Synthesis of dithiane-based photolabile molecular systems

Article abstract of DOI:10.1055/s-2001-15057

Synthesis of photolabile molecular systems based on lithiodithiane addition to carbonyl compounds is described. Dithianes of the spiro structure, e. g., 2,4,8,10-tetrathiaspiro[5.5]undecane and 2,4-dithia-8,10-dioxaspiro[5.5]undecane are utilized as tethers, thus allowing for a modular approach to building a diverse set of photocleavable molecules. A variety of carbonyl compounds ranging from simple substituted benzaldehydes to formylated benzocrown ethers, carbohydrates or calixarenes are found to be suitable for this chemistry.

Full text of DOI:10.1055/s-2001-15057

PAPER
1133
Synthesis of Dithiane-Based Photolabile Molecular Systems
D
ithiane-BasedPh
l
otolabi
e
le
M
olecul
g
ar Systems D. Mitkin, Yongqin Wan, Alexei N. Kurchan, Andrei G. Kutateladze*
Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80208–2436, USA
Fax +1(303)8712254; E-mail: akutatel@du.edu
Received 1 February 2001
Dedicated to Howard E. Zimmerman on the occasion of his 75th birthday
S
Abstract: Synthesis of photolabile molecular systems based on
OH
lithiodithiane addition to carbonyl compounds is described.
Li
CHO
S
S
Dithianes of the spiro structure, e.g., 2,4,8,10-tetrathiaspiro[5.5]un-
decane and 2,4-dithia-8,10-dioxaspiro[5.5]undecane are utilized as
tethers, thus allowing for a modular approach to building a diverse
set of photocleavable molecules. A variety of carbonyl compounds
ranging from simple substituted benzaldehydes to formylated ben-
zocrown ethers, carbohydrates or calixarenes are found to be suit-
able for this chemistry.
S
hν, ET-sens.
Scheme 1
many potential applications for these systems could be in
assembling photocleavable molecular hosts capable of re-
leasing guest molecules upon irradiation. Our specific
strategy was to tether two formylated macromolecular
blocks with spiro-bis-dithiane 1 (Scheme 2) or dithiane-
bis-methanol 2 (Scheme 3) to produce a photolabile sys-
tem equipped with one or two photocleavable C-C bonds.
Key words: photolabile molecular hosts, photoinduced electron
transfer, dithiane, 2,4,8,10-tetrathiaspiro[5.5]undecane, 2,4-dithia-
8,10-dioxaspiro[5.5]undecane, calix[4]arene, benzocrown ether, ri-
bofuranose, glucopyranose, galactopyranose
Recently we reported1 an efficient photoinduced C-C
bond cleavage in -hydroxyalkyl-1,3-dithianes (Corey–
Seebach dithiane-carbonyl adducts2). The mechanism of
this reaction involves photochemically induced single
electron transfer from the dithiane moiety to the excited
molecule of ET-photosensitizer (benzophenone), accom-
panied by mesolytic C-C cleavage in the generated cation-
radical, which is assisted by the anion-radical of ben-
zophenone.
A variety of compounds having a benzaldehyde fragment
in their structure are suitable for such assembly. In this pa-
per we report the synthesis of the linkers 1 and 2, ap-
proaches to several dithiane-bearing molecular building
blocks and, finally, joining these blocks together to fur-
nish photolabile molecular systems.
S
S
OH
OH
S
S
S
S
In view of the remarkable efficiency for both
lithiodithiane addition to substituted benzaldehydes and
photo-fragmentation of such dithiane adducts, we have
been investigating the applicability of these systems as
molecular latches that could be used to attach various mo-
lecular and macromolecular blocks and, at the same time,
could be selectively unfastened on demand.3 One of the
2
1
Figure 1
Synthesis of linkers 1 and 2: The novel spiro-bis-
BLOCK
A
LiO
S
BLOCK
A
HO
S
Li
S
S
S
S
S
S
S
S
BLOCK
A
BLOCK
B
CHO
CHO
S
S
Li
Li
BLOCK
B
OH
1(Li)
2
Scheme 2
dithiane 1 was synthesized starting from commercially
available pentaerythrityl tetrabromide (3). Nucleophilic
substitution by potassium thioacetate in DMF yielded
Synthesis 2001, No. 8, 18 06 2001. Article Identifier:
1437-210X,E;2001,0,08,1133,1142,ftx,en;C00801SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1134
O. D. Mitkin et al.
PAPER
BLOCK
B
CHO
HO
S
S
S
S
BLOCK
A
S
S
(1) BuLi
O
O
O
O
OH OH
(2)
BLOCK
B
BLOCK
A
CHO
2
BLOCK
A
Scheme 3
O
O
Br
Br
HO
HO
Br
Br
[CH2O]n/H+
-H2O
87% of the corresponding tetrathioacetate 4 (Scheme 4).
