Oxidative and hydrolytic cleavage of cyclopropane and spirocyclobutane derivatives of 6,8-dioxabicyclo[3.2.1]octane, the products of transformation of levoglucosenone

Article abstract of DOI:10.1007/s11172-010-0336-4

A new method for the synthesis of (1R,4S,5S)-4-hydroxymethyl-3- oxabicyclo[3.1.0]hexan-2-one, the cyclopropane analog of (S)-5-hydroxypent-2-en- 4-olide, has been suggested based on oxidation of (1S,2S,4R,6R)-7,9- dioxatricyclo[4.2.1.0^2,4]nonan-5-one. Oxidation of cyclobutanones, spirojoined with the fragments of 6,8-dioxabicyclo[3.2.1]oct-2-ene, 6,8-dioxabicyclo[3.2.1]octane (at position 4), or 7,9-dioxatricyclo[4.2.1.0 ^2,4]nonane (at position 5), upon the action of m-chloroperoxybenzoic acid or the KMnO₄-H₂SO₄-H₂O system leads to the corresponding spirojoined butanolides in 73-85% yields. The same cyclobutanones easily undergo the four-membered ring opening upon the action of dilute H₂SO₄ at 50-90 °C to form 6,8-dioxabicyclo[3.2. 1]octane-4-or 7,9-dioxatricyclo[4.2.1.0^2,4]nonane-5-propionic acid.

Full text of DOI:10.1007/s11172-010-0336-4

1
930
Russian Chemical Bulletin, International Edition, Vol. 59, No. 10, pp. 1930—1936, October, 2010
Oxidative and hydrolytic cleavage of cyclopropane
and spirocyclobutane derivatives of 6,8ꢀdioxabicyclo[3.2.1]octane,
the products of transformation of levoglucosenone
R. A. Novikov, R. R. Rafikov, E. V. Shulishov, and Yu. V. Tomilov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
4
7 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6390. Eꢀmail: tom@ioc.ac.ru
A new method for the synthesis of (1R,4S,5S)ꢀ4ꢀhydroxymethylꢀ3ꢀoxabicyclo[3.1.0]hexanꢀ
ꢀone, the cyclopropane analog of (S)ꢀ5ꢀhydroxypentꢀ2ꢀenꢀ4ꢀolide, has been suggested based
2
2
,4
on oxidation of (1S,2S,4R,6R)ꢀ7,9ꢀdioxatricyclo[4.2.1.0 ]nonanꢀ5ꢀone. Oxidation of cycloꢀ
butanones, spirojoined with the fragments of 6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀene, 6,8ꢀdiꢀ
oxabicyclo[3.2.1]octane (at position 4), or 7,9ꢀdioxatricyclo[4.2.1.02,4]nonane (at position 5),
upon the action of mꢀchloroperoxybenzoic acid or the KMnO —H SO —H O system leads to
4
2
4
2
the corresponding spirojoined butanolides in 73—85% yields. The same cyclobutanones easily
undergo the fourꢀmembered ring opening upon the action of dilute H SO at 50—90 °C to form
2
4
2
,4
6
,8ꢀdioxabicyclo[3.2.1]octaneꢀ4ꢀ or 7,9ꢀdioxatricyclo[4.2.1.0 ]nonaneꢀ5ꢀpropionic acid.
Key words: 7,9ꢀdioxatricyclo[4.2.1.02,4]nonanꢀ5ꢀone, 3ꢀoxabicyclo[3.1.0]hexanꢀ2ꢀones,
spiro{6,8ꢀdioxabicyclo[3.2.1]octaneꢀ4,2´ꢀcyclobutanones}, spiro compounds, γꢀlactones,
oxidation, hydration, cyclobutanones, levoglucosenone.
The structure of levoglucosenone (1) and its derivaꢀ
Scheme 1
tives contains dioxolane and pyranone fragments, which
1
can undergo hydrolytic and oxidative cleavage. The study
2
of oxidation of compound 1 with peroxy acids showed
that the first compound to isolate is (S)ꢀ5ꢀformyloxyꢀ
pentꢀ2ꢀenꢀ4ꢀolide (2), whose acidic cleavage gives valuꢀ
able product, (S)ꢀ5ꢀhydroxypentꢀ2ꢀenꢀ4ꢀolide (3) conꢀ
taining one chiral center in the molecule (Scheme 1). Penꢀ
tenolide 3 is used in the production of some mediꢀ
cines (burseran and isostegan), antibiotic lasalocide A,
3
—5
pheromones, surrogate of whisky and brandy odor.
Similarly, the Baeyer—Villiger oxidation of dihydrolevoꢀ
1
2
glucosenone 4 (R = R = H) and its hydroxy derivative 4
1
2
(
5
R = OH, R = H) led to (S)ꢀ5ꢀhydroxypentanꢀ4ꢀolides
1
2
3
2,6
(R = H, OH; R = R = H), whereas oxidation of
tricyclic ketones obtained by the Diels—Alder reaction
of levoglucosenone (1) and 1,3ꢀbutadiene or isoprene led
1
2
to fused formyloxypentꢀ2ꢀenꢀ4ꢀolides 5 (R + R
=
ed 5ꢀhydroxypentanꢀ4ꢀolides with the fused cyclopropane
fragment in the molecule, 6ꢀsubstituted (1S,4S,5S,6S)ꢀ4ꢀ
3
=
CH CH=CHCH , CH CMe=CHCH ; R = CHO) in
2
2
2
2
1,2
7
,8
high yields. The authors of the works consider that
the formation of formates is due to the acidꢀcatalyzed
rearrangement of the intermediate bicyclic ortho esters
hydroxymethylꢀ3ꢀoxabicyclo[3.1.0]hexanꢀ2ꢀones
(Scheme 2).
7
Thus, the ring openings in the levoglucosenone moleꢀ
cule (1) and its derivatives can serve as a good strategy for
the synthesis of substituted γꢀlactones with certain configꢀ
uration of chiral centers in the molecule.
(
see Scheme 1).
Recently, oxidation of dioxatricyclo[4.2.1.02,4]nonanꢀ
ꢀones (6)10 with hydrogen peroxide in acetic acid affordꢀ
9
5
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1880—1886, October, 2010.
066ꢀ5285/10/5910ꢀ1930 © 2010 Springer Science+Business Media, Inc.
1

Oxidation of levoglucosenone derivatives
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
1931
Scheme 2
of dilute H SO gives (1R,4S,5S)ꢀ4ꢀhydroxymethylꢀ3ꢀ
2 4
oxabicyclo[3.1.0]hexanꢀ2ꢀone (12) in quantitative yield.
The same compound was also obtained by the direct oxiꢀ
dation of ketone 8 upon the action of activated manganese
dioxide in 5% aq. H SO .
