Reactions of levoglucosenone and its derivatives with diazo compounds

Article abstract of DOI:10.1007/s11172-010-0011-9

The reaction of levoglucosenone with methyl diazoacetate gives first 1-pyrazoline, which then, depending on the reaction conditions, either undergoes denitrogenation to form a mixture of cyclopropane and unsaturated compounds, or isomerizes into 2-pyrazoline capable of easy cyclodimerizing in the presence of pyridine through the addition of the N-H fragments to the carbonyl groups. The product of levoglucosenone reduction, 6,8-dioxabicyclo [3.2.1]oct-2-en-4-ol, affords the corresponding cyclopropane upon the action of diazomethane in the presence of a Pd catalyst, whereas its reaction with methyl diazoacetate in the presence of Rh₂(OAc)₄ leads to the insertion of methoxycarbonyl carbene into the OH bond. From the ester obtained, l-diazo-3-6,8-dioxabicyclo[3.2.1]oct-2-en-4-yloxypropan-2-one was synthesized in several steps, its denitrogenation under the action of copper compounds is accompanied by the intramolecular insertion of the carbene into the C(4)-H bond of the levoglucosenone fragment to yield the corresponding spirane.

Full text of DOI:10.1007/s11172-010-0011-9

Russian Chemical Bulletin, International Edition, Vol. 58, No. 2, pp. 327—334, February, 2009
327
Reactions of levoglucosenone and its derivatives
with diazo compounds*
R. A. Novikov, R. R. Rafikov, E. V. Shulishov, L. D. Konyushkin, V. V. Semenov, and Yu. V. Tomilov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6390. Eꢀmail: tom@ioc.ac.ru
The reaction of levoglucosenone with methyl diazoacetate gives first 1ꢀpyrazoline, which
then, depending on the reaction conditions, either undergoes denitrogenation to form a mixture
of cyclopropane and unsaturated compounds, or isomerizes into 2ꢀpyrazoline capable of easy
cyclodimerizing in the presence of pyridine through the addition of the N—H fragments to the
carbonyl groups. The product of levoglucosenone reduction, 6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀenꢀ
4ꢀol, affords the corresponding cyclopropane upon the action of diazomethane in the presence
of a Pd catalyst, whereas its reaction with methyl diazoacetate in the presence of Rh2(OAc)4
leads to the insertion of methoxycarbonyl carbene into the OH bond. From the ester obtained,
1ꢀdiazoꢀ3ꢀ{6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀenꢀ4ꢀyloxy}propanꢀ2ꢀone was synthesized in several
steps, its denitrogenation under the action of copper compounds is accompanied by the
intramolecular insertion of the carbene into the C(4)—H bond of the levoglucosenone fragꢀ
ment to yield the corresponding spirane.
Key words: levoglucosenone, pyrazolines, diazomethane, methyl diazoacetate, cycloꢀ
propanation, insertion, NMR spectra.
6,8ꢀDioxabicyclo[3.2.1]octane derivatives possess a
wide range of biological activity,1,2 while optically active
compounds of this series can be used as substrates in
various enantioselective reactions.
In continuation of our studies in the field of chemistry
of diazo compounds and in order to synthesize new optiꢀ
cally active derivatives of 6,8ꢀdioxabicyclo[3.2.1]octane
including those with cyclopropane fragments, we syntheꢀ
sized derivatives of easily available carbohydrate enone,
viz., levoglucosenone (1), which can be obtained from
cellulose of any origin by acid hydrolysis at 250—300 °C
(see Refs 3 and 4).
Such chemical transformations of levoglucosenone
and its derivatives as reactions with diazo compounds and
synthesis of cyclopropane compounds based on them are
virtually not investigated. In the literature, there are few
works devoted to the study of reactions of diazo comꢀ
pounds with levoglucosenone or its derivatives, which
can to a certain extent result from specific properties of
this unsaturated ketone. Thus direct cyclopropanation
of levoglucosenone by decomposition of diazomethane or
methyl diazoacetate (MDA) in the presence of catalysts
gives no cyclopropanation products because of lowered
electron density on the double bond.5 Though, 1,3ꢀdipoꢀ
lar cycloaddition of diazomethane to the levoglucosenone
C=C bond leads to the formation of 1ꢀpyrazoline,5 howꢀ
ever, there are no data on possibility of its denitrogenation
into the corresponding cyclopropane. The reaction of
levoglucosenone with MDA in refluxing benzene (48 h)
afforded two stereoisomeric hexacyclic adducts containing
two levoglucosenone molecules per molecule of MDA as
the isolated reaction products.5 Presumably, after mixing
of the reactants, 1ꢀpyrazoline 2 is formed first followed
by its easy isomerization to 2ꢀpyrazoline 3. Its Michael
addition to the second molecule of levoglucosenone is
followed by the intramolecular cyclization through
the reaction of the active methylene fragment with the
carbonyl group. It is of note that the reaction of sulfur
ylides with the enone fragment of levoglucosenone proꢀ
ceeds also in different ways. Thus the reaction with
Me2S=CH2 involves the carbonyl group and is accompaꢀ
nied by the formation of an unsaturated oxirane,6 whereas
acyl ylides add to the C=C bond and give cyclopropanated
ketones.7,8
Cyclopropane derivatives were also obtained by the
reaction of 3ꢀiodoꢀ6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀenꢀ
4ꢀone9 with ethyl cyanoacetate or diethyl malonate in the
presence of a strong base; the yields of cyclopropane
derivatives of levoglucosenone were 70—80% (see Refs 10
and 11).
* On the occasion of the 75th anniversary of the foundation
of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 325—332, February, 2009.
1066ꢀ5285/09/5802ꢀ0327 © 2009 Springer Science+Business Media, Inc.

328
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Novikov et al.
Results and Discussion
and MDA in CH2Cl2 and the mixture is kept for 2 days at
∼20 °C. After the solvent and excess MDA were evaporated,
a crystalline product was obtained, in which the ratio of the
MDA and levoglucosenone fragments is 1 : 1. The 1H and
13C NMR spectra of this compound exhibit a double set
of signals for these fragments (see Experimental); in the
13C NMR spectrum, there are no lowꢀfield signals in
the region of carbonyl group, while two signals of C atoms
bearing no hydrogen atoms appear instead at δ ∼100. All
the spectral data indicate that the compound obtained has
the heptacyclic structure 4 (Scheme 2) resulting from the
dimerization of pyrazoline 3 through the double nucleoꢀ
philic attack by the nitrogen atoms on two keto groups.