However, attempts to deacetylate 4 under basic conditions
(MeONa/MeOH) produced the target tetra-thiol that was
considerably contaminated by thietanes (Scheme 5). We
rationalized that intramolecular nucleophilic displace-
ment in this sterically hindered environment can be a sig-
nificant channel to partially relieve steric strain. An
alternative approach – combining both thioacetate hydrol-
ysis and thioacetal formation in one step under acid-cata-
lyzed conditions – was successful and the target spiro-bis-
dithiane 1 was obtained in 76% isolated yield.
5
6
HO
HO
S
S
O
O
SAc
SAc
H+/H2O
AcSK
DMF
7
2
Scheme 6
Symmetric photolabile bis-adducts based on 1: We first
exemplified our approach by generating bis-lithiated 1
and quenching it with excess benzaldehyde to produce
diol 8.4
Br
Br
Br
Br
AcS
AcS
SAc
SAc
AcSK
DMF
3
4
S
S
S
S
Ph
S
OH
S
CH2O
HCl
S
S
S
S
1
(1) 2 BuLi
Scheme 4
(2) PhCHO
S
S
Dimethanol 2 was synthesized from commercially avail-
able 2,2-bis(bromomethyl)-1,3-propanediol (5), which
was first protected via cyclic acetal formation with form-
aldehyde to give 6, and then reacted with potassium thio-
acetate. The critical feature of this synthetic sequence was
that during the next, acid-catalyzed step no extra formal-
dehyde was added and therefore the deprotection of the
diol and formation of the dithiane ring occurred via meth-
ylenic transfer from oxygens to sulfurs (59% yield).
1
Ph
OH
8
Scheme 7
More complex systems can be assembled using mono-
formylated calix[4]arene 95 as
building block
(R = EtOCH2CH2). Its reaction with dilithiated 1 in THF
furnished bis-calixarene 10 in 71% yield.
a
O
Bis-adducts 8 and 10 are photolabile molecular systems.
They cleave quantitatively, regenerating benzaldehyde or
calixarene 9 respectively, upon irradiation in the presence
of benzophenone in acetonitrile.
S
-OMe
S
S
S
O
S
Utilizing essentially the same conditions, we assembled
crown ether-based hosts 11 and 12, starting from mono-
formylated dibenzo-24-crown-8 and benzo-18-crown-6
ethers, respectively.
O
Scheme 5
Synthesis 2001, No. 8, 1133–1142 ISSN 0039-7881 © Thieme Stuttgart · New York

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Dithiane-Based Photolabile Molecular Systems
1135
CHO
OR
OR
HO
S
S
S
S
OR
RO
OR
Li
Li
S
S
S
OR
RO
OR
hν,
S
benzophenone
OR
RO
OR
OR
OH
9
10
Scheme 8
O
O
O
O
O
O
O
O
O
O
S
O
O
O
O
S
HO
OH
S
S
S
S
S
S
OH
HO
O
O
O
O
O
O
O
O
O
O
O
O
O
12
O
11
Figure 2
Complexation properties and photophysics of these and
other molecular hosts described in this paper will be dis-
cussed elsewhere.
S
S
S
S
S
S
O
O
Monoadducts as building blocks for non-symmetric
assemblies: In order to diversify the series of photocleav-
able molecular hosts containing our dithiane-based photo-
latching device, we synthesized a series of mono-adducts
of 1 and monoacetals of 2, which were utilized in the sub-
sequent steps for coupling with various formyl-bearing
blocks:
BLOCK
A
OH
BLOCK
A
Figure 3
Thus, on reacting formyl-substituted benzocrown ethers
or calix[4]arene with mono-lithiated spiro-bis-dithiane 1,
we synthesized 13–16.
Similar monodithiane-containing systems can be readily
obtained from diol 2 via acetal formation. The simplest il-
lustration of this approach is the benzaldehyde acetal 20,
which upon treatment with butyl lithium and quenching
with another mole of benzaldehyde produces photocleav-
able molecule 21.
Bidentate precursors 17–19 were prepared from mono-
lithiated
1
and bis-formylated dibenzocrowns6 or
calix[4]arene.5
Synthesis 2001, No. 8, 1133–1142 ISSN 0039-7881 © Thieme Stuttgart · New York

1136
O. D. Mitkin et al.
PAPER
S
S
OH
S
S
S
S
S
S
S
(1) BuLi
PhCHO/H+
OHC
S
OH OH
O
2
O
O
O
(2) PhCHO
O
O
HO
OH
OMe
O
O
O
O
O
2
OMe
O
22
23
20
21
Scheme 10
Scheme 9
lyzed conditions furnished acetal 23 in 72% yield
(Scheme 10). A similar synthetic sequence starting from
D-galactose derivative 24 produced a D-galactopyranosyl-
bearing dithiane 25, although the overall yield was only
38% (Scheme 11).
