Photoinduced template synthesis of cyclobutane-containing crown ether

Article abstract of DOI:10.1007/s11172-008-0032-9

The photoinitiated [2+2]-cycloaddition of 1,5-bis[2-(3-phenyl-3-oxoprop-1- en-1-yl)phenoxy]-3-oxapentane in solution was studied. In the presence of potassium cations, the reaction is intramolecular and gives crown ether containing the γ-truxin-type cyclo

Full text of DOI:10.1007/s11172-008-0032-9

Russian Chemical Bulletin, International Edition, Vol. 57, No. 1, pp. 212—214, January, 2008
212
Photoinduced template synthesis of
cyclobutaneꢀcontaining crown ether

I. G. Ovchinnikova, O. V. Fedorova, P. A. Slepukhin, and G. L. Rusinov
I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22 ul. S. Kovalevskoi, 620219 Ekaterinburg, Russian Federation.
Fax: +7 (343 2) 74 1189. Eꢀmail: iov@ios.uran.ru
The photoinitiated [2+2]ꢀcycloaddition of 1,5ꢀbis[2ꢀ(3ꢀphenylꢀ3ꢀoxopropꢀ1ꢀenꢀ1ꢀyl)phenꢀ
oxy]ꢀ3ꢀoxapentane in solution was studied. In the presence of potassium cations, the reaction is
intramolecular and gives crown ether containing the γꢀtruxinꢀtype cyclobutane fragment (anti,
headꢀtoꢀhead) as the major product.
Key words: podands, chalcones, [2+2]ꢀcycloaddition, template synthesis, crown ethers.
Cyclobutaneꢀcontaining macrocyclic compounds are
respect to the oxyethylene fragment is characterized by
pronounced selectivity.5—7 The photoinduced [2+2]ꢀcyꢀ
cloaddition of cinnamic acid derivatives and chalcones in
solution generally affords mixtures of cyclobutaneꢀconꢀ
taining stereoisomers with αꢀ and εꢀtruxil and βꢀ and
γꢀtruxin structures.8 An analogous situation was observed
for podands containing cinnamic acid residues.9,10
of interest for supramolecular chemistry as ligands having
photocontrolled properties.1 Hence, the development of
new methods for the synthesis of such compounds is an
important problem. However, the stereoselectivity of periꢀ
cyclic reactions used for the synthesis of these comꢀ
pounds substantially depends on the degree of preꢀ
organization of the ethylene groups involved in the reacꢀ
tion.2 For example, the covalent preorganization of ethylꢀ
ene groups in chalconeꢀcontaining cyclophanes was used
for the synthesis of cyclobutaneꢀcontaining cyclophaꢀ
nes.3,4 The intramolecular photoinduced [2+2]ꢀcycloadꢀ
dition of acyclic analogs of crown ethers (podands) conꢀ
taining terminal ethylene groups in the para position with
With the aim of developing methods for the synthesis
of cyclobutaneꢀcontaining crown ethers, we examined
the tendency of orthoꢀsubstituted chalcone podand 1 preꢀ
pared from dialdehyde 2 to be involved in the photoinꢀ
duced [2+2]ꢀcycloaddition in solution (Scheme 1). The
irradiation of compound 1 for three weeks also gave an
1
inseparable mixture of products. The H NMR spectrum
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 204—206, January, 2008.
1066ꢀ5285/08/5701ꢀ0212 © 2008 Springer Science+Business Media, Inc.