These transformations result in a new sixꢀmembered
heterocycle with conversion of the carbonyl groups to
hydroxy groups. Different stereoisomers can be formed,
however, compound 4 was obtained as a single isomer,
which follows from the chromatographic homogeneity
As was mentioned above, pyrazoline 3 formed in the
reaction of levoglucosenone (1) with MDA cannot be
isolated because of its reaction with the second molecule
of 1. To avoid (or, at least, considerably reduce) the aldol
condensation of 3 with the starting levoglucosenone,5 we
studied the reaction of levoglucosenone with a 1.5—2ꢀfold
molar excess of MDA, the reaction being monitored by
1H NMR spectroscopy. In a mixture of 1 and MDA kept
in CH2Cl2 at ∼20 °C for 1 h, two new sets of signals in the
spectrum appear that belong to pyrazolines 2 and 3 in
the ratio ∼2 : 1. The conversion of levoglucosenone at this
moment is ∼30%. After 3.5 h, the conversion of 1 rises to
50—55% and the ratio of pyrazolines 2 and 3 changes
to ∼1 : 1 (Scheme 1). After 1 day, pyrazoline 3 is formed
predominantly, however, this is accompanied by the
appearance of “extra” signals in the spectrum. Pyrazoline
3 was isolated in ∼58% yield using preparative TLC on
SiO2. The C(2)H and C(6)H methine protons are found
1
and the fact that the H and 13C NMR spectra of the
products obtained after several crystallizations were idenꢀ
tical. It thus follows that the addition of MDA to the
double bond of 1 is highly selective and, as in the case of
diazomethane,5 the adduct with exoꢀorientation of the
pyrazoline fragment is formed. This is inferred from
the low spinꢀspin coupling constant (J ≤ 1 Hz) of the
vicinal bridgehead protons H(6), H(7) and H(15), H(16).
The dimerization of pyrazoline 3 occurs also with high
selectivity so that one of the arising OH groups is directed
toward the anhydro bridge C(3)—O—C(5) and the other
is directed toward the oxygen bridge C(12)—O—C(15) of
the sixꢀmembered ring. This is the reason for the double
1
at δ 3.71 and 4.50 in the H NMR spectrum with vicinal
spinꢀspin coupling constant J2,6 equal to 11.2 Hz. It should
be noted that the signal for the proton at the angular C(1)
atom is shifted downfield as compared to the signal for
the H(8) atom, which is apparently due to its deshielding
by the ester substituent located in close proximity. In the
1H NMR spectrum of pyrazoline 2, the H(3) and H(6)
atoms resonate at δ 5.35 and 5.86 and the vicinal spinꢀ
spin coupling constants J2,3 and J2,6 with the proton H(2)
at δ 2.73 are equal to 9.0 and 9.8 Hz, respectively.
1
set of signals in the H and 13C NMR spectra; the signals
Scheme 1
for the protons of the hydroxy groups in CDCl3 resonate
at δ 5.10 and 7.65.
Scheme 2
When the reaction mixture was kept for longer time (for
example, for 4 days), a decrease in intensity of the signals for
pyrazoline 3 in the 1H NMR spectrum and appearance of a
double set of new signals of equal intensities was observed.
It turned out that the compound with this set of signals is
formed selectively and in high yield if 15—20 mol.% of
pyridine is initially added to a mixture of levoglucosenone
The nonequivalent spatial surroundings of the hydroxy
groups is also confirmed by the results of acylation of
compound 4. Thus its treatment with a threefold molar
excess of acetyl chloride in the presence of pyridine leads
to the acetylation of only one hydroxy group to yield
acetate 5, in which it is the sterically hindered OH group

Reactions of levoglucosenone with diazo compounds Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
329
oriented toward the oxygen bridge that apparently remains
unaffected. This is confirmed by a downfield shift of the
proton at the C(20) atom in the H NMR spectrum of
1H and 13C NMR spectra of compound 7, instead of sigꢀ
nals for the cyclopropane ring, exhibit signals characterisꢀ
tic of the CH2—C=CH fragment, in which the protons of
the methylene fragment are nonequivalent and resonate
as two signals with the geminal spinꢀspin coupling conꢀ
stant of 16.3 Hz.
Since direct cyclopropanation of levoglucosenone
by the catalytic decomposition of diazo compounds
cannot be accomplished, we have reduced enone 1
to 6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀenꢀ4ꢀol (8) following a
known scheme13,14 and studied its reactions with diazoꢀ
methane and methyl diazoacetate.
The addition of an ethereal solution of diazomethane
(or passing of CH2N2 in a flow of nitrogen) to a solution
of unsaturated alcohol 8 in CH2Cl2 containing a Pd(OAc)2
or Pd(acac)2 catalyst (0.5 mol.%) leads to 7,9ꢀdioxaꢀ
tricyclo[3.2.1.02,4]nonanꢀ5ꢀol (9) in high yield, in which
the cyclopropane fragment is exclusively oriented toward
the oxygen bridge.8 The oxidation of this product with
manganese dioxide affords the levoglucosenone cycloꢀ
propane derivative 10 in >90% yield (Scheme 4), which
cannot be obtained by direct cyclopropanation of enone 1
or thermal denitrogenation of its adduct with diazomethane.
1
acetate 5 by ∼1 ppm as compared to the starting diol 4,
which results from its deshielding by the acetoxy substituꢀ
ent in the cisoid position to this proton. The EI mass
spectrum of acetate 5 exhibits two fragments with m/z 226
and 268 resulting from the cleavage of the N(1)—C(2)
and N(10)—C(11) bonds and differing only in the presꢀ
ence of OH and OCOMe substituents, respectively.
The reflux of a benzene solution of dimer 4 in the
presence of acetic acid as a catalyst leads to its monoꢀ
merization: after 1 h, the 1H NMR spectrum of the reacꢀ
tion mixture indicates that it contains dimer 4 and
pyrazoline 3 in the ratio ∼1 : 1.5.
The character of chemical transformations is considꢀ
erably different if levoglucosenone is added to a boiling
benzene solution of MDA. In this case, neither pyrazoline
3 or its dimer 4, nor a 2 : 1 adduct of levoglucosenone to
MDA described earlier,5 are virtually formed. Rather a
∼1.8 : 1 mixture of methyl 5ꢀoxoꢀ7,9ꢀdioxatricycloꢀ
[4.2.1.02,4]nonaneꢀ3ꢀcarboxylate (6) and 2ꢀ(methoxyꢀ
carbonylmethyl)ꢀ6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀenꢀ4ꢀone
(7), which is difficult to separate, was obtained in overall
75% yield (Scheme 3). Samples containing up to ~90% of
each isomer were obtained using preparative TLC on SiO2.
It should be noted that the formation of cyclopropanes
and substituted olefins is quite typical of thermal decomꢀ
position of 1ꢀpyrazolines12 and the presence of electronꢀ
withdrawing substituents in pyrazolines, as a rule, faciliꢀ
tates the process of denitrogenation. Apparently, in the
thermal version of the reaction of levoglucosenone with
MDA the initially forming 1ꢀpyrazoline 2 much faster
loses the nitrogen molecule giving compounds 6 and 7
than isomerizes to 2ꢀpyrazoline 3.
Scheme 4
Scheme 3
In contrast to diazomethane, the decomposition of
MDA in the presence of Pd(OAc)2 at 25 °C gives no reacꢀ
tion products with unsaturated alcohol 8, only the starting
alcohol, dimethyl fumarate, and dimethyl maleate were
found in the reaction mixture. When Rh2(OAc)4 is used
instead of the palladium catalyst, MDA readily reacts
with compound 8, however, the denitrogenation of MDA
is accompanied not by cyclopropanation of the double
bond, but by insertion of methoxycarbonylcarbene15,16a
into the О—H bond to form unsaturated ester 11a, the
yield of which reaches 86% (Scheme 5).