We utilized this coupling mode in order to introduce
chiral auxiliary groups into the building blocks, specifi-
cally, in conjunction with carbohydrate-based formylated
systems. There are several readily available formyl-bear-
ing pyranoses or furanoses, with fully protected hydroxy
groups, which are suitable for Corey–Seebach chemistry.
For example, treating furanose 22 with 2 under acid-cata-
S
S
S
S
S
S
S
S
S
S
S
S
S
S
OR
RO
OR
S
S
OH
O
OR
OH
O
HO
O
OH
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
13
O
16
14
15
Figure 4
S
S
S
S
S
S
S
S
HO
S
S
S
S
HO
HO
O
O
O
O
O
O
O
OR
O
O
OR RO
OR
O
O
O
O
O
OH
S
S
OH
S
OH
S
S
S
S
S
S
S
S
S
17
19
18
Figure 5
Synthesis 2001, No. 8, 1133–1142 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Dithiane-Based Photolabile Molecular Systems
1137
the photolabile (hybrid) systems that were synthesized by
joining dissimilar dithiane and formyl-bearing compo-
nents.
S
S
S
S
CHO
Details on experimental procedures can be found in the
experimental section.
OH OH
O
O
2
O
O
O
O
O
In conclusion, we have shown that the classic dithiane-
carbonyl chemistry can be successfully adopted to assem-
ble a diverse set of organic macromolecules, which are ca-
pable of photochemically induced disassembly in the
presence of electron-transfer sensitizers.
O
O
O
O
O
24
25
Scheme 11
Common reagents were purchased from Aldrich Chemical Co. and
used without additional purification. THF was refluxed over and
distilled from potassium benzophenone ketyl prior to use. H and
1
Glycosidation of phenols bearing formyl or dithiane moi-
eties offered yet another approach to chiral building
blocks. We coupled tetramethyl glucopyranose 26 with
5-(p-hydroxyphenyl)-1,3-dithiane 277 to furnish dithiane-
bearing permethylated glucopyranoside 28.
13C NMR spectra were recorded at 25 °C on a Varian Mercury 400
MHz instrument. TMS was used as an internal standard. Column
chromatography was performed on silica gel, 70–230 mesh ASTM,
using EtOAc–hexane mixtures (gradient from 1:20 to 1:2), unless
specified. HP 6890 with MSD detector was used to analyze the
compounds.
S
5,5-Bis(bromomethyl)-[1,3]dioxane (6)8
OMe
HO
To a solution of 2,2-bis(bromomethyl)-1,3-propanediol (5, 5 g, 19.1
mmol) in formalin (7.0 mL) was added concd HCl (4 mL) at r.t. The
mixture was refluxed overnight with stirring. After being cooled to
r.t., it was extracted twice with CH2Cl2 (2 15 mL). The organic
phases were combined and washed with sat. Na2CO3 (30 mL), dried
(MgSO4), and solvent was then removed under reduced pressure to
afford the crude acetal 6 (5.0 g, 96%). It was used without further
purification.
S
O
27
MeO
MeO
OH
OMe
Ph3P, DEAD
26
OMe
1H NMR (CDCl3): = 4.79 (s, 2H), 3.83 (s, 4H), 3.58 (s, 4H).
13C NMR (CDCl3): = 94.4, 71.5, 38.1, 35.2.
MS (EI): m/z (%) = 273 (M+, 5), 244 (15), 214 (90), 163 (50), 133
S
S
O
MeO
MeO
O
OMe
(60), 53 (100).
28
Pentaerythrityl tetrathioacetate (4)
Scheme 12
Potassium thioacetate (31.8 g, 278 mmol) was dissolved in DMF
(150 mL) and pentaerythrityl tetrabromide (3, 12.1 g, 31 mmol) was
added to this solution. The reaction mixture was stirred under N2
atm for 60 h at 25 °C, the solvent was then removed under vacuum.
The residue was dissolved in CH2Cl2 (150 mL) and washed thrice
with H2O (3 100 mL). The organic phase was dried (MgSO4) and
concentrated. The crude product was recrystallized from MeOH to
give the title compound (10.1 g, 87%).
Various carbohydrate fragments can also be introduced in
the form of glycosides of p-hydroxybenzaldehyde. For ex-
ample, glycosidation with tetraacetylated glucopyranosyl
bromide produced 29, which we utilized as a carbonyl
component.
1H NMR (CDCl3): = 3.04 (s, 8H), 2.36 (s, 12H)
13C NMR (CDCl3): = 194.0, 42.7, 34.9, 30.7.
MS (EI): m/z (%) = 325 ([M – CH3CO]+,100), 283 (40), 241 (90),
OAc
O
223 (45), 119 (30).
