Unusual removal of the ethylene ketal protection from 2,3-dichloro-4, 4-ethylenedioxycyclopent-2-en-1-one under alkaline conditions. Simple synthesis of naturally occurring cyclopentenedione analogs

Article abstract of DOI:10.1007/s11172-009-0103-6

A reaction of 2,3-dichloro-4,4-ethylenedioxycyclopent-2-en-1-one with MeONa in MeOH to furnish 2-chloro-3-hydroxycyclopent-2-en-1,4-dione has been studied. The latter under the action of CH₂N₂ has been converted to the corresponding

Full text of DOI:10.1007/s11172-009-0103-6

Russian Chemical Bulletin, International Edition, Vol. 58, No. 4, pp. 838—843, April, 2009
838
Unusual removal of the ethylene ketal protection from 2,3ꢀdichloroꢀ
4,4ꢀethylenedioxycyclopentꢀ2ꢀenꢀ1ꢀone under alkaline conditions.
Simple synthesis of naturally occurring cyclopentenedione analogs
F. A. Gimalova, V. A. Egorov, N. A. Ivanova, A. A. Fatykhov, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Scientific Center of the Russian Academy of Sciences,
71 prosp. Octyabrya, 450054 Ufa, Russian Federation.
Fax: +7 (347) 235 6066. Eꢀmail: bioreg@anrb.ru
A reaction of 2,3ꢀdichloroꢀ4,4ꢀethylenedioxycyclopentꢀ2ꢀenꢀ1ꢀone with MeONa in MeOH
to furnish 2ꢀchloroꢀ3ꢀhydroxycyclopentꢀ2ꢀenꢀ1,4ꢀdione has been studied. The latter under the
action of CH2N2 has been converted to the corresponding enol ether. This methodology has
been used for the synthesis of 4ꢀchloroꢀ5ꢀmethoxyꢀ2ꢀcinnamylidenecyclopentꢀ4ꢀenꢀ1,3ꢀdiꢀ
ones and related compounds starting from the parent dichlorocyclopentenone.
Key words: 2,3ꢀdichloroꢀ4,4ꢀethylenedioxycyclopentꢀ2ꢀenꢀ1ꢀone, ketals, aldol reaction,
organochlorine compounds.
Cyclic ketone acetals, in particular 1,3ꢀdioxolanes, are
(Scheme 2). Initially, we planed to obtain vinylog ether 5
by the AdNE substitution of the Cl atom at C(3) of dichloꢀ
rocyclopentenone 1 for the methoxide anion. Rather, this
reaction afforded a new compound, viz., the enolized cyꢀ
clopentanetrione derivative 6, in almost quantitative yield.
The latter was converted into the enol ether 7 upon treatꢀ
ment with CH2N2.
inert in water and alcohol solutions of strong alkalis1 and
can be hydrolyzed upon the action of mineral2,3 and orꢀ
ganic acids,4,5 Py(HF)x,6 Lewis acids1,2,7 (Al, Ti, B, Pd
compounds, etc.), SiO2,8 Me3SiI,9 LiBF4,10 dimethyldioxꢀ
irane,11 etc.
We encountered the problem with hydrolysis of dioxꢀ
olane protecting group12,13 during the search for mild and
convenient methods for the transformation of chlorineꢀ
containing 4,4ꢀethylenedioxycyclopentenones 1 and 2 into
corresponding cyclopentenediones 3 and 4 (Scheme 1).
Testing some of the procedures mentioned above for these
purposes was unsuccessful. It turned out that hydrolysis of
the ethylene ketal protecting group of compounds 1 and 2
is successful only under extreme conditions under the acꢀ
tion of 98% aq. H2SO4, as it was shown earlier14 for ketal 2.
Scheme 2
Scheme 1
R = H (1, 3), Cl (2, 4)
Unlike for compound 1, the reaction of trichlorocyꢀ
clopentenone 2 with MeONa took several directions and
was accompanied by formation of a mixture of products
and, therefore, we did not study it. As it can be seen, the
formal result of the reaction of ketal 1 with MeONa is
i. 98% aq. H2SO4, 0 °C, 1 h.