3
0% H O
2 2
2
4
We also showed that bicyclic lactone 12 can be obꢀ
tained in up to 76% yield in one experimental step starting
from tricyclic hydroxy acetal 10. The reaction was carried
out at 20 °C for 1 h, using KMnO in 5% aq. sulfuric acid
4
as an oxidant at the ratio oxidant : substrate = 2 : 1 (an
increased amount of KMnO causes further oxidation of
4
product 12 to cisꢀcyclopropaneꢀ1,2ꢀdicarboxylic acid).
Bicyclic lactone 12 is of interest as a chiral block for
the synthesis of various biologically active compounds, in
particular, for the preparation of cyclopropaneꢀcontainꢀ
ing amino acids and cyclopropane carbocyclic nucleoꢀ
1
2,13
sides.
R = aryl, hetaryl, 1ꢀadamantyl, OEt
Earlier, chiral lactone 12 has been obtained in six steps
in ∼ 33% total yield from the optically active Dꢀglyceraldeꢀ
1
2
Results and Discussion
hyde acetonide. It should be noted that lactone 12 obꢀ
tained by this method is not apparently an individual comꢀ
pound, since its melting point is by 10 °C below than that
of the sample obtained by us (see Experimental), and the
In the present work, we studied oxidation and hydrolyꢀ
sis of some new levoglucosenone derivatives, in particular,
cyclopropane derivative 8, as well as 6,8ꢀdioxabicycloꢀ
13
12
C NMR spectrum published in the work contained an
additional signal at δ 29.6.
[
3.2.1]octanes spirojoined with cyclobutanone fragment
In the absence of oxidant, acidic hydrolysis of tricyclic
(
see below). Tricyclic ketone 8 can be easily obtained by
hydroxy acetal 10 (5% H SO , 40 °C) proceeds nonselecꢀ
catalytic cyclopropanation of (1S,4S,5R)ꢀ6,8ꢀdioxabiꢀ
cyclo[3.2.1]octꢀ2ꢀenꢀ4ꢀol (9) with diazomethane in the
presence of Pdꢀcatalyst and subsequent oxidation of obꢀ
tained dioxatricyclononanol 10 upon the action of freshly
2
4
tively and gives a mixture of difficult to identify alcohols.
To increase the selectivity of the process, we converted
alcohol 10 to ether 13 by methylation with diazomethane
1
1
in the presence of HBF . Acetolysis of the dioxolane fragꢀ
prepared MnO or the RuCl —NaIO system.
4
2
3
4
ment in compound 13 in the presence of pꢀtoluenesulfonꢀ
ic acid gives stereoisomeric 4ꢀacetoxyꢀ3ꢀoxabicycloꢀ
Under mild conditions (25 °C, 4 days), the Baeyer—Vilꢀ
liger oxidation of ketone 8 with mꢀchloroperoxybenzoic
acid (MCPBA) gives up to 70% yield of bicyclic formate
[
4.1.0]heptanes 14 in high yield (Scheme 4) with preserꢀ
vation of configuration of substituents at C(2) and C(5).
1
1 (Scheme 3). Hydrolysis of formate 11 upon the action
Scheme 4
Scheme 3
Reagents and conditions: i. CH N , HBF , Et O, CH Cl , 20 °C;
2
2
4
2
2
2
ii. TsOH•H O, Ac O, 20 °C, 24 h.
2
2
Further, we studied a possibility of oxidation and
hydrolysis of 6,8ꢀdioxabicyclo[3.2.1]octanes spirojoined
with the cyclobutanone fragment. The starting cyclobuꢀ
tanones 15—17 (see Schemes 5—7) were obtained by the
reaction of levoglucosenone (1), dihydrolevoglucosenone
1
2
4
(R = R = H), or tricyclononanone 8 with the in situ
Reagents and conditions: i. CH N , Pd(acac) , 10 °C; ii. MnO
2
2
2
2
or RuCl —NaIO , CH Cl , 20 °C; iii. MCPBA, 20 °C; iv. MnO ,
generated diazocyclopropane and subsequent isomerizaꢀ
tion of oxaspiropentanes formed to cyclobutanones.
3
4
2
2
2
1
4,15
5
% H SO , 20 °C, 48 h; v. KMnO (2 equiv.), 5% H SO , 20 °C, 1 h.
2
4
4
2
4

1
932
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
Novikov et al.
The Baeyer—Villiger oxidation16 of unsaturated keꢀ
Scheme 6
tone (1S,4S,5R)ꢀ15 with 30% molar excess of MCPBA in
dichloromethane (25 °C, 5 h) provides the virtually full
conversion of the starting ketone 15, which under these
conditions is stereoselectively transformed to the spiroꢀ
joined lactone (1S,4S,5R)ꢀ18 and partially to epoxide 19
i or ii
(
Scheme 5). The use of a threeꢀfold excess of MCPBA
results in the increase of the amount of epoxide 19, howꢀ
ever, epoxidation proceeds much slower than lactonizaꢀ
tion, and even after 5 days the yield of compound 19 did
not exceed 70%.
Scheme 5
Reagents and conditions: i. MCPBA, CH Cl , 20 °C, 10 h;
2
2
ii. KMnO , 5% H SO , 20 °C, 6—7 min; iii. 10% H SO , 50 °C,
4
2
4
2
4
1
0 min.
If the oxidant is absent, hydrolysis of compound 16
upon the action of 10% aq. H SO leads to the isomeric
Molar ratio
Yield (%)
2
4
2
,4
1
1
1
5 : MCPBA
: 1.3
18
82
23
19
8
70
3ꢀ(7,9ꢀdioxatricyclo[4.2.1.0 ]nonꢀ5ꢀyl)propionic acids
1
13
2
1 in the ratio 4.2 : 1. According to the H and C NMR
: 3.0
spectra, both isomers have the sameꢀtype set of signals,
and the character of the highꢀfield signals (δ 0.4—1.1) and
the lowꢀfield signals (δ 3.7—5.1) unambiguously evidence
that the cyclopropane and dioxolane fragments in the molꢀ
ecule remain. The splitting of the signals for the methine
protons at C(6) shows that the vicinal spinꢀspin coupling
constant J5,6 in the major isomer is about 1.0 Hz, whereas
in the minor — 3.0 Hz. Taking into account that in the
bicyclo[3.2.1]octane framework, the spinꢀspin coupling
constant J1,2ꢀexo or J4ꢀexo,5 is larger than J1,2ꢀendo or
J4ꢀendo,5, it can be suggested that the major isomer correꢀ
sponds to the antiꢀorientation of the alkyl substituent with
respect to the anhydro bridge.