CHO
AcO
AcO
O
5,5-Bis(acetylthiomethyl)-[1,3]dioxane (7)
OAc
29
Potassium thioacetate (6.25 g, 54.7 mmol) was dissolved in DMF
(40 mL) and 5,5-bis(bromomethyl)-[1,3]dioxane (6, 5.0 g, 18.3
mmol) was added to this solution. The reaction mixture was stirred
for one day at r.t. The solvent was removed under vacuum. The res-
idue was dissolved in CH2Cl2 (50 mL), washed with H2O (50 mL),
brine (50 mL), and dried (MgSO4). The organic layer was concen-
trated to afford the crude product 7 (4.0 g, 82%). It was used with-
out further purification.
1H NMR (CDCl3): = 4.78 (s, 2H), 3.66 (s, 4H), 3.09 (s, 4H), 2.36
(s, 6H).
13C NMR (CDCl3): = 194.4, 94.1, 72.5, 37.7, 31.4, 30.7.
Figure 6
Building a diverse series of photolabile molecular ob-
jects: Having such a diverse assortment of precursors, we
then coupled them with aromatic aldehydes, ranging in
complexity from unpretentious benzaldehyde, to formy-
lated benzocrown ethers, to calixarenes. Figure 7 shows
Synthesis 2001, No. 8, 1133–1142 ISSN 0039-7881 © Thieme Stuttgart · New York

1138
O. D. Mitkin et al.
PAPER
Ph
HO
OMe
OAc
S
S
S
Ph
S
S
S
O
O
MeO
MeO
O
AcO
AcO
O
OH
OH
O
OMe
OAc
O
30
O
O
32
OMe
O
OH
O
O
O
O
S
S
OR
RO
OR
31
OH
O
O
S
OR
S
OH
S
S
O
O
O
O
O
OR
RO
OR
S
S
OR
S
O
S
HO
S
S
OR
RO
OR
35
HO
OR
HO
33
OH
O
O
O
S
S
O
O
S
O
OR
RO
OR
O
OH
S
OH
OR
OR
RO
OR
O
O
O
S
OR
S
S
O
O
S
HO
S
O
O
S
S
O
S
OR
RO
OR
36
O
OR
HO
HO
34
Figure 7 Photolabile hybrids assembled by coupling different dithiane- and formyl-bearing building blocks
MS (EI): m/z (%) = 264 (M+, 2), 221 (100), 191 (10), 179 (10), 131
(15), 117 (20), 99 (14), 85 (22).
crude product 2 (0.40 g, 59%). Recrystallization from CH2Cl2 af-
forded pure compound as white crystals, mp 100.5–101 °C.
1H NMR (CDCl3): = 3.90 (s, 4H), 3.77 (s, 1H), 3.69 (s, 2H), 2.96
(s, 1H), 2.72 (s, 4H).
13C NMR (CDCl3): = 67.6, 67.3, 44.4, 34.6, 33.4, 32.1.
MS (EI): m/z (%) = 180 (M+, 95), 115 (30), 85 (100), 71 (45), 57
(60).
2,4,8,10-Tetrathiaspiro[5.5]undecane (1)
Pentaerythrityl tetrathioacetate (4, 3 g, 8.15 mmol) was suspended
in a formalin–HCl mixture (53 mL of 40% formalin, 8 mL of 37%
HCl) and the reaction mixture was refluxed for 16 h. It was neutral-
ized with sat. Na2CO3 after being cooled to r.t. The product was ex-
tracted with CH2Cl2 (50 mL), the organic layer was dried (MgSO4),
and concentrated. Crude product was recrystallized from a CHCl3–
MeOH mixture. Decolorization when boiling with activated carbon
in CHCl3–MeOH (70:30) for 1 h gave white crystals 1 (1.39 g,
76%), mp 163–164 °C.
1H NMR (CDCl3): = 3.66 (s, 4H), 2.95 (s, 8H).
13C NMR (CDCl3): = 38.6, 32.2, 24.9.
MS (EI): m/z (%) = 224 (M+,100), 177 (30), 131 (40), 99 (60), 85
Anal. Calcd for C6H12O2S2: C, 39.97; H, 6.71. Found: C, 39.72; H,
6.77.
Acetal Preparation with 2:3-Phenyl-2,4-dioxa-8,10-dithia-
spiro[5.5]undecane (20); Typical Procedure
To a solution of benzaldehyde (106 mg, 1.0 mmol) and 5,5-bis-(hy-
droxymethyl)-[1,3]dithiane (2, 180 mg, 1.0 mmol) in benzene (20
mL) was added toluene sulfonic acid monohydrate (20 mg). H2O
was removed by azeotrope formation during 3 h. The reaction mix-
ture was cooled to r.t. and washed with sat. NaHCO3 (20 mL). The
aqueous layer was extracted twice with benzene (2 20 mL), the or-
ganic phases were combined, dried (MgSO4), and concentrated to
give 20 (256 mg, 96%).
(50).