We observed an interesting example of nontrivial reꢀ
moval of the dioxolane protecting group during the reacꢀ
tion of dichlorocyclopentenone 1 with MeONa in MeOH
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 821—825, April, 2009.
1066ꢀ5285/09/5804ꢀ0838 © 2009 Springer Science+Business Media, Inc.

Cyclopentꢀ4ꢀeneꢀ1,3ꢀdiones
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
839
Scheme 3
Scheme 4
a "double hydrolysis" of expected compound 5 in the dioxꢀ
olane and enol ether parts. We will discuss a possible verꢀ
sion of this interesting transformation below (Scheme 3).
It is obvious that the initial attack of the MeO anion on the
activated enone system 1 generates carbanion A, which by
trivial removal of the Cl atom at C(3) should have led to
the product of AdNE substitution 5.15 However, the reacꢀ
tion takes another way. The initial carbanion A is convertꢀ
ed into the isomeric carbanion В, which after the dioxꢀ
olane ring opening and removal of the MeCl (or vice versa)
gives enedione C. Aqueous treatment of the reaction mixꢀ
ture (without acidification) quickly leads to trione 6.
A facile dioxolane ring opening16 during the thermal
Claisen rearrangement of allyl vinyl ether 8 into dione 9
should be noted as a precedent close to the cycle of transꢀ
formations under discussion (Scheme 4). We also found
an unusual example of elimination of MeOCl from comꢀ
pound 10 with generation of the corresponding cyclopenꢀ
tadienone derivative in Ref. 17. Unlike suggested intermeꢀ
diate C, diketone 9 has been isolated in the individual
state, it is hydrolytically stable enough, it can stand aqueous
treatment and chromatography on SiO2. As it can be seen
from the structures 9 and C, the latter has a labile H atom
at C(2) and, as cyclopentane triketones,18 should possess
strong acidic properties. It is likely that even upon aqueous
treatment of the reaction mixture, some sort of acidificaꢀ
tion of the medium and hydrolysis of the enol ether C take
place. In point of fact, the trione 6, partially existing in the
reaction medium, after addition of water initiates fast hyꢀ
drolysis of the intermediate C ("selfꢀcatalysis").
to form the crotonization 13 (as a mixture of Z/Eꢀisomers
in the ratio ~6 : 5) and substitution 14 products. Comꢀ
pound 13 upon treatment with MeONa and subsequent
methylation of the enol 11 obtained by the action of
CH2N2 was converted into enol ether 12. Compound 12
can be synthesized by similar for 1 crotonization of the
vinyl ether 7, however, this reaction is accompanied
by intensive resinification. The higher reactivity of the
dichloroꢀsubstituted double bond as compared to the side
bonds in compound 13 is confirmed by the chemoselective
formation of the vinylog amide 15 in the reaction with
morpholine.
Further, we used the "C(3)ꢀenol formation—C(4)ꢀdeꢀ
ketalization" version developed for ketal 1 in the construcꢀ
tion of the 2ꢀcinnamylidenecyclopentenedione structures
11 and 12 (Scheme 5).
The condensation of ketone 1 lithium enolate with cinꢀ
namaldehyde and cinnamoyl chloride proceeds smoothly
Unexpected result was observed when acetic anhydride
was used in the condensation with dichloroketone 1. The
product of aldol condensation of two ketone molecules 1,
viz., a dimeric compound 16 as a mixture of Z,Eꢀisomers

840
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
Gimalova et al.
Scheme 5
Methyllucidone
R = H (11), Me (12)
Scheme 6
(Scheme 6) separable by column chromatography on SiO2,
was isolated in this case.
βꢀdiketone E, which is rapidly metallated with unreacted
enolate D to produce anion F capable to react with the
liberated ketone 1. The ketol G generated at this step
affords the E,Zꢀisomeric mixture 16 by the mechanism of
1,3ꢀdiketone cleavage through the cyclic oxetane H and
removal AcO– (see Scheme 7).
