (2.5 mL), Et3N (0.22 g, 2.2 mmol), and HMPA (70 mg,
0.4 mmol) was heated with stirring under argon at 110 C for 5 h
and then concentrated in vacuo. The residue was dissolved in
(2S*,5R*)ꢀ2ꢀtertꢀButyl(dimethyl)silyloxyꢀ5ꢀhydroxymethylꢀ
cyclopentanone (10). A mixture of oximes 8a,b (~4 : 1, 0.13 g,
0.5 mmol) and HIO4•2 H2O (57 mg, 0.25 mmol) was thoroughꢀ
ly stirred and triturated in an agate mortar for 3 min. The resultꢀ
* The ratio of isomers 8a,b in a solution in CDCl3 upon storage
** The ratio of isomers 9a,b in a solution in CDCl3 upon storage
for 2 h after the dissolution is given.
for 40 min after the dissolution is given.

700
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 3, March, 2014
Lozanova et al.
ing oily substance was extracted with MeOBut. The extract was
filtered through a short layer of SiO2 and concentrated in vacuo.
The residue was chromatographed on a column with silica gel.
The elution with a 1 : 1 petroleum ether—MeOBut mixture gave
ketone 10 in a yield of 104 mg (85%) as a colorless oil with
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 13ꢀ03ꢀ00197).
References
Rf 0.45 (petroleum ether—MeOBut, 1 : 1). IR (thin layer), /cm–1
:
780, 838, 985, 1065, 1129, 1255, 1362, 1464, 1664, 1748,
2858—2955, 3432. Highꢀresolution MS (ESI), found: m/z 245.1572
and 267.1388; C12H24O3Si; calculated: m/z: 245.1567 [M + H]+
and 267.1387 [M + Na]+. 1H NMR (200.13 MHz), : 0.09 (s, 3 H,
MeaSi); 0.13 (s, 3 H, MebSi); 0.90 (s, 9 H, Me3CSi); 1.68 (m, 2 H,
H2C(4)); 2.02—2.41 (m, 3 H, H2C(3), HC(5)); 3.67 (dd, 1 H,
HCO, J = 10.9 Hz, J = 5.5 Hz); 3.85 (dd, 1 H, H´CO, J = 10.9 Hz,
J = 4.8 Hz); 3.98 (dd, 1 H, HC(2), J = 10.6 Hz, J = 8.1 Hz).
13C NMR (50.03 MHz), : –5.2, –4.7 (Me2Si); 19.9 (C(4));
25.7 (Me3CSi); 30.4 (C(3)); 48.2 (C(5); 61.8 (CH2OH); 76.8
(C(2)); 218.0 (C=O).
(2S*,6R*)ꢀ2ꢀtertꢀButyl(dimethyl)silyloxyꢀ6ꢀhydroxymethylꢀ
cyclohexanone (11). A product was obtained analogously to that
described above from a mixture of oximes 9a,b (~3 : 2, 136 mg,
0.5 mmol) and HIO4•2H2O (57 mg, 0.25 mmol). The product
was chromatographed on a column with silica gel. The elution
with a 4 : 1 petroleum ether—MeOBut mixture gave ketone 11 in
a yield of 110 mg (85%) as a colorless oil with Rf 0.46 (petroleum
ether—MeOBut, 7 : 3). IR (thin layer), /cm–1: 675,780, 839,
911, 940, 1045, 1112, 1255, 1361, 1390, 1463, 1558, 1717,
2858—2951, 3434. Highꢀresolution MS (ESI), found: m/z 259.1720
and 281.1537; C13H26O3Si; calculated: m/z 259.1724 [M + H]+
and 281.1543 [M + Na]+. 1H NMR (200.13 MHz), : 0.04 (s, 3 H,
MeaSi); 0.08 (s, 3 H, MebSi); 0.91 (s, 9 H, Me3CSi); 1.34—2.15
(m, 6 H, H2C(3), H2C(4), HC(5)); 2.27 (m, 1 H, OH); 3.12 (dd,
1 H, HC(6), J = 11.0 Hz, J = 6.4 Hz, J = 6.1 Hz, J = 4.2 Hz);
3.66 (dd, 1 H, HCO, J = 11.3 Hz, J = 4.2 Hz); 3.74 (dd, 1 H,
H´CO, J = 11.3 Hz, J = 6.4 Hz); 4.02 (dd, 1 H, HC(2), J = 3.6 Hz,
J = 2.5 Hz). 13C NMR (50.03 MHz), : –5.0, –4.9 (Me2Si); 18.1
(CMe3); 19.9 (C(4)); 25.7 (Me3CSi); 30.6 (C(5)); 36.2 (C(3));
47.9 (C(6); 62.4 (CH2OH); 75.7 (C(2)); 214.5 (C=O).
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Received November 28, 2013