In the 1H NMR spectrum of compound 6, the signals
for the protons of the cyclopropane ring are found at
3
δ 2.04—2.54 and the spinꢀspin coupling constant J3,2
=
3J3,4 = 4.1 Hz corresponds to the transꢀprotons, which
indicates the antiꢀorientation of the methoxycarbonyl subꢀ
stituent; the spinꢀspin coupling constant J1,2, being near
3
We also obtained esters 11 alternatively, i.e., by the
reaction of alcohol 8 with methyl (or ethyl) bromoacetate
zero, indicates that the cyclopropane fragment is directed
toward the oxygen atom of the sixꢀmembered ring. The

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Novikov et al.
Scheme 5
constant values for the protons of the cyclopropane ring
3Jtrans ≈ 3J2,3 ≈ 3J3,4 ≈ 4.4 Hz.
On heating in aqueous ethanolic solution of KOH and
subsequent acidification to pH 2.5—3, esters 11a,b are
converted to 2ꢀ{6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀenꢀ4ꢀyloxy}ꢀ
acetic acid (14) in up to 95% yield. Acid 14 is not very
stable in air and changes with time from a light orange oil
to a dark viscous mass. Despite the fact that the majority
of levoglucosenone derivatives are sensitive to HCl, which
opens the dioxolane ring,14,17 we succeeded in the transꢀ
formation of acid 14 to acyl chloride 15 on treatment with
oxalyl chloride in the presence of a catalytic amount of
pyridine; oneꢀpot reaction with excess of an ethereal
solution of diazomethane and chromatography on silica
gel afforded diazoketone 16 in moderate yield with the
dioxabicyclo[3.2.1]octene fragment remaining intact
(Scheme 6).
Scheme 6
R = Me (a), Et (b)
in the presence of a strong nonnucleophilic base, in parꢀ
ticular, potassium tertꢀbutoxide in dimethoxyethane.
However, in this case the reaction is less efficient and
esters 11a,b are obtained in lower yields and purities, than
in the generation of methoxycarbonylcarbene.
1
The H and 13C NMR spectra of compounds 11a,b
clearly trace the structure of unsaturated alcohol 8 with
additional signals characteristic of the CH2CO2R fragment.
And the protons of the methylene group due to their
magnetic nonequivalence are found at δH 4.0—4.3 as two
doublets with the spinꢀspin coupling constant of 16.4 Hz.
With compound 11a as an example, we showed that
using a fivefold excess of MDA in the presence of
Rh2(OAc)4, cyclopropanation of the double bond can also
be accomplished to afford diester 12 in ∼42% yield (see
Scheme 5). In this case, despite the large excess of MDA,
the conversion of the starting compound 11a is only ∼50%.
Dimethyl fumarate and dimethyl maleate are formed
in the reaction, which makes the isolation of the target
product difficult. In contrast to MDA, diazomethane
easily cyclopropanates the double bond of 11a in the presꢀ
ence of a palladium catalyst, for example Pd(acac)2. The
yield of 7,9ꢀdioxatricyclo[4.2.1.02,4]nonane derivative 13
is no less than 95% (see Scheme 5) and the compound
obtained can virtually be distilled in vacuo entirely. Both
cyclopropanation reactions proceed stereospecifically and
produce only one isomer. As in the preceding cases, the
attack at the double bond occurs from the sterically less
hindered side, i.e., from the side of the oxygen atom of
Reagents and conditions: i. 1) KOH, EtOH/H2O, 2) HCl, H2O;
ii. (COCl)2, Et3N, C6H6/DME; iii. CH2N2, Et2O.
1
The H and 13C NMR spectra of compounds 14 and
16 with allowance for the change in the nature of the
functional groups very much resemble the corresponding
spectra of ester 11a. In diazoketone 16, the signals for the
CHN2 fragment are observed at δH 5.88 and δC 53.4,
whereas in the 14N NMR spectrum, two signals for the
nitrogen atoms of the diazo group are at δN –119 and –10.
Further, we have studied decomposition of diazoꢀ
ketone 16 in CH2Cl2 in the presence of various catalysts.
Dilute solutions were used to make intramolecular transꢀ
formations predominant over intermolecular processes. It
turned out that Rh2(OAc)4 in catalytic amounts does not
virtually decompose diazoketone 16 even in boiling
CH2Cl2. Dirhodium tetrakis(trifluoroacetate) proved to be
a more active catalyst, however, it brings about nonselecꢀ
tive decomposition of the diazoketone and a mixture of
nonidentified compounds was obtained.
the sixꢀmembered ring (3J2,4 = 9.1 Hz; J1,2 and J4,5 are
near zero) and in the case of compound 12, the methoxyꢀ
carbonyl group in the tricyclic fragment is in the antiꢀ
position, which is testified by the spinꢀspin coupling
3
3
For the directed decomposition of diazoketone 16,
copper compounds proved to be the most suitable catalysts.

Reactions of levoglucosenone with diazo compounds Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
331
(λ 589 nm, a 2.5ꢀcm cuvette). Thinꢀlayer chromatography was
performed on Silicagel 60 plates (Merck), visualization of
compounds was made by the iodine vapor. For preparative
separations, column or plate chromatography was used (silica
gel 60, 0.040—0.063 mm, Merck) with the ratio of comꢀ
pound : sorbent being equal to ∼1 : 100. Levoglucosenone3,4
(96% purity) and 6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀenꢀ4ꢀol (8)12,13
were synthesized according to the described procedures. Solvents
of chemically pure grade (>99.5%) were used in the work without
additional purification. Copper(I) chloride was precipitated from
its hydrochloric acid solution by dilution with distilled water,
filtered off under argon, sequentially washed with acetone and
CH2Cl2, and dried in a vacuum desiccator.
For instance, the reflux of diazoketone 16 in CH2Cl2 in
the presence of a freshly prepared cuprous chloride leads
to its denitrogenation and intramolecular insertion16b,18 of
a transient carbene into the C(4)—H bond to furnish
1´,6,8ꢀtrioxaspiro[bicyclo[3.2.1]octꢀ2ꢀenꢀ4,5´ꢀcyclopentanꢀ
3´ꢀone] (17) in up to 55% yield (Scheme 7). A similar
reaction takes place also in the presence of cupric acetylꢀ
acetonate, however, the process is less efficient, and
spirane 17 is obtained in this case in ≤40% yield.