The compounds 11—15 obtained are considered by us
as close analogs of naturally occurring antifungal cycloꢀ
pentenediones coruscanones A and В,18 calitrone,19 stigꢀ
machamone,20 methyllucidone,21 etc.
Note that the dimer 16 is not formed in the conversion
1 → 16 without addition of Ac2O, as well as to the model
condensations of equimolar amounts of ketone 1 and its Li
enolate. Here, the role of Ac2O promoting the selfꢀconꢀ
densation of compound 1 is obvious. Apparently, the proꢀ
cess can be presented as Scheme 7.
In the initial step, the addition of Ac2O to a solution of
Li enolate D leads to the strong CH acid in form of

Cyclopentꢀ4ꢀeneꢀ1,3ꢀdiones
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
841
Scheme 7
1064, 1082, 1128, 1184, 1203, 1259, 1303, 1330, 1375, 1454,
1612, 1712, 1749, 2856, 2920, 2959, 3373. 1H NMR, δ: 3.76
(s, 2 H, CH2); 5.02 (s, 3 H, OMe). 13C NMR, δ: 42.03 (C(5)),
59.69 (OMe), 128.90 (C(2)), 164.46 (C(3)), 188.50, 191.47
(C(1), C(4)).
Experimental
IR spectra were recorded on a Specord Mꢀ80 and Shimadzu
IR Prestigeꢀ21 spectrophotometers for neat samples or in Nujol.
NMR spectra were recorded on a Bruker AMꢀ300 spectrometer
(1H, 300 MHz; 13C, 75.47 MHz) for solutions in CDCl3 using
Me4Si as the internal standard. Mass spectra were recorded on
a Thermo Finnigan MAT 95XP (the temperature of the ionizing
chamber was 200 °C, the temperature of the sample injection was
(6E,Z)ꢀ8,9ꢀDichloroꢀ6ꢀ(3ꢀphenylpropꢀ2(E)ꢀenylidene)ꢀ1,4ꢀ
dioxaspiro[4.4]nonꢀ8ꢀenꢀ7ꢀone (13). A solution of BuLi in hexꢀ
ane (0.86 M, 3.4 mL, 2.87 mmol) was added dropwise under
argon to a solution of Pri2NH (0.41 mL, 2.87 mmol) in anhyꢀ
drous THF (10 mL) cooled to –10 °C. The reaction mixture was
stirred for 15 min followed by a dropwise addition of a solution of
compound 1 (0.5 g, 2.39 mmol) in THF (3 mL). After 15 min,
the reaction mixture was cooled to –78 °C followed by a dropwise
addition of a solution of cinnamaldehyde (0.3 mL, 2.39 mmol) in
THF (6 mL), the mixture was stirred for 1 h at –78 °C and for 2 h
at ~20 °C, then, a saturated solution of NH4Cl, (2—3 mL) was
added and the stirring was continued for 10 min, then, THF was
evaporated, and the residue extracted with CHCl3. The comꢀ
bined organic layers were washed with brine, dried with MgSO4,
and concentrated. The residue was recrystallized from Et2O to
obtain compound 13 (0.60 g, 77%) as a mixture of isomers in the
ratio ~6 : 5 (determined from the correlation of integral intensiꢀ
ties of the signals for the protons at C(3´) atom).22 White powꢀ
der, m.p. 120—122 °C. IR, ν/cm–1: 690, 825, 908, 951, 983,
1004, 1126, 1161, 1186, 1450, 1460, 1571, 1599, 1614, 1632,
5—270 °C, the temperature was raised at the rate of 22 °C min–1
)
and Shimadzu LCMSꢀ2010 instruments (chemical ionization
under atmospheric pressure). The reaction course was moniꢀ
tored by TLC on Silufol and Sorbphil plates with visualization of
compounds by charring or in the alkaline solution of potassium
permanganate. The products synthesized were isolated by colꢀ
umn chromatography on silica gel (30—60 g of adsorbent per 1 g
of compound), freshly distilled solvents were used as the eluents.