The structure of lactones 18 and 19 was established
1
13
based on the H and C NMR spectra of their mixtures
obtained in two different experiments (attempted separaꢀ
tion of the lactones by crystallization from benzene or
chromatography on SiO failed and virtually produced no
2
1
change in their ratio). In the H NMR spectrum of the
spirojoined lactone 18, the chemical shifts and spinꢀspin
coupling constant for the protons of the dioxabicycloꢀ
3.2.1]octene fragment are similar to the corresponding
signals of the starting compound 15. In the spectrum of
oxirane 19, the signals for the protons at C(2) and C(4) are
[
3
3
found as doublet of doublets with J = 4.0, J = 1.3,
2
,4
1,2
4
Similar transformations are also observed in the case
of (1S,4S,5R)ꢀspiro(6,8ꢀdioxabicyclooctaneꢀ4,2´ꢀcycloꢀ
butanone) (17). The action of MCPBA, as it was expectꢀ
ed, leads to the spirojoined lactone 1S,4S,5Rꢀ22 with high
stereoselectivity (Scheme 7). However, oxidation of cycloꢀ
butanone 17 upon the action of the KMnO —H SO sysꢀ
and J = 2.5 Hz, that by analogy with the oxiranes of
4
,6
1
7
close structure evidences the antiꢀconfiguration of the
oxirane ring with respect to the anhydro bridge. For
comparison, in the structures of 3,7,9ꢀtrioxatricycloꢀ
4.2.1.0 ]nonanes containing a synꢀoxirane ring, the spinꢀ
spin coupling constant J is about 4.6 Hz.
2,4
[
3
18
4
2
4
1
,2
tem or acid hydrolysis at 90 °C proceed nonstereoselecꢀ
tively and in both cases give mixtures of two stereoisomeric
lactones 22 or substituted propionic acids 23 in the ratio
Treatment of (1S,2S,4R,5S,6R)ꢀspiro(7,9ꢀdioxatricyꢀ
clononaneꢀ5,2´ꢀcyclobutanone) (16) with 1.5ꢀfold molar
excess of MCPBA leads to the spirojoined lactone 20 with
high stereoselectivity (90% yield) (Scheme 6). The same
lactone 20 can be also obtained in 72% yield by oxidation
of cyclobutanone 16 with equimolar amount of KMnO4
in acidic medium and in this case, the reaction comes to
completion within several minutes. It cannot be excluded
that in this case the process is somewhat less selective,
that follows from the presence of considerable number of
∼
3 : 1, which are difficult to separate by chromatography
on SiO2.
A plausible mechanism of the transformations deꢀ
scribed under conditions of acid hydrolysis or oxidation
upon the action of KMnO is given in Scheme 8. In the
4
first step, the oxygen atom of the dioxolane ring is protoꢀ
nated, with the oxonium cation A formed being in the
equilibrium with carbocation B. Further, the fourꢀmemꢀ
bered ring is opened to form unsaturated acylium cation
C, which, depending on the reaction conditions, either
1
13
signals for impurities in the H and C NMR spectra of
the reaction mixture, however, chromatography on SiO2
yielded compound 20 in the individual state.

Oxidation of levoglucosenone derivatives
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
1933
Scheme 7
tion of considerable amount of the isomer of vicinal diol,
in which the hydroxy groups after elimination of MnO2
are in transꢀposition to the fused cyclopropane fragment
hindering one of the sides of the plane of the double bond
in the sixꢀmembered ring. On protonation, this factor is
not apparently already so important, that results in the
formation of two stereoisomeric acids 21.
It should be noted that asymmetric center at C(1) in
all the transformations considered was preserved. Taking
into account the high stereoselectivity of the oxidation
processes of the cyclopropane analog of levoglucosenone
8
and spirojoined cyclobutanones 15—17, the compounds
obtained can be of interest as synthetic blocks with the
preset configuration of chiral centers in the molecule.
Experimental
Reagents and conditions: i. 15% H SO , 90 °C, 10 min; ii. MCPBA,
2
4
1H and 13C NMR spectra were recorded on Bruker AVANCE
II 300 (300 and 75.5 MHz, respectively) and Bruker DRXꢀ500
CH Cl , 20 °C, 10 h; iii. KMnO , 5% H SO , 40 °C, 6—7 min.
2
2
4
2
4
spectrometers (500 and 125.3 MHz, respectively) in CDCl or
3
DMSOꢀd containing 0.05% of Me Si as an internal standard;
adds a proton under conditions of acid hydrolysis (D), or
is hydroxylated upon the action of potassium permanganꢀ
ate (E). The formation of isomeric acids 23 or spirojoined
lactones 22 can be explained by addition of a proton or
a permanganate ion from different sides of the plane of the
double bond in the intermediate C. In the transformations
under consideration, the initial protonation and the
dioxolane ring opening are the factors promoting further
convertion of the cyclobutanone fragment, which on its
own is fairly stable under these conditions.
6
4
the COSY, NOESY, HSQC, and HMBC experiments were perꢀ
formed on a Bruker DRXꢀ500 spectrometer. Mass spectra were
recorded on a Finnigan MAT INCOSꢀ50 (EI, 70 eV, direct
inlet) and Finnigan LCQ instruments (ESI). Optical rotation
was measured on a Perkin—Elmer 341 MC polarimeter at 20 °C
(
λ 589 nm, in a 2.5ꢀcm cuvette). Thinꢀlayer chromatography
was performed on Silicagel 60 plates (Merck) with visualization
in iodine vapors. Preparative separation was performed by column
or thinꢀlayer chromatography (silica gel 60, 0.040—0.063 mm,
Merck) with the ratio substance : sorbent ∼ 1 : 100. (1S,2S,4R,6R)ꢀ
2
,4
11
7
7
,9ꢀDioxatricyclo[4.2.1.0 ]nonanꢀ5ꢀone (8), (1S,2S,4R,5S,6R)ꢀ
Unlike compound 17, oxidation of cyclobutanone 16
with potassium permanganate in acidic medium, as it
was previously mentioned, mainly gives lactone
,9ꢀdioxatricyclo[4.2.1.02 ]nonanꢀ5ꢀol (10), (1S,4S,5R)ꢀ
,4
11
spiro{6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀenꢀ4,2´ꢀcyclobutanone}
1
4
2,4
(
15), (1S,2S,4R,5S,6R)ꢀspiro{7,9ꢀdioxatricyclo[4.2.1.0 ]ꢀ
(
1S,2S,4R,5S,6R)ꢀ20. Apparently, in the first steps leadꢀ
15
nonaneꢀ5,2´ꢀcyclobutanone} (16), and (1S,4S,5R)ꢀspiro{6,8ꢀ
dioxabicyclo[3.2.1]octaneꢀ4,2´ꢀcyclobutanone} (17) were synꢀ
ing to the intermediate similar to cation C, the mechaꢀ
nism is as suggested above, however, the hydroxylation
upon the action of permanganate ion leads to the formaꢀ
15
thesized according to the described procedures. Active mangaꢀ
nese dioxide was obtained by addition of a solution of mangaꢀ
Scheme 8

1
934
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
Novikov et al.
nese sulfate and NaOH to a hot solution of potassium permangaꢀ
MgSO . After the solvents were evaporated, the product was
4
nate.19 mꢀChloroperoxybenzoic acid (MCPBA) and HBF •OEt2
purified by column chromatography on SiO (benzene—AcOEt,
4
2
were purchased from Aldrich. Solvents of chemically pure grade
1 : 3) to obtain lactone 12 (68 mg, 76%) as colorless crystals;
whose physicoꢀchemical parameters were analogous to those of
the sample obtained in method A.