Cyclobutaneꢀcontaining crown ether
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
213
O(1A)
C(7A)
somerism of the fourꢀmembered ring. All these signals can
be assigned to both the intramolecular and intermolecular
photoinduced [2+2]ꢀcycloaddition products. The low seꢀ
lectivity of the reaction can be attributed to the fact that
the Sꢀlike molecular geometry of chalcone podand 1 charꢀ
acterized by a large distance between the ethylene fragꢀ
ments of the terminal groups (ca. 8 Å, based on the Xꢀray
diffraction data) is, apparently, retained in solution (Fig.
1).
C(11A)
C(9A)
C(5A)
C(8A)
C(12A)
C(13A)
C(6A)
C(1A)
C(10A)
C(15A)
C(4A)
C(3A)
C(14A)
O(2A)
C(2A)
C(16A)
C(17A)
O(3)
We were the first to use a metal cation template to
preorganize the podand molecule for the intramolecular
photoinduced [2+2]ꢀcycloaddition (see Scheme 1). In
the presence of potassium cations, compound 1 underꢀ
goes the stereoselective intramolecular photoinduced
[2+2]ꢀcycloaddition due to the kinetic template effect to
give crown ether 3 containing the γꢀtruxinꢀtype cycloꢀ
butane fragment (as a racemic mixture of R,R,S,S and
C(17)
C(16)
C(2)
C(3)
C(4)
C(5)
O(2) C(15)
C(10)
C(14)
C(1)
C(7)
C(13)
C(12)
C(6)
O(1)
C(8)
C(9)
C(11)
1
S,S,R,R isomers). According to the H NMR spectrum,
Fig. 1. Molecular geometry of compound 1 in the crystal structure.
Selected bond lengths, d/Å: C(8)=C(9), 1.331(2); O(1)=C(7),
1.232(2); C(7)—C(8), 1.457(2); C(10)—C(9), 1.460(2); C(7)—C(6),
1.490(2).
the reaction mixture contains target product 3 (95%)
along with a small impurity (~5%) of the starting podand
1. It should be noted that no signals characteristic of the
stereoisomerism of the cyclobutane system of compound
3 were observed in the spectra of the reaction mixtures
measured in the absence of template ions. The singleꢀ
crystal Xꢀray diffraction study of compound 3 showed
that the latter was individual enantiomer 3a (Fig. 2).
of this mixture shows, along with the most intense signals
for the protons of the starting compound 1, several groups
of signals characteristic of cyclobutanes (δ 5.5—4.0), that
is, two sets of signals for the protons of the AA´BB´
multiplet system indicative of the headꢀtoꢀhead stereoꢀ
isomerism of the cyclobutane ring and two sets of signals
of the A2B2 multiplet system corresponding to the headꢀ
toꢀtail stereoisomerism of the cyclobutane ring.8 In addiꢀ
tion, the spectrum shows sets of triplets indicative of the
formation of compounds with the transꢀcisꢀcis stereoiꢀ
Experimental
The IR spectra were recorded on a Perkin—Elmer Spectrum
One Fourierꢀtransform spectrometer equipped with a diffuse reflecꢀ
C(4)
C(5)
C(6)
C(3)
C(8)
O(2)
C(9)
C(2)
C(1)
C(7)
C(10)
O(3)
C(11)
C(16)
O(1)
C(22)
C(33)
C(21)
C(34)
C(12)
C(13)
C(25)
C(14)
C(32)
C(31)
C(19)
C(29)
C(17)
O(5)
C(15)
C(26)
C(20)
O(4)
C(18)
C(27)
C(30)
C(24)
C(23)
C(28)
Fig. 2. Molecular geometry of enantiomer 3a in the crystal structure. Selected bond lengths, d/Å: C(21)—C(22), 1.567(2); C(21)—C(17),
1.570(2); C(19)—C(17), 1.528(2); C(19)—C(22), 1.573(2).