2ꢀChloroꢀ3ꢀhydroxycyclopentꢀ2ꢀenꢀ1,4ꢀdione (6). A solution
of compound 1 (0.5 g, 2.39 mmol) in THF (2 mL) was added to
a stirred solution of MeONa (3 mL) obtained from Na (0.11 g,
4.78 mmol) and MeOH (3 mL). The reaction mixture was stirred
for 1 h, then acidified with concentrated HCl to pH 2. The
solvents were evaporated, the mixture was diluted with brine
(5 mL) and extracted with EtOAc (3×5 mL). The combined
organic extracts were dried with MgSO4, the solvent was evapoꢀ
rated to obtain compound 6 in quantitative yield (0.35 g) as white
crystals, m.p. 96—98 °C. IR, ν/cm–1: 721, 769, 901, 935, 975,
1034, 1080, 1126, 1259, 1355, 1377, 1458, 1612, 1647, 1685,
1
1701, 1720, 3024, 3057, 3143, 3174. Major isomer. H NMR, δ:
4.30—4.63 (m, 4 H, OCH2CH2O); 7.07 (m, 1 H, H(1´)); 7.26
(d, 1 H, H(3´), J = 10.3 Hz); 7.38, 7.46 (both m, 3 H each,
H(2´), Ph). 13C NMR, δ: 66.92 (C(2), C(3)), 108.05 (C(5)),
121.63 (C(1´)), 127.77, 128.85, 129.86, 135.55 (Ph), 129.92
(C(8)), 134.97 (C(3´)), 136.41 (C(6)), 145.37 (C(2´)), 155.77
(C(9)), 182.54 (C(7)). Minor isomer. 1H NMR, δ: 4.30—4.63
(m, 4 H, OCH2CH2O); 7.05 (d, 1 H, H(1´), J = 10.5 Hz); 7.27
(d, 1 H, H(3´), J = 10.3 Hz); 7.38, 7.46 (both m, 3 H each,
H(2´), Ph). 13C NMR, δ: 66.99 (C(2), C(3)), 107.68 (C(5)),
123.27 (C(1´)), 127.52, 128.73, 129.65, 135.66 (Ph), 130.15
(C(8)), 136.41 (C(6)), 137.79 (C(3´)), 145.26 (C(2´)), 154.18
(C(9)), 182.77 (C(7)).
1
1751, 2852, 2922, 2953, 3392. H NMR, δ: 3.10 (s, 2 H, CH2);
5.30 (br.s, 1 H, OH). 13C NMR, δ: 41.14 (C(5)), 125.03 (C(2)),
165.19 (C(3)), 189.14, 192.18 (C(1), C(4)).
2ꢀChloroꢀ3ꢀmethoxycyclopentꢀ2ꢀenꢀ1,4ꢀdione (7). An etheꢀ
real solution of CH2N2 was added to a stirred solution of comꢀ
pound 6 (0.35 g, 2.39 mmol) in diethyl ether (10 mL) until evoluꢀ
tion of the gas stopped. The reaction mixture was stirred for
30 min, dried with MgSO4, the solvent was evaporated to obtain
compound 7 in quantitative yield (0.38 g) as beige crystals,
m.p. 110—112 °C. Found (%): C, 45.35; H, 3.53; Cl, 21.39.
C6H5ClO3. Calculated (%): C, 44.88; H, 3.14; Cl, 22.08. IR,
ν/cm–1: 613, 669, 690, 798, 869, 904, 927, 949, 968, 983, 1037,
(6E,Z)ꢀ8,9ꢀDichloroꢀ6ꢀ(1ꢀoxoꢀ3ꢀphenylpropꢀ2(E)ꢀenyl)ꢀ1,4ꢀ
dioxaspiro[4.4]nonꢀ8ꢀenꢀ7ꢀone (14) was obtained similarly to 13
from compound 1 (0.3 g, 1.43 mmol) and cinnamoyl chloride

842
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
Gimalova et al.