Scheme 7
3ꢀMethoxycarbonylꢀ4,5ꢀdiazaꢀ9,11ꢀdioxatricycloꢀ
[6.2.1.02,6]undecꢀ3ꢀenꢀ7ꢀone (3). Methyl diazoacetate (0.24 g,
2.4 mmol) was added to a solution of levoglucosenone (1) (0.19 g,
1.5 mmol) in CH2Cl2 (4 mL) and this was left for 4 days at room
temperature, monitoring the reaction course by 1H NMR
spectroscopy. After evaporation of the solvent in vacuo, pyrazoꢀ
line 3 (0.20 g, 58%) was isolated by preparative TLC on SiO2
(benzene—AcOEt, 1 : 3, Rf 0.6) with 95% purity as a colorless
oily liquid. MS m/z (Irel (%)): 226 (8) [M]+, 195 (6)
[M – OMe]+, 152 (76), 139 (33), 95 (100), 59 (32). H NMR
1
Compound 17 was isolated by preparative TLC on
(CDCl3), δ: 3.71 (dd, 1 H, H(2), J2,6 = 11.2 Hz, J1,2 = 1.0 Hz);
3.88 (s, 3 H, ОMe); 4.02 (dd, 1 H, exoꢀH(10), 2J = 7.7 Hz,
3J = 4.7 Hz); 4.11 (dd, 1 H, endoꢀH(10), 2J = 7.7 Hz,
3J = 1.0 Hz); 4.50 (dd, 1 H, H(6), J2,6 = 11.2 Hz, J6,8 1.0 Hz);
5.16 (br.s, 1 H, H(8)); 5.60 (br.d, 1 H, H(1), J1,10 = 4.7 Hz);
6.96 (br.s, 1 H, NH). 13C NMR (CDCl3), δ: 49.7 (C(2)); 52.6
(OMe); 62.6 (C(6)); 68.8 (C(10)); 71.7 (C(1)); 99.4 (C(8));
141.3 (C(3)); 162.9 (CОО); 198.4 (C=О). When aliquots were
taken after 1 and 3.5 h, the 1H NMR spectra showed the presence
(along with signals for 2ꢀpyrazoline 3) of the signals related to
1ꢀpyrazoline 2 (CDCl3), δ: 2.73 (br.dd, 1 H, H(2), J2,3 = 9.0 Hz
and J2,6 = 9.8 Hz); 3.93 (s, 3 H, ОMe); 3.90 (2 H(10), overlapped
with the sameꢀtype signals for levoglucosenone); 4.84 (br.d,
1 H, H(1), J1,10 = 4.4 Hz); 5.18 (d, 1 H, H(8), J6,8 ≈ 2.0 Hz);
5.35 (H(3), partially overlapped with the signal for levogluꢀ
cosenone); 5.86 (dd, 1 H, H(6), J2,6 = 9.8 Hz, J6,8 = 2.0 Hz).
Dimethyl 2,11ꢀdihydroxyꢀ1,9,10,18ꢀtetraazaꢀ4,13,21,22ꢀ
tetraoxaheptacyclo[9.7.1.12,7.13,6.112,15.010,20.016,19]docosaꢀ
8,17ꢀdieneꢀ8,17ꢀdicarboxylate (4). Methyl diazoacetate (320 mg,
3.2 mmol) and pyridine (25 mg, 0.3 mmol) were added to a
solution of levoglucosenone (203 mg, 1.6 mmol) in anhydrous
benzene (5 mL) and this was left for 2 days at room temperature.
Then, the solvent was evaporated in vacuo and the residue was
recrystallized from CCl4 to yield colorless fine crystalline powder
(343 mg, 95%) of compound 4 with admixture of 2ꢀpyrazoline 3
(∼4%), m.p. 127—129 °C. Found (%): C, 47.42; H, 4.56;
N, 12.06. C18H20N4O10. Calculated (%): C, 47.79; H 4.46;
N, 12.39. MS (ESI, CHCl3/MeOH), m/z (Irel (%)): 453 (5)
SiO2, its structure was confirmed by the 1H and 13C NMR
1
and mass spectral data. Thus in the H NMR spectrum
the signal at δ 4.32 related to the proton at C(4) in the
starting diazoketone 16 disappears with simultaneous
simplification of the signals for the H(3) and H(5) proꢀ
tons. In the fiveꢀmembered ring of spirane 17 formed, the
signals for the protons of the methylene fragments are
found in different regions of the spectrum and have
different multiplicity: the lowꢀfield signal for the OCH2
fragment resonates as a singlet, whereas the signal for the
protons at C(4´), appears as two doublets with the spinꢀ
spin coupling constant 2J of 18.7 Hz.
In conclusion, we synthesized and described a numꢀ
ber of levoglucosenone derivatives including those with
a fused cyclopropane fragment in the molecule and
developed procedures for their synthesis. A possibility of
intramolecular carbeneꢀtype transformations of levoꢀ
glucosenone diazocarbonyl derivative with the formation
of new spirane structure has been demonstrated. In all the
cases, an efficient face discrimination due to the presence
of the anhydro bridge and influence of the acetal oxygen
atoms provides high regioꢀ and stereoselectivity of the
reactions described, which in most cases give rise to only
one isomer.
1
[M + H]+, 227 (100) [M/2 + H]+. H NMR (CDCl3), δ: 3.32
Experimental
(ddd, 1 H, H(7), J7,20 = 10.8 Hz, J ≈ 1.2 Hz); 3.48 (ddd, 1 H,
H(16), J16,19 = 12.0 Hz, J ≈ 0.9 Hz); 3.83 and 3.87 (both s,
3 H each, 2 OMe); 3.85 (dd, 1 H, endoꢀH(14), 2J = 7.9 Hz,
3J = 1.6 Hz); 3.90 (dd, 1 H, exoꢀH(5), 2J = 7.6 Hz, 3J = 4.8 Hz);
3.93 (dd, 1 H, exoꢀH(14), 2J = 7.9 Hz, 3J = 6.1 Hz); 4.01
(br.d, 1 H, endoꢀH(5), 2J = 7.6 Hz); 4.32 (d, 1 H, H(19),
3J = 12.0 Hz); 4.61 (d, 1 H, H(20), J7,20 = 10.8 Hz); 4.99 (br.dd,
1 H, H(15), 3J = 6.1 Hz, 3J = 1.6 Hz); 5.24 (br.s, 1 H,
H(12)); 5.26 (d, 1 H, H(3), J3,6 = 1.2 Hz); 5.56 (br.d, 1 H, H(6),
1H, 13C, and 14N NMR spectra were recorded on a Bruker
AVANCE II 300 spectrometer (300, 75.5 and 21.7 MHz,
respectively) for solutions in CDCl3 or DMSOꢀd6 containing
0.05% Me4Si as the internal standard. Mass spectra were
recorded on a Finnigan MAT INCOSꢀ50 (EI, 70 eV, direct
inlet) and Finnigan LCQ (ESI) instruments. Optical rotation
was measured on a PerkinꢀElmer 341 polarimeter at 20 °C

332
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
Novikov et al.
3J = 4.8 Hz); 5.10 and 7.65 (both br.s, 1 H each, 2 OH).
13C NMR (CDCl3), δ: 47.8 and 49.6 (C(7) and C(16)); 52.2 and
52.7 (2 OMe); 65.1 and 67.8 (C(19) and C(20)); 68.6 and 69.3
(C(5) and C(14)); 70.3 and 70.6 (C(6) and C(15)); 97.6 and 99.7
(C(2) and C(11)); 99.5 and 100.2 (C(3) and C(12)); 140.3 and
145.9 (C(8) and C(17)); 161.7 and 162.7 (2 COO).