(
>99.5%) were used without additional purification.
1R,4S,5S)ꢀ2ꢀFormyloxymethylꢀ3ꢀoxabicyclo[3.1.0]hexanꢀ
ꢀone (11). mꢀChloroperoxybenzoic acid (173 mg, 1 mmol) was
(
4
(1S,2S,4R,5S,6R)ꢀ5ꢀMethoxyꢀ7,9ꢀdioxatricyclo[4.2.1.02,4]ꢀ
added to a solution of ketone 8 (99 mg, 0.7 mmol) in CH Cl
nonane (13). The compound HBF •OEt2 (80 mg, 0.5 mmol)
2
2
4
(
4 mL) with stirring, after 4 days the reaction mixture was neuꢀ
was added to a solution of tricyclic alcohol 10 (5.69 g, 40 mmol)
tralized with aqueous NaHCO . The organic layer was separatꢀ
in CH Cl (60 mL), followed by a dropwise addition of an etheꢀ
3
2
2
ed, the aqueous layer was extracted with dichloromethane
real solution of diazomethane (0.56 M, 100 mL, 56 mmol) to the
reaction mixture with stirring at 15 °C over 1 h and the mixture
was stirred for additional 1 h. After the solvent was evaporated,
the residue was distilled in vacuo to obtain methoxy derivative 13
(
2×4 mL), dried with anhydrous MgSO4 and concentrated
in vacuo. Preparative TLC on SiO2 (benzene—AcOEt, 5 : 1)
yielded compound 11 (76 mg, 70%) as colorless oil, R 0.4. MS,
f
m/z (Irel (%)): 156 [M] (40), 139 [M – OH]+ (31), 110 (28),
+
(5.75 g, 92%) as colorless oil, b.p. 51—53 °C (0.05 Torr), [α]D
20
1
9
7 (100), 69 (17). H NMR (CDCl ), δ: 0.93 (ddd, 1 H, synꢀH(6),
–83.9 (c 0.47; CHCl ). Found (%): C, 61.34; H, 7.97. C H O .
3
3
8
12
3
2
3
J = 5.1 Hz, J = 3.9 Hz and 4.0 Hz); 1.31 (ddd, 1 H, antiꢀH(6),
J = 5.1 Hz, J = 8.3 Hz); 2.15 (m, 2 H, H(1) and H(5)); 4.36
ddd, 2 H, CH O, J = 4.3 Hz, J = 1.0 Hz); 4.58 (br.t, 1 H,
H(2), J = 4.3 Hz); 8.11 (q, 1 H, CHO, J = 1.0 Hz). C NMR
Calculated (%): C, 61.52; H, 7.74. MS, m/z (Irel (%)): 125 (3),
113 (22), 110 (95), 95 (33), 79 (44), 67 (96), 45 (93), 41 (100).
2
3
3
4
1
3
3
2
(
H NMR (CDCl ), δ: 0.48 (ddd, 1 H, synꢀH(3), J = 4.9 Hz,
2
3
3
13
2
J = 5.0 Hz and 5.2 Hz); 0.69 (ddd, 1 H, antiꢀH(3), J = 4.9 Hz,
3
(
CDCl ), δ: 11.7 (C(6)), 17.4 (C(5)), 19.6 (C(1)), 64.6 (CH O),
J = 8.0 Hz, J = 9.1 Hz); 0.91 and 1.02 (both m, 1 H each,
3
2
3
7
7.3 (C(2)), 160.3 (CHO), 175.1 (C=O).
(H(2) and H(4)); 3.33 (br. d, 1 H, H(5), J = 3.1 Hz); 3.47 (s, 3 H,
OMe); 3.85 (dd, 1 H, exoꢀH(8), J = 6.8 Hz, J = 4.1 Hz); 4.10
(d, 1 H, endoꢀH(8), J = 6.8 Hz); 4.61 (br. d, 1 H, H(1), J = 4.1 Hz);
5.29 (br. dd, 1 H, H(6), J = 3.1 Hz, J = 1.5 Hz). C NMR
2
3
(
1R,4S,5S)ꢀ4ꢀHydroxymethylꢀ3ꢀoxabicyclo[3.1.0]hexanꢀ2ꢀ
2
3
one (12). A. Concentrated hydrochloric acid (0.1 mL) was addꢀ
ed to a solution of formate 11 (63 mg, 0.45 mmol) in the
CH Cl —MeOH (1 : 1) solvent mixture (3 mL) and the mixture
3
4
13
(CDCl ), δ: 6.9 (C(3)), 9.9 (C(4)), 14.6 (C(2)), 56.8 (OMe), 70.9
2
2
3
was stirred for 5 h at 40 °C, followed by addition of some anhyꢀ
(C(8)), 71.2 (C(1)), 77.0 (C(5)), 98.1 (C(6)).
drous MgSO . The solvents were evaporated in vacuo to obtain
(1S,2S,4S,5S,6R)ꢀ and (1S,2S,4R,5S,6R)ꢀ2ꢀAcetoxymethꢀ
ylꢀ4ꢀacetoxyꢀ5ꢀmethoxyꢀ3ꢀoxabicyclo[4.1.0]heptanes (14).
pꢀToluenesulfonic acid monohydrate (0.76 mg, 0.4 mmol) was
added to a solution of 5ꢀmethoxyꢀ7,9ꢀdioxatricyclo[4.2.1.0 ]ꢀ
nonane (13) (0.63 g, 4 mmol) in acetic anhydride (12 mL) with
stirring. After 24 h, the brownish claretꢀcolored reaction mixture
was concentrated without heating in high vacuo and the residue
4
lactone 12 (56 mg, 96%) as colorless crystals with m.p. 64—65 °C
0
(
cf. Ref. 12: m.p. 54—55.5 °C), [α]D2 +119 (c 0.05; CH Cl ).