(0.24 g, 1.43 mmol). The yield was 0.1 g (~21%). Bright yellow
crystals, m.p. 180—182 °C. IR, ν/cm–1: 690, 791, 824, 953, 991,
1024, 1092, 1143, 1188, 1205, 1271, 1450, 1462, 1595, 1604,
1638, 1665, 1736, 3024, 3059, 3138, 3179. 1H NMR, δ: 2.89 (s, 1 H,
H(6)); 4.12, 4.28 (both m, 2 H each, OCH2CH2O); 6.45 (d, 1 H,
H(2´), J = 16.1 Hz); 7.39 (m, 3 H, Ph); 7.54 (d, 2 H, Ph, J = 6.2 Hz);
7.78 (d, 1 H, H(3´), J = 16.1 Hz). 13C NMR, δ: 46.84 (C(6)),
66.83 (OCH2CH2O), 108.74 (C(5), 117.29 (C(2´)), 128.96
(C(8)), 128.73, 129.34, 130.70, 134.10 (Ph), 146.99 (C(3´)),
158.80 (C(9)), 171.71 (C(1´)), 191.61 (C(7)).
crystals, m.p. 144—146 °C. MS, m/z: 376, 374 [MH]+. Major
isomer. 1H NMR, δ: 3.25 (t, 4 H, CH2N, J = 4.5 Hz, J = 4.7 Hz);
3.66 (t, 4 H, CH2O, J = 4.6 Hz, J = 4.8 Hz); 4.36 (s, 4 H,
OCH2CH2O); 6.71 (d, 1 H, H(1´), J = 15.9 Hz); 6.91 (d, 1 H,
H(3´), J = 11.5 Hz); 7.25—7.38 (m, 4 H, H(2´), oꢀPh, pꢀPh);
7.45 (d, 2 H, mꢀPh, J = 7.3 Hz). 13C NMR, δ: 48.49 (CH2N),
64.88 (CH2O), 66.34 (OCH2CH2O), 109.52 (C(5), 109.93
(C(8)), 123.99 (C(2´)), 127.12, 128.47, 128.70, 136.35 (Ph),
129.39 (C(3´)), 133.38 (C(6)), 140.49 (C(1´)), 156.20 (C(9)),
1
182.57 (C(7)). Minor isomer. H NMR, δ: 3.25 (t, 4 H, CH2N,
4ꢀChloroꢀ5ꢀhydroxyꢀ2(Z,E)ꢀ(3ꢀphenylpropꢀ2(E)ꢀenꢀ1ꢀyliꢀ
dene)cyclopentꢀ4ꢀenꢀ1,3ꢀdione (11) was obtained similarly to 6
from compound 13 (0.1 g, 0.31 mmol) and Na (0.014 g, 0.61 mmol)
in MeOH (3 mL) as a mixture of E/Zꢀisomers (in the ratio ~6 : 5
determined from the correlation of integral intensities of the
signals for the protons at C(2´) atom). The yield was 0.08 g
(~98%). Pale yellow crystals, m.p. 98—99 °C. IR, ν/cm–1: 721,
758, 783, 839, 983, 993, 1060, 1143, 1168, 1211, 1259, 1271,
1363, 1377, 1458, 1647, 1688, 1695, 2950, 3196. Major isomer.
1H NMR, δ: 7.24 (d, 1 H, H(1´), J = 11.79 Hz); 7.43 (m, 2 H,
J = 4.5 Hz, J = 4.7 Hz); 3.66 (t, 4 H, CH2O, J = 4.6 Hz,
J = 4.8 Hz); 4.36 (s, 4 H, OCH2CH2O); 6.34 (d, 1 H, H(1´),
J = 11.3 Hz); 6.84 (d, 1 H, H(3´), J = 11.7 Hz); 7.25—7.38 (m, 4 H,
H(2´), oꢀPh, pꢀPh); 7.45 (d, 2 H, mꢀPh, J = 7.3 Hz). 13C NMR,
δ: 48.72 (CH2N), 65.89 (CH2O), 66.34 (OCH2CH2O), 110.28
(C(5)), 110.80 (C(8)), 121.86 (C(2´)), 128.91 (C(3´)), 126.93,
128.47, 128.70, 136.12 (Ph), 133.50 (C(6)), 142.07 (C(1´)),
158.63 (C(9)), 183.09 (C(7)).