CH2, 2J = 16.4 Hz, 4J = 1.2 Hz); 3.76 (s, 3 H, OMe); 3.90 (dd,
1 H, endoꢀH(7), 2J = 7.1 Hz, J = 1.0 Hz); 3.96 (dd, 1 H,
exoꢀH(7), 2J = 7.1 Hz, 3J = 4.7 Hz); 5.04 (br.d, 1 H, H(1),
J = 4.7 Hz); 5.36 (d, 1 H, H(5), J = 1.5 Hz); 5.97 (m, 1 H,
H(3)). 13C NMR (CDCl3), δ: 37.4 (CH2); 52.7 (OMe); 67.3
(C(7)); 75.0 (C(1)); 100.1 (C(5)); 125.3 (C(3)); 156.0 (C(2));
169.0 (COO); 188.8 (C(4)).
Dimethyl 2ꢀacetoxyꢀ11ꢀhydroxyꢀ1,9,10,18ꢀtetraazaꢀ4,13,
21,22ꢀtetraoxaheptacyclo[9.7.1.12,7.13,6.112,15.010,20.016,19]ꢀ
docosaꢀ8,17ꢀdieneꢀ8,17ꢀdicarboxylate (5). Acetyl chloride
(47 mg, 0.6 mmol) and pyridine (47 mg, 0.6 mmol) were added
to a solution of dimer 4 (91 mg, 0.2 mmol) in CH2Cl2 (5 mL)
and this was stirred for 6 h at 20 °C. The reaction mixture was
quenched with water, extracted twice with CH2Cl2, dried with
anhydrous MgSO4, and concentrated in vacuo. After recrystalꢀ
lization from diethyl ether, acetate 5 was obtained (87 mg, 88%)
as colorless crystals, m.p. 93—94 °C. Found (%): C, 48.21;
H, 4.26. C20H22N4O11. Calculated (%): C, 48.59; H 4.49.
MS, m/z (Irel (%)): 326 (2), 283 (6), 268 (11), 226 (20), 194
7,9ꢀDioxatricyclo[4.2.1.02,4]nonanꢀ5ꢀol (9). An ethereal
solution of diazomethane (0.56 M, 268 mL, 0.15 mol) was added
dropwise to a solution of 6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀenꢀ4ꢀol
(8) (10.2 g, 0.08 mol) and Pd(acac)2 (49 mg, 0.16 mmol) in
CH2Cl2 (50 mL) at 0—5 °C with gentle stirring over 30 min and
stirring was continued for another 1 h. Then, the reaction mixture
was filtered, the solvent was evaporated, and the residue distilled
in vacuo to yield compound 9 (10.8 g, 95%) as colorless needleꢀ
like crystals hygroscopic in air, b.p. 41—42 °C (0.03 Torr),
20
m.p. 48—49 °C, [α]D –90.0° (c 0.54; CHCl3). Found (%):
C, 59.12; H, 7.22. C7H10O3. Calculated (%): C, 59.14; H, 7.10.
1
(75), 152 (100). H NMR (CDCl3), δ: 2.35 (s, 3 H, Me); 3.37
MS, m/z (Irel (%)): 96 (51) [M – H2O – CO]+; 95 (52);
(d, 1 H, H(16), 3J = 12.3 Hz); 3.46 (dt, 1 H, H(7), 3J = 10.4 Hz,
J = 1.2 Hz); 3.78 (dd, 1 H, exoꢀH(5) or exoꢀH(14), 2J = 8.0 Hz,
3J = 1.8 Hz); 3.86 and 3.92 (both s, 3 H each, 2 OMe); 3.91 (m,
2 H, exoꢀH(5) or exoꢀH(14) and endoꢀH(5) or endoꢀH(14));
4.02 (d, 1 H, endoꢀH(5) or endoꢀH(14), 2J = 8.0 Hz); 4.45 (d,
1 H, H(19), 3J = 12.3 Hz); 4.93 (br.d, 1 H, H(15), 3J = 6.0 Hz);
5.11 (br.s, 1 H, OH); 5.27 and 5.31 (both s, 1 H each, H(3) and
H(12)); 5.43 (d, 1 H, H(20), 3J = 10.4 Hz); 5.52 (br.d, 1 H,
67 (100); 55 (51); 41 (85); 39 (89). H NMR (CDCl3), δ: 0.60
1
(m, 2 H, C(3)H2); 0.83 and 1.02 (both m, 1 H each, H(2)
and H(4)); 2.33 (d, OH, J = 11.6 Hz); 3.69 (dd, 1 H, H(5),
J5,6 = 3.5 Hz, J = 11.6 Hz); 3.82 (dd, 1 H, exoꢀH(8),
J1,8ꢀexo = 4.1 Hz, 2J = 6.7 Hz); 4.01 (d, 1 H, endoꢀH(8),
2J = 6.7 Hz); 4.62 (d, 1 H, H(1), J1,8ꢀexo = 4.1 Hz); 5.16 (d, 1 H,
H(6), J5,6 = 3.5 Hz). 13C NMR (CDCl3), δ: 6.6 (C(3)); 13.4 and
14.8 (C(2) and C(4)); 67.1 (C(1)); 70.9 (C(8)); 71.3 (C(5));
99.6 (C(6)).
3
H(6), J = 4.6 Hz). 13C NMR (CDCl3), δ: 22.3 (Me); 48.9 and
49.6 (C(7) and C(16)); 52.6 and 53.0 (2 OMe); 61.1 and 66.8
(C(19) and C(20)); 68.3 and 69.0 (C(5) and C(14)); 70.0 and
70.5 (C(6) and C(15)); 96.2 (C(11)); 99.9 (C(2)); 100.0 and
101.0 (C(3) and C(12)); 145.1 and 145.9 (C(8) and C(17));
162.0 and 162.1 (2 COO).
7,9ꢀDioxatricyclo[4.2.1.02,4]nonanꢀ5ꢀone (10). Freshly
prepared activated manganese dioxide was added in excess
(10—11 g) to a solution of 7,9ꢀdioxatricyclo[4.2.1.02,4]nonanꢀ
5ꢀol (9) (0.50 g, 3.5 mmol) in CH2Cl2 (50 mL) and this
was stirred for 20 h at room temperature. Solids were filtered
off, washed with ethyl acetate (30 mL) and the solvents were
evaporated in vacuo. The product was purified by column
chromatography on SiO2 (eluent, benzene : AcOEt, 7 : 1) to
yield ketone 10 (0.45 g, 92%) as a colorless oil. MS, m/z
(Irel (%)): 140 (12) [M]+, 113 (18) [M – C2H3]+, 94 (69), 83
(45), 66 (100), 55 (94), 39 (83). 1H NMR (CDCl3), δ: 1.16 (ddd,
3ꢀMethoxycarbonylꢀ7,9ꢀdioxatricyclo[4.2.1.02,4]nonanꢀ
5ꢀone (6) and 2ꢀ(2ꢀmethoxyꢀ2ꢀoxoethyl)ꢀ6,8ꢀdioxabicycloꢀ
[3.2.1]octꢀ2ꢀenꢀ4ꢀone (7). A solution of levoglucosenone (1)
(101 mg, 0.8 mmol) and methyl diazoacetate (480 mg, 4.8 mmol)
in benzene (8 mL) was refluxed for 20 h under argon. Then, the
reaction mixture was concentrated in vacuo and the residue was
passed through a column with SiO2 eluting with diethyl ether to
obtain a colorless oily liquid (119 mg, 75%), which was a 1.8 : 1
mixture of compounds 6 and 7 (1H NMR data). The mixture
obtained was separated by preparative TLC on SiO2 with threeꢀ
fold development (benzene—AcOEt, 4 : 1) to yield compound 7
(24 mg) with Rf = 0.27 and compound 6 (45 mg) with Rf = 0.32
(the content of the major isomer in each of them was ∼90%), as
well as a fraction with approximately the same ratio of comꢀ
pounds 6 and 7 as in the starting mixture.