2
2
2
,4
Found (%): C, 56.18; H, 6.50. C H O . Calculated (%): C, 56.25;
6
8
3
+
+
H, 6.29. MS, m/z (Irel (%)): 128 [M] (1), 110 [M – H O]
2.5), 97 (77), 69 (16), 53 (29), 41 (100). H NMR (CDCl ), δ:
.89 (ddd, 1 H, synꢀH(6), J = 4.9 Hz, J = 3.5 Hz and 4.2 Hz);
.27 (ddd, 1 H, antiꢀH(6), J = 4.9 Hz, J = 8.0 Hz, J = 8.5 Hz);
.11 (dddd, 1 H, H(5), J5 = 8.5 Hz and 3.5 Hz, J = 5.7 Hz,
J4,5 = 1.0 Hz); 2.18 (ddd, 1 H, H(1), J5,6 = 8.0 Hz and 4.2 Hz,
3J1 = 5.7 Hz); 3.21 (br.s, 1 H, OH); 3.74 and 3.85 (both dd, 1 H
2
1
(
0
1
2
3
3
2
3
2
3
3
was subjected to column chromatography on SiO (benzene—
2
3
3
AcOEt, 1 : 1) to obtain acetates 14 (0.98 g, ∼ 90%) as colorless oil
,6
1,5
3
1
containing ( H NMR data) a mixture of (1S,2S,4S,5S,6R)ꢀ and
(1S,2S,4R,5S,6R)ꢀisomers in the ratio ∼ 5 : 1. (1S,2S,4S,5S,6R)ꢀ
,5
2
3
1
2
each, CH , J = 12.3 Hz, J = 4.5 Hz and 3.6 Hz); 4.42 (dd, 1 H,
H(4), 3J = 3.6 Hz and 4.5 Hz). C NMR (CDCl ), δ: 11.7
Isomer: H NMR (CDCl ) δ: 0.62 (ddd, 1 H, synꢀH(7), J = 4.9 Hz,
2
3
13
3
2
J = 5.0 Hz and 5.1 Hz); 0.90 (ddd, 1 H, antiꢀH(7), J = 4.9 Hz,
J = 8.4 Hz, J = 8.7 Hz); 1.09 and 1.20 (both m, 1 H each, H(1)
3
3
3
(
C(6)), 17.9 and 19.7 (C(1) and C(5)), 64.6 (CH O), 81.4 (C(4)),
2
1
76.7 (C=O).
and H(6)); 2.07 and 2.10 (both s, 3 H each, 2 COMe); 3.29 (dd, 1 H,
3
B. Ketone 8 (0.20 g, 1.4 mmol) was added to a suspension of
H(5), J = 2.3 Hz and 3.6 Hz); 3.48 (s, 3 H, OMe); 3.93 (ddd, 1 H,
3
freshly prepared manganese dioxide (4.5 g) in 5% aq. H SO
H(2), J = 6.8 Hz, 4.4 Hz, and 4.0 Hz); 4.29 (dd, 1 H, H (8),
2
4
a
2
3
2
(
25 mL) with vigorous stirring and the mixture was stirred for
J = 11.5 Hz, J = 6.8 Hz); 4.32 (dd, 1 H, H (8), J = 11.5 Hz,
b
J = 4.4 Hz); 5.92 (br. d, 1 H, H(4), J = 3.6 Hz). C NMR
3
3
13
4
8 h at 20 °C. The major part of manganese dioxide was separatꢀ
ed by decantation, to decompose the rest of MnO , anhydrous
(CDCl ), δ: 9.2 (C(7)); 10.7 and 11.4 (C(1) and C(6)); 20.5 and
2
3
Na SO was added in portions to the suspension and the solution
20.7 (COMe); 56.9 (OMe); 65.8 (CH O); 70.4 (C(2)); 74.7
2
3
2
obtained was extracted with ethyl acetate (3×20 mL). The organꢀ
(C(5)); 91.5 (C(4)); 168.9 and 170.5 (COO). (1S,2S,4R,5S,6R)ꢀ
1
2
ic extracts were dried with anhydrous MgSO , passed through
Isomer: H NMR (CDCl ), δ: 0.37 (ddd, 1 H, synꢀH(7), J = 5.0
4
3
3
a short layer of SiO , the solvents were evaporated to obtain
Hz, J = 5.0 Hz and 5.1 Hz); 1.04 (m, 1 H, H (7)); 1.17 and 1.27
2
b
1
13
a substance (0.16 g, 85%) as colorless oil, whose H and C NMR
spectra were identical to those of lactone 12 obtained by method
A (the purity was ~96%).
(both m, 1 H each, H(1) and H(6)); 2.09 and 2.12 (both s, 3 H
3
each, 2 COMe); 3.18 (dd, 1 H, H(5), J = 2.5 Hz and 4.6 Hz);
3.49 (s, 3 H, OMe); 3.76 (m, 1 H, H(2)); 4.24 (m, 2 H, CH O);
2
C. (1S,2S,4R,6R)ꢀ7,9ꢀDioxatricyclo[4.2.1.02,4]nonanꢀ5ꢀol
6.01 (br. d, 1 H, H(4), J = 2.5 Hz). C NMR (CDCl ), δ: 9.5
3
13
3
(
10) (0.10 g, 0.7 mmol) was added in one portion to a solution of
(C(7)), 10.8 and 11.6 (C(1) and C(6)), 18.7 and 24.5 (COMe),
KMnO4 (0.22 g, 1.4 mmol) in 5% aq. H SO (25 mL) with
57.1 (OMe), 64.0 (CH O), 66.9 (C(2)), 76.2 (C(5)), 83.4 (C(4)),
2
4
2
stirring and the reaction mixture was stirred for 1 h at 20 °C.
A precipitate of manganese dioxide formed was dissolved by
in portion addition of anhydrous Na SO until the solution beꢀ
169.5 and 172.5 (COO).
Reaction of ketone 15 with mꢀchloroperoxybenzoic acid. A.
mꢀChloroperoxybenzoic acid (0.61 g, 3.9 mmol) was added to
a solution of ketone 15 (0.50 g, 3 mmol) in CH Cl (15 mL) with
2
3
came colorless. The reaction mixture was extracted with AcOEt
3×15 mL) and the organic extracts were dried with anhydrous
2
2
(
stirring and the mixture was stirred for 5 h at 25 °C. The reaction

Oxidation of levoglucosenone derivatives
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
1935
mixture was treated with saturated aq. NaHCO until the gas
extracts were dried with anhydrous MgSO . After the solvent
3
4
evolution ceased, the organic layer was separated, the aqueous
was evaporated, the target product was isolated by preparative
layer was extracted with CH Cl (3×15 mL), and the combined
TLC on SiO (benzene—AcOEt, 1 : 1, R 0.65) to obtain lactone
2
2
2
f
organic extracts were dried with anhydrous MgSO . The solvent
20 (70 mg, 72%), identical to that obtained earlier.