214
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
Ovchinnikova et al.
tance sampling accessory (DRA). The 1H NMR spectra were meaꢀ
sured on a Brukerꢀ400 instrument operating at 400 MHz in DMSOꢀ
d6 with SiMe4 as the internal standard. The EI mass spectra were
obtained on a Varian MAT 311ꢀA instrument; the ionizing electron
energy was 70 eV; the accelerating voltage was 3 kV. The melting
points were determined on a Boetius micro hotꢀstage apparatus.
The TLC analysis was carried out on Silufolꢀ254 plates using ethyl
acetate as the eluent. Spots were visualized by exposure to iodine
vapor.
1,5ꢀBis[2ꢀ(3ꢀphenylꢀ3ꢀoxopropꢀ1ꢀenꢀ1ꢀyl)phenoxy]ꢀ3ꢀ
oxapentane (1). Acetophenone (0.48 g, 4 mmol) was added to a
solution of formyl podand 2 (0.6 g, 2 mmol), which was prepared
according to a known procedure,11 in ethanol (50 mL). The reacꢀ
tion mixture was heated with magnetic stirring to 60—65 °C for 1 h.
Then a 20% NaOH solution (1 mL) was added as the catalyst, and
the mixture was gradually cooled with stirring for 3 h. The solution
together with the precipitate was kept in the dark at 3—5 °C for 12 h.
The crystals that formed were filtered off. The analytically pure
product was obtained by recrystallization from ethanol. The yield
was 0.78 g (80%), m.p. 109—110 °C. Found (%): C, 78.67; H, 5.75.
C34H30O5. Calculated (%): C, 78.76; H, 5.79. 1H NMR, δ: 3.96—
3.87 and 4.24—4.26 (both m, 8 H, Ar—O—CH2—CH2—O); 7.02
equipped with a CCD detector (MoꢀKα radiation, λ = 0.71073 Å,
graphite monochromator, T = 295 K). The structures were solved
by direct methods and refined by the fullꢀmatrix leastꢀsquares
method first with isotropic and then with anisotropic displacement
parameters for all nonhydrogen atoms based on F 2 with the use of
the SHELXSꢀ97 and SHELXLꢀ97 program packages. Hydrogen
atoms were partially located in difference electron density maps and
refined isotropically. The remaining hydrogen atoms were posiꢀ
tioned geometrically and refined using a riding model. The absorpꢀ
tion was ignored because of the small absorption coefficient
(µ = 0.085 cm–1). Compound 1. C34H30O5, M = 518.58, crystals
are monoclinic, space group C2/c, a = 15.738(4) Å, b = 11.889(2)
Å, c = 15.0830(15) Å, β = 105.47(14)°, V = 2720.0(9) Å3; Z = 4 (the
molecule occupies a special position on a twofold axis); 7115 meaꢀ
sured reflections (2.84 < θ < 31.63°), of which 2762 reflections are
independent (Rint = 0.0490), 1150 reflections are with I > 2σ(I),
ρ = 1.266 g cm–3, R factors based on all reflections are R1 = 0.0418,
wR2 = 0.0685, the final R factors (I > 2σ (I)) are R1 = 0.1172,
wR2 = 0.0759.
Compound 3a. C34H30O5, M = 518.58, crystals are monoꢀ
clinic, space group P2(1), a = 10.6087(4) Å, b = 9.8264(5) Å,
c = 13.1049(5) Å, β = 98.359(3)°, V = 1351.61(10) Å3; Z = 2; 9017
measured reflections (2.84 < θ < 31.63°), of which 4125 reflections
are independent (Rint = 0.0172), 2467 reflections are with
(I > 2σ(I)), ρ = 1.274 g cm–3, R factors based on all reflections are
R1 = 0.0669, wR2 = 0.0744, the final R factors (I > 2σ (I)) are
R1 = 0.0345, wR2 = 0.0694.
3
3
3
(dd, 2 H, Ar, J = 7.6 Hz, J = 7.3 Hz); 7.10 (d, 2 H, Ar, J =
8.4 Hz); 7.39 (ddd, 1 H, Ar, 3J = 8.4 Hz, 3J = 7.3 Hz, 4J = 1.6 Hz);
7.53 (t, 4 H, C(O)Ar´, 3J = 7.6 Hz); 7.61 (t, 2 H, C(O)Ar´, 3J =
7.3 Hz); 7.89 (dd, 2 H, Ar, 3J = 7.6 Hz, 4J = 1.6 Hz); 7.95 (d, 2 H,
—CH=CH—, 3J = 15.8 Hz); 8.01 (d, 2 H, —CH=CH—,
3J = 15.8 Hz); 8.07—8.11 (m, 4 H, C(O)Ar´). IR (DRA), ν/cm–1
:
This study was financially supported by the Russian
Foundation for Basic Research (Projects Nos 07ꢀ03ꢀ
96111, 06ꢀ03ꢀ08144, and 07ꢀ03ꢀ96113) and the Presidium
of the Russian Academy of Sciences (Project “Design of
New Supramolecular Structures Containing Heterocyclic
Fragments”).
784 (arom.); 1054, 1117, 1213, 1246 (ν , ν , CAr—O—CAlk
,
s
CAlk—O—CAlk); 1567, 1598 (C=C); 1650 (C=Oa)s; 2827, 2881, 2945
(CAlkH); 3001, 3058 (CAr—H).
16,17ꢀDibenzoylꢀ2,5,8ꢀtrioxatetracyclo[20.4.0.09,14
.
0
15,18]tricosaꢀ1(19),9,11,13,20,22ꢀhexaene (3), racemate. A
solution of compound 1 (0.05 g, 0.1 mmol) and KSCN (0.015 g,
0.1 mmol) in DMF (3 mL) was irradiated in a quartz cell (l =
10 mm) with unfiltered light from an incandescent lamp (λ > 280
nm) with power of 150 W located at a distance of 30 cm for 80 h (at
T = 20—25 °C) or with sunlight (on June) for one week. After
completion of the reaction, the mixture was transferred into a beaꢀ
ker, water was added, and the solid was filtered. The recrystallizaꢀ
tion from acetonitrile afforded colorless crystals of the analytically
pure sample. The yield was 0.047 g (95%), m.p. 218—220 °C.
Found (%): C, 78.79; H, 5.74. C34H30O5. Calculated (%): C,
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—
s
as
O—CAlk); 1580, 1597 (C=C); 1669, 1680 (C=O); 2889, 2919, 2945
(CAlk—H); 3013, 3058 (CAr—H).
Xꢀray diffraction study. Crystals of chalcone podand 1 were
grown by slow evaporation of a solution in acetonitrile; crystals of
cyclobutaneꢀcontaining crown ether 3, of a solution in DMF. The
single crystal under study were formed by the molecules of S,S,R,R
enantiomer (3a). The Xꢀray diffraction data for compounds 1 and
3a were collected on an automated Xcalibur 3 diffractometer
Received May 16, 2007;
in revised form October 12, 2007