3
1 H, antiꢀH(3), 2J = 4.8 Hz, Jcis = 7.6 Hz and 9.9 Hz); 1.43
(dt, 1 H, synꢀH(3), 2J = 4.8 Hz, 3Jtrans = 5.0 Hz); 1.58 and 1.71
(both m, 1 H each, H(2) and H(4)); 3.88 (dd, 1 H, exoꢀH(8),
2J = 6.8 Hz, J1,8ꢀexo = 4.7 Hz); 4.03 (d, 1 H, endoꢀH(8),
2J = 6.8 Hz); 4.77 (d, 1 H, H(1), J1,8ꢀexo = 4.7 Hz); 4.95 (s, 1 H,
H(6)). 13C NMR (CDCl3), δ: 9.1 (C(3)); 14.8 and 20.0 (C(2)
and C(4)); 68.5 (C(8)); 71.3 (C(1)); 99.9 (C(6)), 197.4 (C=O).
4ꢀ(Methoxycarbonylmethoxy)ꢀ6,8ꢀdioxabicyclo[3.2.1]octꢀ
2ꢀene (11a). Method A. A Rh2(OAc)4 catalyst (68 mg, 0.15 mmol)
was added to a solution of 6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀenꢀ4ꢀol
(8) (9.61 g, 0.075 mol) in CH2Cl2 (230 mL) followed by a
dropwise addition of a solution of methyl diazoacetate (15.0 g,
0.15 mol) in CH2Cl2 (30 mL) with stirring at 20 °C over 3 h.
The reaction mixture was stirred for another 1 h, concentrated
in vacuo to 2/3 of the original volume, and passed through a
short layer of silica gel. The solvent was evaporated and the
residue was distilled in vacuo to yield ester 11a (12.9 g, 86%) as a
Compound 6. MS, m/z (Irel (%)): 198 (3) [M]+, 170 (9), 155
(19), 124 (17), 111 (31), 95 (29), 83 (73), 59 (58), 39 (100).
1H NMR (CDCl3), δ: 2.04 (ddd, 1 H, H(2), J2,4 = 7.9 Hz,
J2,3 = 4.1 Hz, J1,2 = 1.4 Hz); 2.30 (br.dd, 1 H, H(4), J2,4 = 7.9 Hz,
J3,4 = 4.1 Hz); 2.54 (t, 1 H, H(3), Jtrans = 4.1 Hz); 3.74 (s, 3 H,
OMe); 3.92 (dd, 1 H, exoꢀH(8), 2J = 7.1 Hz, 3J = 4.7 Hz);
4.08 (d, 1 H, endoꢀH(8), 2J = 7.1 Hz); 4.90 (br.d, 1 H, H(1),
J1,8a = 4.7 Hz); 5.01 (br.s, 1 H, H(6)). 13C NMR (CDCl3), δ:
22.1, 22.5 and 22.6 (C(2), (C(3) and C(4)); 52.5 (OMe); 68.4
(C(8)); 70.7 (C(1)); 99.7 (C(6)); 170.8 (COO); 193.6 (C(5)).
Compound 7. MS, m/z (Irel (%)): 198 (8) [M]+, 170 (67),
153 (28), 138 (22), 124 (59), 110 (80), 81 (83), 59 (100), 39
20
colorless oily liquid, b.p. 109—112 °C (0.03 Torr), [α]D –23.5°
(c 0.39; CHCl3). Found (%): C, 53.70; H, 5.87. C9H12O5.
Calculated (%): C, 54.00; H, 6.04. MS, m/z (Irel (%)): 200 (2)
1
[M]+, 155 (12), 127 (12), 97 (21), 81 (90), 39 (100). H NMR
1
(100). H NMR (CDCl3), δ: 3.40 and 3.48 (both dd, 1 H each,
(CDCl3), δ: 3.76 (s, 3 H, OMe); 3.78 (br.dd, 1 H, exoꢀH(7),

Reactions of levoglucosenone with diazo compounds Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
333
2J = 6.5 Hz, 3J = 4.1 Hz); 3.94 (br.d, 1 H, endoꢀH(7),
2J = 6.5 Hz); 4.28 and 4.30 (both d, 1 H each, OCH2,
2J = 16.5 Hz); 4.36 (m, 1 H, H(4)); 4.68 (dd, 1 H, H(1),
J1,2 ≈ J1,7a = 4.1 Hz); 5.65 (br.dd, 1 H, H(5), J4,5 ≈ J3,5 = 2.3 Hz);
5.78 (ddd, 1 H, H(3), J2,3 = 9.8 Hz, J3,4 ≈ J3,5 = 2.3 Hz); 6.08
(ddd, 1 H, H(2), J2,3 = 9.8 Hz, J1,2 = 4.1 Hz, J2,4 = 1.1 Hz).
13C NMR (CDCl3), δ: 51.3 (OMe); 65.5 (OCH2); 70.8 (C(7));
70.9 (C(1)); 76.6 (C(4)); 99.7 (C(5)); 125.2 (C(3)); 131.5 (C(2));
170.3 (COO).
Method B. A solution of potassium tertꢀbutoxide (0.30 g,
2.6 mmol) and unsaturated alcohol 8 (0.31 g, 2.4 mmol) in
anhydrous dimethoxyethane (4 mL) was stirred under argon
for 30 min, then a solution of methyl bromoacetate (0.38 g,
2.5 mmol) in dimethoxyethane (1 mL) was added and this
was stirred for another 2 h. A precipitate formed was filtered
off, washed with CHCl3 (2×5 mL), the filtrate was concentrated
in vacuo, and the residue was separated by column chromatoꢀ
graphy on SiO2 (benzene—AcOEt, 1 : 1) to yield compound 11a
(0.36 g, 75%) as a colorless oil identical to the sample obtained
by method A.
70.2 (C(1)); 70.6 (C(8)); 74.6 (C(5)); 98.1 (C(6)); 170.4 and
172.8 (2 COO).