4
was evaporated in vacuo and the residue was recrystallized from
benzene to obtain colorless crystals (0.50 g, ∼ 90%) containing
(1S,2S,4R,5R,6R)ꢀ and (1S,2S,4R,5S,6R)ꢀ3ꢀ(7,9ꢀDioxaꢀ
2
,4
tricyclo[4.2.1.0 ]nonanꢀ5ꢀyl)propionic acids (21). Cyclobutanꢀ
one 16 (54 mg, 0.3 mmol) was added to a 10% aq. H SO (4 mL)
1
13
compounds 18 and 19 ( H and C NMR data) in the molar ratio
10 : 1. (1R,4S,5R)ꢀ2´ꢀOxospiro{6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀ
2
4
∼
at 50 °C, the mixture was stirred for 10 min, cooled to room
temperature, and extracted with EtOAc (3×10 mL). The organꢀ
1
eneꢀ4,5´ꢀoxolane} (18). H NMR (CDCl ), δ: 2.10 (ddd, 1 H,
H (4´), J = 13.5 Hz, J = 9.0 Hz and 9.5 Hz); 2.41 (ddd, 1 H,
H (4´), J = 13.5 Hz, J = 6.6 Hz and 7.8 Hz); 2.59 (m, 2 H,
H C(3´)); 3.82 (dd, 1 H, exoꢀH(7), J = 6.8 Hz, J = 4.1 Hz);
3
2
3
ic extracts were dried with anhydrous MgSO and the solvent
a
4
2
3
was evaporated in vacuo to obtain a mixture of two stereoisomerꢀ
ic acids (1S,2S,4R,5R,6R)ꢀ21 and (1S,2S,4R,5S,6R)ꢀ21 (44 mg,
b
2
3
2
2
1
13
3
3
.94 (d, 1 H, endoꢀH(7), J = 6.8 Hz); 4.73 (dd, 1 H, H(1),
J = 4.1 Hz and 4.2 Hz); 5.33 (d, 1 H, H(5), J3 = 2.4 Hz); 5.64
dd, 1 H, H(3), J = 10.1 Hz, J = 2.4 Hz); 6.21 (dd, 1 H, H(2),
J = 10.1 Hz, J = 4.2 Hz). C NMR (CDCl ), δ: 27.1 (C(4´)),
74%) (colorless oil) in the ratio ∼ 4.2 : 1 ( H and C NMR data).
Found (%): C, 60.34; H, 7.27. C H O . Calculated (%):
,5
10 14
4
3
+
(
3
C, 60.59; H, 7.12. MS, m/z (I (%)): 198 [M] (2), 180
[M – H O] (10), 152 (15), 92 (82), 83 (95), 79 (63), 55 (25).
(1S,2S,4R,5R,6R)ꢀIsomer. H NMR (CDCl ), δ: 0.46 (ddd, 1 H,
antiꢀH(3), J = 4.8 Hz, J = 8.2 Hz and 8.9 Hz); 0.56 (ddd, 1 H,
3
,5
rel
3
13
+
3
2
1
3
1
0.6 (C(3´)), 70.5 (C(7)), 71.5 (C(1)), 84.8 (C(4)), 102.0 (C(5)),
3
2
3
28.1 (C(3)), 131.6 (C(2)), 175.9 (C=O).
B. Colorless crystals (0.36 g, 93%) containing ( H and
1
2
3
synꢀH(3), J = 4.8 Hz, J = 5.0 Hz and 5.4 Hz); 0.91 (m, 1 H,
13
C NMR data) compounds 18 and 19 in the molar ratio ∼ 1 : 3
H(4)); 1.01 (m, 1 H, H(2)); 1.56—1.70 (m, 2 H, CH (β)); 1.92
2
3
were obtained similarly from ketone 15 (0.33 g, 2 mmol) and
MCPBA (1.03 g, 6 mmol) after stirring for 5 days and recrystalliꢀ
zation from benzene. (1R,2S,4S,5S,6R)ꢀ2´ꢀOxospiro{3,7,9ꢀ
(ddd, 1 H, H(5), J4 = 5.4 Hz, J = 8.0 Hz and 11.1 Hz); 2.42
(ddd, H , CH (α), J = 16.3 Hz, J = 7.4 Hz and 8.8 Hz); 2.53
(ddd, H , CH (α), J = 16.3 Hz, J = 6.0 Hz and 8.8 Hz); 3.76
(dd, 1 H, exoꢀH(8), J = 6.7 Hz, J = 4.4 Hz); 3.96 (d, 1 H,
,5
2
3
a
2
2
3
b
2
trioxatricyclo[4.2.12 ]nonaneꢀ5,5´ꢀoxolane} (19). H NMR
,4
1
2
3
2
3
(
3
CDCl ), δ: 2.21 (m, 1 H, CH CH ); 2.63 (m, 3 H, CH CH );
endoꢀH(8), J = 6.7 Hz); 4.54 (br. d, 1 H, H(1), J = 4.4 Hz);
3
2
2
2
2
3
13
.15 (dd, 1 H, H(4), J = 3.9 Hz, J = 2.5 Hz); 3.28 (dd, 1 H,
5.00 (br.s, 1 H, H(6)); 9.2—10.5 (br.s, 1 H, OH). C NMR
4
,6
3
2
H(2), J = 3.9 Hz and 1.5 Hz); 3.92 (dd, 1 H, exoꢀH(8), J = 7.7 Hz,
3
(CDCl ), δ: 4.1 (C(3)); 8.1 (C(2)); 14.7 (C(4)); 25.9 ((CH (β));
3
2
2
J = 4.2 Hz); 4.18 (d, 1 H, endoꢀH(8), J = 7.7 Hz); 4.78 (br. dd,
31.7 (CH (α)); 37.5 (C(5)); 69.4 (C(8)); 71.0 (C(1)); 103.6
2
3
1
1
H, H(1), J = 4.2 Hz and 1.5 Hz); 5.03 (d, 1 H, H(6),
(C(6)); 179.4 (COOH). (1S,2S,4R,5S,6R)ꢀIsomer. H NMR
(CDCl ), δ: 0.52 (ddd, synꢀH(3), J = 4.6 Hz, J = 5.0 Hz and
5.1 Hz); (ddd, antiꢀH(3), J = 4.6 Hz, J = 8.4 Hz and 8.7 Hz);
3.78 (br. dd, exoꢀH(8), J = 6.5 Hz, J = 4.2 Hz); 3.93 (br. d,
J4,6 = 2.5 Hz). 13C NMR (CDCl ), δ: 26.5 and 27.2 (C(3´) and
2
3
3
3
2
3
C(4´)), 50.4 (C(2)), 52.0 (C(4)), 67.8 (C(8)), 70.2 (C(1)), 79.7
2
3
(
C(5)), 100.9 (C(6)), 180.2 (C=O).
1S,2S,4R,5S,6R)ꢀ2´ꢀOxospiro{7,9ꢀdioxatricyclo[4.2.1.02,4]ꢀ
endoꢀH(8), J = 6.5 Hz); 4.57 (br. d, H(1), J = 4.2 Hz); 5.15
2
3
(
nonaneꢀ5,5´ꢀoxolane} (20). A. A mixture of (1S,2S,4R,5S,6R)ꢀ
(m, H(6)), the rest of the signals overlap with signals for the
spiro{7,9ꢀdioxatricyclo[4.2.1.02 ]nonaneꢀ5,2´ꢀcyclobutanone}
,4
major isomer. C NMR (CDCl ), δ: 9.2 (C(3)), 9.4 (C(2)), 15.0
13
3
(
16) (108 mg, 0.6 mmol) and MCPBA (155 mg, 0.9 mmol) in
(C(4)), 26.8 (CH (β)), 31.3 (CH (α)), 39.9 (C(5)), 70.4 (C(8)),
2
2
CH Cl (10 mL) was stirred for 10 h and then neutralized with
70.5 (C(1)), 101.6 (C(6)), 179.2 (COOH).