(6E,Z)ꢀ8,8´,9,9´ꢀTetrachloroꢀ6,7´ꢀbi(1,4ꢀdioxaspiro[4.4]ꢀ
nonane)ꢀ6(7´),8,8´ꢀtrienꢀ7ꢀones (16). A solution of BuLi in hexꢀ
ane (2.3 M, 1.14 mL, 2.63 mmol) was added dropwise under
argon to a solution of Pri2NH (0.37 mL, 2.63 mmol) in anhyꢀ
drous THF (10 mL) cooled to –10 °C. The reaction mixture was
stirred at this temperature for 15 min followed by a dropwise
addition of a solution of compound 1 (0.5 g, 2.39 mmol) in THF
(3 mL). After 15 min, the reaction mixture was cooled to –78 °C
and a solution of acetic anhydride (0.22 mL, 2.39 mmol) in THF
(6 mL) was added dropwise to it. The reaction mixture was stirred
for 1 h at –78 °C and 2 h at ~20 °C, diluted with saturated aq.
NH4Cl, (2—3 mL), and stirred for 10 min, THF was evaporated,
the residue was extracted with CHCl3. The combined organic
layers were washed with brine, dried with MgSO4, and concenꢀ
trated. The residue was purified by column chromatography on
silica gel (EtOAc—light petroleum, 1 : 4) to obtain compound 16
(0.12 g, ~45%) as colorless needleꢀlike crystals, m.p. 228—230 °C.
Found (%): C, 42.44; H, 2.33; Cl, 35.05. C14H10Cl4O5. Calcuꢀ
lated (%): C, 42.03; H, 2.52; Cl, 35.45. IR, ν/cm–1: 565, 856, 950,
989, 1035, 1058, 1170, 1201, 1460, 1616, 1635, 1718, 2953. MS,
m/z: 399, 401, 403 [MH]+. (Z)ꢀIsomer. 1H NMR, δ: 3.57 (s, 2 H,
CH2); 4.10, 4.23 (both m, 2 H each, OCH2CH2O); 4.46, 4.54
(both m, 2 H each, OCH2CH2O). 13C NMR, δ: 41.21 (CH2), 66.34,
66.61 (OCH2CH2O), 109.00 (C(5)), 110.64 (C(5´)), 127.83,
132.66 (C(8´), C(9´)), 137.39 (C(8)), 145.14 (C(6)), 149.42
(C(7´)), 154.21 (C(9)), 178.96 (C=O). (E)ꢀIsomer. 1H NMR, δ: 3.09
(s, 2 H, CH2); 4.07, 4.25 (both m, 2 H each, OCH2CH2O); 4.32,
4.51 (both t, 2 H each, OCH2CH2O, J = 7.10 Hz). 13C NMR, δ:
41.31 (CH2), 66.44, 67.02 (OCH2CH2O), 109.10 (C(5)), 110.75
(C(5´)), 124.94, 132.76 (C(8´), C(9´)), 137.52 (C(8)), 145.22,
149.51 (C(6), C(7´)), 154.28 (C(9)), 179.03 (C=O).
3
Ph); 7.65 (m, 4 H, H(3´), Ph); 8.19 (dd, H(2´), J = 15.72 Hz,
2J = 11.79 Hz). 13C NMR, δ: 124.14 (C(2´)), 125.81 (C(2)),
129.63, 130.62, 131.94, 137.37 (Ph), 136.41 (C(4)), 139.22 (C(3´),
150.22 (C(1´)), 165.68 (C(5)), 185.00 (C(1)), 187.54 (C(3)). Minor
1
isomer. H NMR, δ: 7.27 (d, 1 H, H(1´), J = 11.78 Hz); 7.43
(m, 4 H, Ph); 7.65 (m, 2 H, H(3´), Ph), 8.07 (dd, H(2´),
3J = 15.71 Hz, 2J = 11.78 Hz). 13C NMR, δ: 124.26 (C(2´)),
125.81 (C(2)), 129.63, 130.62, 131.94, 137.37 (Ph), 136.41
(C(4)), 139.22 (C(3´), 150.33 (C(1´)), 165.68 (C(5)), 185.00
(C(1)), 187.54 (C(3)).