Anal. Calcd for C7H12S4: C, 37.46; H, 5.39. Found: C, 37.28; H,
5.53.
5,5-Bis(hydroxymethyl)-[1,3]dithiane (2)
1H NMR (CDCl3): = 7.50–7.44 (m, 2H), 7.40–7.32 (m, 3H), 5.43
(s, 1H), 4.53 (d, 2H, J = 12 Hz), 3.70 (s, 2H), 3.66 (d, 2H, J = 12
Hz), 3.16 (s, 2H), 2.50 (s, 2H).
13C NMR (CDCl3): = 137.6, 128.9, 128.2, 125.9, 102.3, 73.9,
34.7, 34.6, 32.4, 28.4.
To a solution of 2 N HCl (20 mL) was added dithioacetate (7, 1 g,
3.8 mmol), and the reaction mixture was refluxed for one day. The
dark oil residue was discarded. The reaction mixture was cooled,
neutralized with Na2CO3, then extracted with CH2Cl2 (4 30 mL).
The organic layer was dried (MgSO4), and concentrated to give
MS (EI): m/z (%) = 268 (M+, 100), 132 (50), 99 (55), 85 (55).
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PAPER
Dithiane-Based Photolabile Molecular Systems
1139
3-(6-Methoxy-2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-
yl)-2,4-dioxa-8,10-dithiaspiro[5.5]undecane (23)
Methyl 2,3-O-isopropylidene-5-aldehydo- -D-ribofuranoside9 (22,
500 mg, 2.5 mmol), 2 (490 mg, 2.7 mmol) and TsOH H2O (30 mg)
in benzene were reacted, as described above for 20, to give 646 mg
(72%) of 23.
1H NMR (CDCl3): = 5.00 (s, 1H), 4.80 (d, 1H, J = 5 Hz), 4.53 (d,
1H, J = 5 Hz), 4.45 (d, 2H, J = 12 Hz), 4.37 (d, 1H, J = 8 Hz), 4.11
(d, 1H, J = 8 Hz), 3.67 (s, 2H), 3.42 (d, 2H, J = 12 Hz), 3.34 (s,
3H), 3.05 (s, 2H), 2.42 (s, 2H), 1.48 (s, 3H), 1.32 (s, 3H).
13C NMR (CDCl3): = 139.8, 137.5, 129.0, 128.4, 128.21, 128.18,
126.6, 125.9, 102.3, 74.7, 74.2, 73.0, 53.3, 33.1, 32.0, 28.5.
HRMS: m/z calcd for C20H23O3S2 [MH+] 375.1089. Found:
375.1096.
[9-(Hydroxy-phenyl-methyl)-2,4,8,10-tetrathia-
spiro[5.5]undec-3-yl]-phenyl-methanol (8)
2,4,8,10-Tetrathiaspiro[5,5]undecane (1, 64 mg, 0.30 mmol), BuLi
(0.86 mmol) and benzaldehyde (91 mg, 0.86 mmol) were reacted as
described above for 21. Column chromatography yielded 8 as a
mixture of diastereomers (78 mg, 63%):
1H NMR (CDCl3): = 7.42–7.28 (m, 10H), 4.88–4.81 (m, 2H),
4.03–3.96 (m, 2H), 3.12–2.62 (m, 10H).
13C NMR (CDCl3): = 112.5, 108.9, 101.2, 86.8, 84.7, 80.9, 73.3,
73.2, 54.7, 34.5, 34.4, 32.3, 28.5, 26.5, 25.2.
HRMS: m/z calcd for C15H25O6S2 [MH+]: 365.1093. Found:
365.1100.
13C NMR (CDCl3): = 139.7, 128.4, 128.2, 126.63, 126.60, 74.5,
74.4, 53.0, 52.8, 52.7, 36.9, 36.8, 36.3, 36.0, 35.9, 35.2, 35.0, 25.3.
5-(2,4-Dioxa-8,10-dithiaspiro[5.5]undec-3-yl)-2,2,7,7-
HRMS: m/z calcd for C21H25O2S4 [MH+]: 437.0737. Found:
437.0695.
tetramethyl-tetrahydro-bis[1,3]dioxolo[4,5-b;4’,5’-d]pyran (25)
1,2:3,4-Di-O-isopropylidene-6-aldehydo- -D-galactopyranose9,10
(24, 997 mg, 3.8 mmol), 2 (759 mg, 4.7 mmol) and TsOHH2O (40
mg) in benzene were reacted as described above and purified by col-
umn chromatrography (silica gel; EtOAc–hexane) (620 mg, 38%).