2
2
saturated aq. NaHCO until the gas evolution ceased. The orꢀ
ganic layer was separated, the aqueous layer was extracted with
(1S,4S,5R)ꢀ2´ꢀOxospiro{6,8ꢀdioxabicyclo[3.2.1]octaneꢀ4,5´ꢀ
oxolane} (22). A. A mixture of (1S,4S,5R)ꢀspiro{6,8ꢀdioxaꢀ
bicyclo[3.2.1]octaneꢀ4,2´ꢀcyclobutanone} (17) (84 mg, 0.5 mmol)
and MCPBA (125 mg, 0.7 mmol) in CH Cl (8 mL) was stirred
3
CH Cl (3×10 mL), the combined organic extracts were dried
2
2
with anhydrous MgSO and the solvent was evaporated in vacuo
4
2
2
to obtain lactone 20 (106 mg, 90%) as colorless crystals, m.p.
for 10 h and neutralized with saturated aq. NaHCO until the gas
3
9
3—94 °C. Found (%): C, 61.04; H, 6.31. C H O . Calculated
evolution ceased. The organic layer was separated, the aqueous
10
12
4
+
(
%): C, 61.22; H, 6.17. MS, m/z (Irel (%)): 150 [M – HCO H]
layer was extracted with CH Cl (3×10 mL), the combined orꢀ
2
2
2
(
100), 137 (7), 122 (15), 95 (70), 81 (65), 67 (50), 55 (85).
ganic extracts were dried with anhydrous MgSO and the solvent
4
1
H NMR (CDCl ), δ: 0.74 (m, 1 H, antiꢀH(3)); 1.08 (m, 3 H,
was evaporated in vacuo to obtain lactone (1S,4S,5R)ꢀ22 (85
mg, 92%) as colorless crystals, m.p. 134—135 °C. Found (%):
C, 58.58; H, 6.74. C H O . Calculated (%): C, 58.69; H, 6.57.
3
2
H(2), synꢀH(3), H(4)); 2.10 (ddd, 1 H, H (4´), J = 13.5 Hz,
a
3
3
3
3
3
3
2
J = 9.8 Hz, J = 4.5 Hz); 2.34 (ddd, 1 H, H (4´), J = 13.5 Hz,
b
9
12
4
3
2
1
J = 10.1 Hz, J = 8.5 Hz); 2.54 (ddd, 1 H, H (3´), J = 17.6 Hz,
H NMR (CDCl ), δ: 1.53 (m, 1 H, endoꢀH(2)); 1.80—1.98
3
a
3
2
J = 8.5 Hz, J = 4.5 Hz); 2.67 (ddd, 1 H, H (3´), J = 17.6 Hz,
(m, 3 H, H C(3), H C(4´)); 2.12—2.29 (m, 2 H, exoꢀH(2),
b
2 a
3
2
2
J = 10.1 Hz, J = 9.8 Hz); 3.79 (dd, 1 H, exoꢀH(8), J = 6.8 Hz,
J = 4.6 Hz); 3.92 (d, 1 H, endoꢀH(8), J = 6.8 Hz); 4.69 (br. d,
H, H(1), J = 4.1 Hz); 4.97 (s, 1 H, H(6)). C NMR (CDCl ),
H C(4´)); 2.56 (m, 2 H, H C(3´)); 3.82 (ddd, exoꢀH(7), J =
b 2
= 7.0 Hz, J = 4.9 Hz, J = 1.6 Hz); 3.89 (br. d, 1 H, endoꢀH(7),
J = 7.6 Hz); 4.59 (m, 1 H, H(1)); 5.12 (br.s, 1 H, H(5)).
2
3
3
13
2
1
3
13
δ: 6.5 (C(3)), 13.8 (C(2)), 15.1 (C(4)), 28.1 (C(4´)), 31.3 (C(3´)),
C NMR (CDCl ), δ: 25.9 (C(2)); 27.8 (C(3´)); 28.2 (C(3));
3
6
9.6 (C(8)), 70.4 (C(1)), 83.2 (C(5)), 102.3 (C(6)), 176.4 (C=O).
B. Cyclobutanone 16 (90 mg, 0.5 mmol) was added to
30.0 (C(4´)); 67.2 (C(7)); 72.6 (C(1)); 82.6 (C(4)); 101.7 (C(5));
176.0 (C=O).
a solution of KMnO (60 mg, 0.38 mmol) in 5% aq. H SO (8 mL)
B. Cyclobutanone 17 (101 mg, 0.6 mmol) was added to
a solution of KMnO (67 mg, 0.42 mmol) in 5% aq. H SO (5 mL)
4
2
4
and the reaction mixture was stirred for 6—7 min at 20 °C until
the solution turned colorless. A precipitate of manganese diꢀ
oxide formed was dissolved by addition in portions of anhydrous
Na SO , the mixture was extracted with AcOEt (3×15 mL), the
4
2
4
and the reaction mixture was heated for 6—7 min at 40 °C.
A precipitate of manganese dioxide was dissolved by addition in
portions of anhydrous Na SO , the mixture was extracted with
2
3
2
3

1
936
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 10, October, 2010
Novikov et al.
AcOEt (3×15 mL), the extracts were dried with anhydrous
2. K. Koseki, T. Ebata, H. Kawakami, H. Matasushita, Y. Naoi,
K. Itoh, Heterocycles, 1990, 31, 423.
MgSO . The solvent was evaporated in vacuo and the residue
4
was recrystallized from the hexane—benzene (2.5 : 1) solvent
mixture to obtain stereoisomeric lactones (1S,4S,5R)ꢀ22 and
3. Eur. Pat. 411403; Chem Abstr., 1991, 114, 185135m.
4. H. Kawakami, T. Ebata, K. Koseki, K. Matsumoto, H. Mataꢀ
sushita, Y. Naoi, K. Itoh, Heterocycles, 1990, 31, 2041.
5. T. Ebata, K. Matsumoto, H. Yoshikoshi, K. Koseki, H. Kaꢀ
wakami, H. Matasushita, Heterocycles, 1990, 31, 1585.
6. K. Matsumoto, T. Ebata, K. Koseki, K. Okano, H. Kawaꢀ
kami, H. Matasushita, Bull. Chem. Soc. Jpn., 1995, 68, 670.
7. F. A. Valeev, I. N. Gaisina, M. S. Miftakhov, G. A. Tolsꢀ
tikov, Zh. Org. Khim., 1993, 29, 105 [Russ. J. Org. Chem.
(Engl. Transl.), 1993, 29].
(
1S,4R,5R)ꢀ22 (the ratio ∼ 3 : 1) (88 mg, 80%) as colorless crysꢀ
1
13
tals. The H and C NMR spectra of the major isomer agrees
with those for (1S,4S,5R)ꢀisomer obtained by method A.