5ꢀMethoxycarbonylmethoxyꢀ7,9ꢀdioxatricyclo[4.2.1.02,4]ꢀ
nonane (13). An ethereal solution of diazomethane (0.57 M,
158 mL, 0.09 mol) was added to a stirred solution of compound
11a (10.0 g, 0.05 mol) and Pd(acac)2 (76 mg, 0.25 mmol) in
dichloromethane (60 mL) at 0—5 °C over 2 h and this was
stirred for another 1 h. The reaction mixture was filtered through
a short layer of alumina, the solvents were evaporated, and the
residue was distilled in vacuo of an oil pump to obtain compound
13 (10.1 g, 95%) as a colorless oily liquid, b.p. 121—125 °C
20
(0.01 Torr), [α]D –41.2° (c 0.39; CHCl3). Found (%):
C, 56.45; H, 6.85. C10H14O5. Calculated (%): C, 56.07; H, 6.59.
MS, m/z (Irel (%)): 168 (5) [M – H2O – CO]+; 95 (40),
78 (100), 67 (40). 1H NMR (CDCl3), δ: 0.48 (dt, 1 H, synꢀH(3),
2J = 4.9 Hz, Jtrans ≈ 5.0 Hz); 0.69 (dd, 1 H, antiꢀH(3),
2J = 4.9 Hz, Jcis = 7.8 Hz and 9.4 Hz); 0.96 and 1.02 (both m,
1 H each, H(2) and H(4)); 3.55 (d, 1 H, H(5), J5,6 = 3.1 Hz);
3.77 (s, 3 H, OMe); 3.85 (dd, 1 H, exoꢀH(8), J1,8ꢀexo = 4.1 Hz,
2J = 6.7 Hz); 4.11 (d, 1 H, endoꢀH(8), 2J = 6.7 Hz); 4.25 and
4.27 (both d, 1 H each, OCH2, 2J = 16.6 Hz); 4.61 (br.d, 1 H,
H(1), J1,8ꢀexo = 4.1 Hz); 5.35 (dd, 1 H, H(6), J5,6 = 3.1 Hz,
J4,6 = 1.3 Hz). 13C NMR (CDCl3), δ: 7.1 (C(3)); 10.2 and 14.7
(C(2) and C(4)); 51.9 (OMe); 66.4 (OCH2); 71.1 (C(8));
71.3 (C(1)); 76.1 (C(5)); 98.2 (C(6)); 170.8 (COO).
4ꢀMethoxycarbonylꢀ6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀene (14).
Ester 11b (10.1 g, 47 mmol) was added to an aqueous ethanolic
(1 : 1) solution of KOH (0.8 M, 200 mL) and this was refluxed
for 3 h. Ethanol was evaporated on a rotary evaporator, the
residue was washed with CH2Cl2 (3×50 mL), the aqueous layer
was acidified with 10% aq. hydrochloric acid to pH 2.5—3, the
solution was halfꢀconcentrated in vacuo, and repeatedly extracted
with ethyl acetate (8×80 mL). The combined organic extracts
were dried no less than for 3 h with anhydrous MgSO4, then the
solvent was evaporated on a rotary evaporator, and the residue
was dried in vacuo of 0.01 Torr to obtain acid 14 (8.39 g, 96%)
with ∼95% purity as a light orange oil, which darkens in
air. MS, m/z (Irel (%)): 141 (6) [M – COOH]+, 127 (3)
[M – CH2COOH]+, 111 (4) [M – OCH2COOH]+, 102 (9), 81
(100), 53 (46). 1H NMR (CDCl3), δ: 3.80 (ddd, 1 H, exoꢀH(7),
2J = 6.6 Hz, J1,7ꢀexo = 4.2 Hz, J = 1.1 Hz); 3.97 (d, 1 H,
endoꢀH(7), 2J = 6.6 Hz); 4.26 and 4.34 (both d, 1 H each,
OCH2, 2J = 16.8 Hz); 4.42 (m, 1 H, H(4)); 4.69 (dd, 1 H, H(1),
J1,2 ≈ J1,7ꢀexo = 4.2 Hz); 5.68 (br.dd, 1 H, H(5), J4,5 = 2.4 Hz,
J3,5 = 2.2 Hz); 5.75 (ddd, 1 H, H(3), J2,3 = 9.9 Hz,
4ꢀEthoxycarbonylmethoxyꢀ6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀene
(11b). This was prepared as a liquid similarly to the preceding
experiment (method B), from alcohol 8 (10.2 g, 0.08 mol),
ethyl bromoacetate (15.0 g, 0.09 mol), and ButOK (10.1 g,
0.09 mol). The residue was distilled in vacuo to yield comꢀ
pound 11b (12.5 g, 73%) as a colorless oil, b.p. 118—121 °C
20
(0.03 Torr), [α]D –22.1° (c 0.39; CHCl3). Found (%):
C, 55.80; H, 6.79. C10H14O5. Calculated (%): C, 56.07; H, 6.59.
MS, m/z (Irel (%)): 214 (58) [M]+, 169 (12), 127 (22), 81 (100).
1H NMR (CDCl3), δ: 1.29 (t, 3 H, Me, J = 7.1 Hz); 3.79 (ddd,
1 H, exoꢀH(7), 2J = 6.6 Hz, 3J = 4.2 Hz, J = 1.3 Hz); 3.96 (br.d,
1 H, endoꢀH(7), 2J = 6.6 Hz); 4.21 and 4.27 (both d, 1 H each,
OCH2, J = 16.5 Hz); 4.23 (q, 2 H, COOCH2, J = 7.1 Hz); 4.38
(m, 1 H, H(4)); 4.67 (dd, 1 H, H(1), J1,2 ≈ J1,7ꢀexo = 4.2 Hz);
5.69 (dd, 1 H, H(5), J4,5 = 2.4 Hz, J3,5 = 2.2 Hz); 5.78 (ddd,
1 H, H(3), J2,3 = 9.9 Hz, J3,4 ≈ J3,5 = 2.2 Hz); 6.17 (ddd, 1 H,
H(2), J2,3 = 9.9 Hz, J1,2 = 4.2 Hz, J2,4 = 1.4 Hz). 13C NMR
(CDCl3), δ: 14.3 (Me); 61.1 (COOCH2); 66.4 (OCH2); 71.5
(C(7)); 71.6 (C(1)); 77.3 (C(4)); 100.4 (C(5)); 126.0 (C(3));
131.9 (C(2)); 170.6 (C=O).