1H NMR (CDCl3): = 5.56 (d, 1H, J = 5 Hz), 4.66 (d, 1H, J = 7
Hz), 4.60 (dd, 1H, J = 12, 2 Hz), 4.58 (dd, 1H, J = 8, 2 Hz), 4.37
(dd, 1H, J = 12, 2 Hz) 4.29 (dd, 1H, J = 5, 2 Hz), 4.27 (dd, 1H,
J = 12, 2 Hz), 3.76–3.74 (m, 2H), 3.67 (d, 1H, J = 14 Hz), 3.49 (dd,
2H, J = 12, 8 Hz), 3.13 (d, 1H, J = 14 Hz), 2.96 (d, 1H, J = 14 Hz),
2.48 (d, 1H, J = 14 Hz), 2.37 (d, 1H, J = 14 Hz), 1.54 (s, 3H), 1.46
(s, 3H), 1.35(s, 3H), 1.32 (s, 3H).
Calixarenic Bis-adduct (10)
A solution of 2,4,8,10-tetrathiaspiro[5.5]undecane (1, 50 mg, 0.22
mmol) in THF (10 mL) was cooled to –78 °C under N2. Then n-
BuLi (1.6 M solution in hexanes, 0.80 mmol, 0.50 mL) was added
drop-wise with stirring. The resulting mixture was stirred for 2 h at
–25 °C and reacted as described above for 21 with 5-formyl-
25,26,27,28-tetrakis(2-ethoxyethoxy)calix[4]-arene5 (9, 330 mg,
0.45 mmol). After column separation, the title compound was ob-
tained (270 mg, 71%).
1H NMR (CDCl3): = 6.70–6.42 (m, 22H), 4.52–4.39 (m, 10H),
4.18–4.04 (m, 16H), 3.93–3.87 (m, 2H), 3.86–3.80 (m, 16H), 3.57–
3.49 (m, 16H), 3.18–3.06 (m, 10H), 2.90–2.57 (m, 6H), 2.02–1.92
(m, 2H), 1.25–1.15 (m, 24H).
13C NMR (CDCl3): = 109.2, 108.7, 100.0, 96.3, 74.0, 72.7, 70.6,
70.5, 70.3, 68.8, 34.6, 34.5, 32.4, 28.6, 26.3, 26.1, 25.0, 24.6.
HRMS: m/z calcd for C18H29O7S2 [MH+]: 421.1355. Found:
421.12998.
HRMS: m/z calcd for C97H123O17S4 [MH – H2O]+: 1687.7640.
Found: 1687.7696.
Dithiane–Carbonyl Adducts: Phenyl-(3-phenyl-2,4-dioxa-8,10-
dithiaspiro[5.5]undeca-9-yl)methanol (21); Typical Procedure
A solution of 3-phenyl-2,4-dioxa-8,10-dithia-spiro[5.5]undecane
(20, 244 mg, 0.91 mmol) in freshly distilled THF (10 mL) was
cooled to –25 °C under N2. Then n-BuLi (1.6 M solution in hex-
anes, 1.46 mmol, 0.91 mL) was added drop-wise with stirring. The
resulting mixture was stirred for 2 h at –25 °C to complete lithia-
tion. The resulting solution of the anion was cooled to –78 °C, and
a solution of benzaldehyde (155 mg, 1.46 mmol) in THF (2 mL) was
added drop-wise with stirring. The reaction mixture was stirred for
1 h at this temperature and then stored in a freezer at –25 °C over-
night. It was quenched with a sat. NH4Cl, extracted twice with Et2O
Mono-adduct of 1 with Calixarene; Compound 13
A solution of 1 (430 mg, 1.92 mmol) in THF (20 mL) was treated
with n-BuLi (1.6 M solution in hexanes, 1.92 mmol, 1.20 mL) and
reacted with 5-formyl-25,26,27,28-tetrakis(2-ethoxyethoxy)cal-
ix[4]arene (370 mg, 0.5 mmol) as described above for 21. After col-
umn separation, the title compound was obtained (416 mg, 86%).
1H NMR (CDCl3): = 6.70–6.48 (m, 11H), 4.53–4.43 (m, 5H),
4.17–4.05 (m, 8H), 3.94 (d, 1H, J = 7 Hz), 3.86–3.81 (m, 8H), 3.64
(s, 2H), 3.58–3.51 (m, 8H), 3.18–2.66 (m, 12H), 2.02 (s, 1H), 1.25–
1.16 (m, 12H).
Anal. Calcd for C52H68O9S4: C, 64.70; H, 7.10. Found: C, 64.83; H,
7.24.
(2
10 mL), and the combined organic extracts were dried
(MgSO4). The solvent was then removed under reduced pressure.
The residue was purified on a silica gel column (EtOAc–hexane) to
give two pairs of diastereomers (270 mg, 79%).
Mono-adduct of 1 with 4-formyldibenzo-18-crown-6;
Compound 14
A solution of 1 (462 mg, 2.06 mmol) in THF (50 mL) was treated
with n-BuLi (1.6 M solution in hexanes, 6.19 mmol, 3.87 mL), and
reacted with 4-formyldibenzo-18-crown-611 (370 mg, 0.5 mmol) as
described above for 21. After column separation (silica gel; CHCl3–
MeOH; 19:1), the title compound was obtained (512 mg, 81%).