1
(
3
(
1S,4R,5R)ꢀIsomer. H NMR (CDCl ), δ: 1.69 (m, endoꢀH(2));
3
2
3
.86 (ddd, exoꢀH(7), J = 7.1 Hz, J = 5.0 Hz, J = 1.6 Hz); 3.96
br.d, endoꢀH(7), 2J = 7.1 Hz); 4.53 (m, H(1)); 5.14 (br.s,
H(5)), the rest of the signals overlap with signals for the major
13
isomer. C NMR (CDCl ), δ: 26.9 and 27.1 (C(2) and C(3´));
3
2
(
7.9 and 28.3 (C(3) and C(4´)); 68.0 (C(7)); 72.8 (C(1)); 84.5
C(4)); 103.4 (C(5)); 175.9 (C=O).
1S,4R,5R)ꢀ and (1S,4S,5R)ꢀ3ꢀ(6,8ꢀDioxabicyclo[3.2.1]octꢀ
ꢀyl)propionic acids (23). A solution of spiro{6,8ꢀdioxabicycloꢀ
8. F. A. Valeev, I. N. Gaisina, M. S. Miftakhov, Zh. Org. Khim.,
1996, 32, 1365 [Russ. J. Org. Chem. (Engl. Transl.), 1996,
32, 1319].
9. A. V. Samet, D. N. Lutov, L. D. Konyushkin, Yu. A. Strelenꢀ
ko, V. V. Semenov, Tetrahedron: Asymmetry, 2008, 19, 691.
10. A. V. Samet, A. M. Shestopalov, D. N. Lutov, L. A. Rodiꢀ
novskaya, L. A. Shestopalov, V. V. Semenov, Tetrahedron:
Asymmetry, 2007, 18, 1986.
(
4
[
1
3.2.1]octaneꢀ4,2´ꢀcyclobutanone} (17) (50 mg, 0.3 mmol) in
5% aq. H SO (5 mL) was heated for 10 min at 90 °C. The
2
4
solution was cooled to room temperature, extracted with EtOAc
3×10 mL), dried with anhydrous MgSO , and the solvent was
(
4
evaporated in vacuo to obtain a mixture of two stereoisomeric
acids (1S,4R,5R)ꢀ23 and (1S,4S,5R)ꢀ23 (41 mg, 73%) (yellowꢀ
ish oil) in the ratio ∼ 3 : 1 ( H and C NMR data). Found (%):
11. R. A. Novikov, R. R. Rafikov, E. V. Shulishov, L. D. Konyꢀ
ushkin, V. V. Semenov, Yu. V. Tomilov, Izv. Akad. Nauk,
Ser. Khim., 2009, 325 [Russ. Chem. Bull., Int. Ed., 2009,
58, 327].
12. M. MartinꢀVila, N. Hanafi, J. M. Jimenez, A. AlvarezꢀLareꢀ
na, J. F. Piniella, V. Branchadell, A. Oliva, R. M. Ortuno,
J. Org. Chem., 1998, 63, 3581.
1
13
C, 57.87; H, 7.71. C H O . Calculated (%): C, 58.05; H, 7.58.
9
14
4
1
(
1S,4R,5R)ꢀIsomer. H NMR (CDCl ), δ: 1.32—1.56 (m, 3 H,
3
endoꢀH(2), endoꢀH(3), H , CH (β)); 1.62—1.78 (m, 3 H,
a
2
exoꢀH(2), exoꢀH(3), H , CH (β)); 1.87 (m, 1 H, H(4)); 2.36
b
2
2
3
(
m, 2 H, (CH (α)); 3.77 (ddd, exoꢀH(7), J = 7.1 Hz, J = 4.9 Hz,
J = 1.6 Hz); 3.84 (dd, 1 H, endoꢀH(7), J = 7.1 Hz, J = 1.1 Hz);
13. Y. Zhao, T. Yang, M. Lee, D. Lee, M. G. Newton, C. K.
Chu, J. Org. Chem., 1995, 60, 5236.
2
2
4
.51 (m, 1 H, H(1)); 5.29 (br.s, 1 H, H(5)); 9.20 (br.s, 1 H, OH).
14. R. R. Rafikov, R. A. Novikov, E. V. Shulishov, L. D. Konyꢀ
ushkin, V. V. Semenov, Yu. V. Tomilov, Izv. Akad. Nauk,
Ser. Khim., 2009, 1866 [Russ. Chem. Bull., Int. Ed., 2009,
58, 1927].
13
C NMR (CDCl ), δ: 22.3 (CH (β)); 27.0 and 28.5 (C(2) and
3
2
C(3)); 31.0 (CH (α)); 40.1 (C(4)); 68.3 (C(7)); 73.4 (C(1)); 103.9
2
1
(
C(5)); 179.2 (COOH). (1S,4S,5R)ꢀIsomer. H NMR (CDCl ),
3
δ: 1.95—2.01 (m, exoꢀH(2), exoꢀH(3)); 3.74 (m, exoꢀH(7)); 3.92
15. R. R. Rafikov, R. A. Novikov, E. V. Shulishov, Yu. V. Tomꢀ
ilov, Izv. Akad. Nauk, Ser. Khim., 2009, 2371 [Russ. Chem.
Bull., Int. Ed., 2009, 58, 2449].
16. G. R. Krow, Organic Reactions, John Wiley and Sons, New
York, 1993, 43, p. 251.
2
(
dd, 1 H, endoꢀH(7), J = 7.1 Hz, J = 1.0 Hz); 4.48 (m, 1 H,
H(1)); 5.33 (m, 1 H, H(5)), the rest of the signals overlap with
the signals for the major isomer. 13C NMR (CDCl ), δ: 19.5
3
(
(
CH (β)); 24.8 and 25.5 (C(2) and C(3)); 32.3 (CH (α)); 38.7
2 2
C(4)); 67.4 (C(7)); 73.9 (C(1)); 104.1 (C(5)); 179.2 (COOH).
17. L. M. Mikkelsen, S. L. Krintel, J. JiménezꢀBarbero, T. Skryꢀ
dstrup, J. Org. Chem., 2002, 67, 6297.
The authors are grateful to Yu. A. Strelenko (IOCh
18. M. E. Jung, M. Kiankarimi, J. Org. Chem., 1998, 63, 8133.
19. J. Attenburrow, A. F. B. Cameron, J. H. Chapman, R. M.
Evans, B. A. Hems, A. B. A. Jansen, T. Walker, J. Chem.
Soc., 1952, 1094.
RAS) for the methodical help in recording twoꢀdimenꢀ
1
13
sional H and C NMR spectra on a Bruker DRXꢀ500
spectrometer.
This work was financially supported by the Ministry of
Education and Science of the Russian Federation (State
Contract No. 02.740.11.0258).
References
1
. M. S. Miftakhov, F. A. Valeev, I. N. Gaisina, Usp. Khim.,
993, 62, 922 [Russ. Chem. Rev. (Engl. Transl.), 1993, 62].
Received March 24, 2010;
in revised form September 17, 2010
1