3ꢀMethoxycarbonylꢀ5ꢀmethoxycarbonylmethoxyꢀ7,9ꢀdioxaꢀ
tricyclo[4.2.1.02,4]nonane (12). A Rh2(OAc)4 catalyst (5.5 mg,
0.012 mmol) was added to a solution of compound 11a (0.50 g,
2.5 mmol) in CH2Cl2 (10 mL), followed by a slow addition of
methyl diazoacetate (1.20 g, 12 mmol) in CH2Cl2 (3 mL) over
3 h with stirring. The reaction mixture was stirred for another
2 h at 30 °C, then, passed through a short layer of silica gel, the
sorbent was washed with CH2Cl2 (2 mL), and the eluate was
concentrated in vacuo. The residue was separated by column
chromatography on SiO2 (eluent, benzene—AcOEt, 1 : 1). The
starting 11a (0.22 g, ∼45%) and compound 12 (0.29 g, 42%) as a
colorless oil were isolated. 1H NMR (CDCl3), δ: 1.63 (ddd, 1 H,
H(4), J2,4 = 9.1 Hz, J3,4 = 4.4 Hz, J4,6 = 1.5 Hz); 1.69 (br.dd,
1 H, H(2), J2,4 = 9.1 Hz, J2,3 4.4 Hz); 1.80 (dd, 1 H, H(3),
J2,3 ≈ J3,4 = 4.4 Hz); 3.63 (d, 1 H, H(5), J5,6 = 3.1 Hz); 3.70
and 3.77 (both s, 3 H each, 2 OMe); 3.86 (dd, 1 H, exoꢀH(8),
2J = 7.1 Hz, J1,8ꢀexo = 4.1 Hz); 4.14 (d, 1 H, endoꢀH(8),
2J = 7.1 Hz); 4.23 and 4.29 (both d, 1 H each, OCH2, 2J = 16.6 Hz);
4.65 (br.d, 1 H, H(1), J1,8ꢀexo = 4.1 Hz); 5.40 (br.dd, 1 H, H(6),
J5,6 = 3.1 Hz, J4,6 = 1.5 Hz). 13C NMR (CDCl3), δ: 20.3 (C(4));
22.0 (C(3)); 24.3 (C(2)); 51.92 and 51.96 (2 OMe); 66.3 (OCH2);
J3,4
≈ J3,5 = 2.2 Hz); 6.21 (ddd, 1 H, H(2), J2,3 = 9.9 Hz,
J1,2 = 4.2 Hz, J = 1.4 Hz); 8.70 (br.s, 1 H, COOH). 13C NMR
(CDCl3), δ: 64.6 (OCH2); 70.9 (C(7)); 71.1 (C(1)); 76.5 (C(4));
99.8 (C(5)); 125.1 (C(3)); 131.6 (C(2)); 174.3 (COO).
4ꢀ(3ꢀDiazoꢀ2ꢀoxopropoxy)ꢀ6,8ꢀdioxabicyclo[3.2.1]octꢀ2ꢀene
(16). A solution of acid 14 (0.97 g, 5.2 mmol) in a mixture of
anhydrous benzene and dimethoxyethane (3 : 1, 30 mL) was
added dropwise to a solution of distilled oxalyl chloride (0.66 g,
5.2 mmol) in anhydrous benzene (15 mL) containing pyridine
(1 drop) with stirring under dry nitrogen at 18 °C over 30 min
and this was stirred for 2.5 h. Then a solution of triethylamine
(0.51 g, 5 mmol) in anhydrous benzene (3 mL) was added to the
reaction mixture at 0 °C over 10 min and the mixture obtained
was added dropwise without filtration to a stirred ethereal
solution of diazomethane (25 mL, ∼15 mmol) at 0 °C over
30 min. The mixture was stirred for an additional 1 h at 20 °C,

334
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Novikov et al.
a precipitate formed was filtered off and the solvents were
evaporated in vacuo. The oily red residue was extracted with
Et2O (3×20 mL), the combined extracts were concentrated
in vacuo, and the residue was purified by column chromatography
on SiO2 (eluent, Et2O) to yield diazo ketone 16 (0.61 g, ∼55%)
with ~95% purity as a yellow oil. MS, m/z (Irel (%)): 182 (1.5)
[M – N2]+, 137 (14), 108 (26), 95 (43), 81 (100), 78 (79),
55 (98). 1H NMR (CDCl3), δ: 3.80 (ddd, 1 H, exoꢀH(7),
2J = 6.6 Hz, J1,7ꢀexo = 4.2 Hz, J = 1.1 Hz); 3.96 (d, 1 H,
endoꢀH(7), 2J = 6.6 Hz); 4.14 and 4.21 (both d, 1 H each,
OCH2, 2J = 15.9 Hz); 4.32 (m, 1 H, H(4)); 4.68 (dd, 1 H, H(1),
J1,2 ≈ J1,7ꢀexo = 4.2 Hz); 5.61 (dd, 1 H, H(5), J4,5 = 2.4 Hz,
J3,5 = 2.2 Hz); 5.71 (ddd, 1 H, H(3), J2,3 = 9.8 Hz,
J3,4 ≈ J3,5 = 2.2 Hz); 5.88 (br.s, 1 H, HCN2); 6.19 (ddd, 1 H,
H(2), J2,3 = 9.8 Hz, J1,2 = 4.2 Hz, J = 1.5 Hz). 13C NMR
(CDCl3), δ: 53.4 (CN2); 71.4 (C(1)); 71.5 (C(7)); 72.5 (OCH2);
77.6 (C(4)); 99.9 (C(5)); 125.3 (C(3)); 131.1 (C(2)); 193.4
(C=O). 14N NMR (CDCl3), δ: –119.0 (=N); –9.7 (HC=N).
1´,6,8ꢀTrioxaspiro[bicyclo[3.2.1]octꢀ2ꢀeneꢀ4,4´ꢀcyclopentanꢀ
3´ꢀone] (17). Freshly prepared CuCl (5 mg) was added to a
solution of diazo ketone 16 (21 mg, 0.1 mmol) in CH2Cl2
(10 mL) and this was refluxed for 1 h. Then, the reaction mixture
was filtered, the solvent was evaporated in vacuo, and the oily
residue obtained was separated by preparative TLC on SiO2
(eluent, AcOEt) to yield compound 17 (10 mg, 55%) as a
colorless oil, Rf = 0.79. MS, m/z (Irel (%)): 181 (2) [M – H]+,
153 (2), 137 (27), 86 (60), 84 (100), 79 (44). 1H NMR (CDCl3),
δ: 2.48 and 2.70 (both d, 1 H each, H(4´), 2J = 18.7 Hz); 3.82
(dd, 1 H, exoꢀH(7), 2J = 6.6 Hz, J1,7ꢀexo = 4.1 Hz); 3.96 (d, 1 H,
endoꢀH(7), 2J = 6.6 Hz); 4.14 (br.s, 2 H, H(2´)); 4.71 (dd,
1 H, H(1), J1,7ꢀexo = 4.1 Hz, J1,2 = 4.3 Hz); 5.39 (d, 1 H,
H(5), J3,5 = 2.3 Hz); 5.74 (dd, 1 H, H(3), J2,3 = 10.0 Hz,
J3,5 = 2.3 Hz); 6.17 (dd, 1 H, H(2), J2,3 = 10.0 Hz, J1,2 = 4.3 Hz).
13C NMR (CDCl3), δ: 45.4 (C(4´)), 70.4 and 70.6 (C(7) and
C(2´)), 71.6 (C(1)), 76.2 (C(4)), 102.5 (C(5)), 128.2 (C(2));
130.6 (C(3)); 212.9 (C=O).
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This work was financially supported by the Division of
Chemistry and Materials Science of the Russian Academy
of Sciences (Program for Basic Research “Biоmolecular
and Medical Chemistry") and by the Council on Grants
at the President of the Russian Federation (Program for
the State Support of Leading Scientific Schools of RF,
Grant NShꢀ3237.2008.3).
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Received April 28, 2008