1H NMR (CDCl3): = 6.96–6.78 (m, 7H), 4.77 (d, 1H, J = 7 Hz),
4.24–4.12 (m, 8H), 4.06–3.96 (m, 9H), 3.62 (s, 2H), 3.26–2.64 (m,
9H).
Diastereomers 21a
1H NMR (CDCl3): = 7.50–7.30 (m, 10H), 5.40 (s, 1H), 4.86 (dd,
1H, J = 3, 8 Hz), 4.51 (dd, 1H, J = 3, 11 Hz), 4.36 (dd, 1H, J = 3,
11 Hz), 4.03 (d, 1H, J = 8 Hz), 3.65 (d, 1H, J = 11 Hz), 3.63 (d, 1H,
J = 11 Hz), 3.29 (d, 1H, J = 14 Hz), 3.02 (d, 1H, J = 14 Hz), 3.02
(d, 1H, J = 3 Hz), 2.50 (d, 1H, J = 14 Hz), 2.38 (d, 1H, J = 14 Hz).
13C NMR (CDCl3): = 139.7, 137.5, 128.9, 128.4, 128.19, 128.18,
126.7, 125.9, 102.2, 74.4, 73.6, 52.9, 32.5, 31.9, 28.5.
13C NMR (CDCl3): = 148.61, 148.57, 148.4, 132.8, 121.2, 119.6,
113.6, 112.7, 111.8, 74.5, 70.0, 69.9, 68.9, 68.8, 53.4, 38.8, 37.5,
37.1, 36.1, 32.0, 25.2.
HRMS: m/z calcd for C28H35O6S4 [MH – H2O]+: 595.1317. Found:
595.1289.
Diastereomers 21b
1H NMR (CDCl3): = 7.50–7.30 (m, 10H), 5.40 (s, 1H), 4.91 (dd,
1H, J = 3, 7 Hz), 4.56 (dd, 1H, J = 3, 12 Hz), 4.32 (dd, 1H, J = 3,
12 Hz), 4.08 (d, 1H, J = 7 Hz), 3.70 (d, 1H, J = 12 Hz), 3.63 (d, 1H,
J = 12 Hz), 3.31 (d, 1H, J = 14 Hz), 2.99 (d, 1H, J = 14 Hz), 2.88
(d, 1H, J = 3 Hz), 2.58 (d, 1H, J = 14 Hz), 2.37 (d, 1H, J = 14 Hz).
Synthesis 2001, No. 8, 1133–1142 ISSN 0039-7881 © Thieme Stuttgart · New York

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PAPER
2-(4-[1,3]Dithian-5-yl-phenoxy)-6-methoxymethyl-3,4,5-
Bidentate Precursor 19; Typical Procedure
A solution of 1 (1.2 g, 5.35 mmol) in freshly distilled THF (20 mL)
was cooled to –78 °C under N2. Then n-BuLi (1.6 M solution in
hexanes, 5.76 mmol, 3.6 mL) was added drop-wise with stirring.
The resulting mixture was allowed to stand for 2 h at –20 °C. Then
5,17-diformyl-25,26,27,28-tetrakis(2-ethoxyethoxy)calix[4]arene5
(0.62 g, 0.8 mmol) was added and the reaction mixture was stirred
overnight at r.t. The reaction mixture was quenched with sat.
NH4Cl, evaporated, and extracted with CHCl3. The solvent was re-
moved under reduced pressure and the residue was purified by col-
umn chromatography (EtOAc–hexane, 2:3) to afford 0.484 g of 19
(49.7%).
trimethoxy-tetrahydropyran (28)
To a stirred solution of 2,3,4,6-tetra-O-methyl-D-glucopyranose
2612 (400 mg, 1.69 mmol) and 4-[1,3]dithian-5-yl-phenol (27, 358
mg, 1.69 mmol) in THF (6 mL) at 0 °C were added Ph3P (443mg,
1.69 mmol) and a solution of diethyl azodicarboxylate (294 mg,
1.69 mmol) in THF (3 mL). The mixture was stirred at r.t. over-
night. It was concentrated and the product was isolated by column
chromatography to afford 28 (510 mg, 70%).
1H NMR (CDCl3): = 7.09 (d, 2H, J = 8 Hz), 6.97 (d, 2H, J = 8
Hz), 4.80 (d, 1H, J = 7 Hz), 4.09 (d, 1H, J = 14 Hz), 3.67–3.64 (m,
1H), 3.65 (s, 3H), 3.64 (s, 3H), 3.59–3.55 (m, 1H), 3.55 (s, 3H),
3.49–3.39 (m, 2H), 3.38 (s, 3H), 3.30–3.20 (m, 3H), 3.16–3.08 (m,
1H), 3.05–2.95 (m, 2H), 2.82–2.75 (m, 2H).