4ꢀChloroꢀ5ꢀmethoxyꢀ2(Z,E)ꢀ(3ꢀphenylpropenꢀ2(E)ꢀylidene)ꢀ
cyclopentꢀ4ꢀenꢀ1,3ꢀdione (12) was obtained similarly to 7 by
methylation of compound 11 (0.08 g, 0.309 mmol) as a mixture
of Z/Eꢀisomers. The yield was 0.08 g (~94%). Bright yellow crysꢀ
tals, m.p. 229—231 °C. MS, m/z: 275 [MH]+, 259 [M – Me]+.
IR, ν/cm–1: 759, 837, 929, 1039, 1088, 1126, 1223, 1267, 1290,
1327, 1373, 1448, 1601, 1684, 1702, 1750, 2853, 2922, 2953,
3022, 3063, 3391. Major isomer. 1H NMR, δ: 4.39 (s, 3 H, OMe);
7.19 (m, 2 H, H(1´), H(3´)); 7.35 (m, 3 H, Ph); 7.56 (m, 2 H,
Ph), 8.10 (dd, H(2´), J = 15.0 Hz, J = 11.7 Hz). 13C NMR, δ:
60.21 (OMe), 122.98 (C(2´)), 127.28 (C(2)), 128.36, 128.93,
130.61, 135.37 (Ph), 133.40 (C(4)), 139.53 (C(3´)), 149.62
(C(1´)), 163.40 (C(5)), 183.76 (C(1)), 184.63 (C(3)). Minor isoꢀ
1
mer. H NMR, δ: 4.41 (s, 3 H, OMe); 7.19 (m, 2 H, H(1´),
H(3´)); 7.35 (m, 3 H, Ph); 7.56 (m, 2 H, Ph); 8.02 (dd, H(2´),
J = 15.7 Hz, J = 11.9 Hz). 13C NMR, δ: 60.21 (OMe), 122.68
(C(2´), 123.30 (C(2)), 128.36, 128.93, 130.61, 135.37 (Ph),
133.40 (C(4)), 139.74 (C(3´)), 149.90 (C(1´)), 163.10 (C(5)),
183.76 (C(1)), 184.14 (C(3)).
8ꢀChloroꢀ9ꢀmorpholinoꢀ6(E,Z)ꢀ(3ꢀphenylꢀ2(E)ꢀpropenꢀ1ꢀ
ylidene)ꢀ1,4ꢀdioxaspiro[4.4]nonꢀ8ꢀenꢀ7ꢀone (15). A solution of
morpholine (0.13 mL, 1.49 mmol) in MeOH (5 mL) was added
dropwise to a stirred solution of compound 13 (0.16 g, 0.49 mmol)
in MeOH (5 mL). The reaction mixture was stirred for 3 h at
~20 °C until complete conversion of the starting compound (TLC
monitoring). Methanol was evaporated, the residue was diluted
with cold H2O (10 mL) and extracted with CHCl3 (4×20 mL).
The combined extracts were washed with brine, dried with
MgSO4, the solvent was evaporated. The residue was purified by
column chromatography on silica gel (EtOAc—light petroleum,
1 : 4) to obtain compound 15 (0.12 g, ~65%) as clear pale yellow
This work was financially supported by the Russian
Foundation for Basic Research (Program RFBRꢀPoꢀ
volzh´e, Project No. 08ꢀ03ꢀ99012 r_ofi).
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Received May 27, 2008;
in revised form December 12, 2008