Calixarenic Bidentate Precursor 19
1H NMR (CDCl3) = 6.29–6.86 (m, 10H), 4.46–4.52 (m, 4H),
4.34–4.39 (m, 2H), 4.18–4.21 (m, 4H), 4.00–4.07 (m, 4H), 3.78–
3.89 (m, 10H), 3.63 (s, 2H), 3.49–3.58 (m, 8H), 2.67–3.17 (m,
20H), 2.04 (s, 2H), 1.14–1.23 (m, 12H).
13C NMR (CDCl3): = 156.1, 139.2, 127.4, 116.8, 101.2, 86.2,
83.3, 79.0, 74.7, 71.1, 60.9, 60.5, 60.4, 59.3, 43.1. 35.9, 35.8, 31.1.
Adduct of 28 with Benzaldehyde; Compound 30
Anal. Calcd for C60H80O10S8: C, 59.18; H, 6.62. Found: C, 58.77; H,
6.84.
A solution of glycoside 28 (190 mg, 0.44 mmol), n-BuLi (1.6 M so-
lution in hexanes, 0.71 mmol, 0.44 mL), and benzaldehyde (75 mg,
0.71 mmol) was reacted as described above for 21. The product was
purified by column chromatrography. (76 mg, 32%).
1H NMR (CDCl3): = 7.46–7.32 (m, 5H), 7.07 (d, 2H, J = 8 Hz),
6.95 (d, 2H, J = 8 Hz), 4.91 (dd, 1H, J = 4, 7 Hz), 4.77 (d, 1H,
J = 6 Hz), 4.48 (d, 1H, J = 6 Hz), 3.65–3.63 (m, 1H), 3.64 (s, 3H),
3.63 (s, 3H), 3.58–3.54 (m, 1H), 3.54 (s, 3H), 3.40–3.37 (m, 1H),
3.37 (s, 3H), 3.28–3.18 (m, 3H), 3.07–2.94 (m, 3H), 2.90–2.80 (m,
2H), 2.72 (d, 1H, J = 4 Hz).
Dibenzo-24-crown-8 based Bidentate Precursor 18
1H NMR (CDCl3) = 6.79–6.96 (m, 6H), 4.74–4.79 (m, 2H), 4.11–
4.28 (m, 8H), 4.00 (d, 2H, J = 7.3 Hz), 3.86–3.90 (m, 8H), 3.79–
3.82 (m, 8H), 3.64 (s, 4H), 2.73–3.09 (m, 16H), 2.00 (s, 2H).
Dibenzo-18-crown-6 based Bidentate Precursor 17
1H NMR (DMSO-d6) = 6.82–6.95 (m, 6H), 4.63 (d, 2H), 4.18 (d,
2H), 4.01–4.07 (m, 8H), 3.79–3.85 (m, 8H), 3.70 (s, 4H), 2.67–3.10
(m, 16H).
13C NMR (CDCl3): = 156.2, 139.9, 138.4, 128.4, 128.2, 127.5,
126.3, 116.9, 101.3, 86.3, 83.4, 79.1, 75.8, 74.8, 71.2, 60.9, 60.6,
60.5, 59.4, 54.9, 42.6, 36.6, 36.2.
Adduct of 23 with Benzaldehyde; Compound 31
A solution of 23 (287 mg, 0.79 mmol), n-BuLi (1.6 M solution in
hexanes, 1.3 mmol, 0.79 mL), and benzaldehyde (134 mg, 1.3
mmol) was reacted as described above for 21. Purification by col-
umn chromatography produced diastereomers 31 (160 mg, 43%).
HRMS: m/z calcd for C27H35O6S2 [MH – H2O]+: 519.1875. Found:
519.1856.
Adduct of 29 with Dithiane; Compound 32
A solution of 1,3-dithiane (100 mg, 0.83 mmol) in THF (15 mL)
was cooled to –25 °C under N2. Then n-BuLi (1.6 M solution in
hexanes, 1.0 mmol, 0.63 mL) was added drop-wise with stirring.
The resulting mixture was stirred for 2 h at –25 °C. It was then add-
ed slowly into a solution of 4-O-[tetra-O-acetyl- -D-glucopyrano-
syl]benzaldehyde 2913 (377 mg, 0.83 mmol) in THF (20 mL) at
–78 °C with vigorous stirring. The reaction mixture was stirred for
1 h at this temperature and then stored in a freezer at –25 °C over-
night. The work-up procedure was the same as for 21. The product
was purified by column chromatography (250 mg, 52%).
1H NMR (CDCl3): = 7.35 (d, 2H, J = 9 Hz), 6.98 (d, 2H, J = 9
Hz), 5.32–5.23 (m, 2H), 5.16 (m, 1H), 5.09 (dd, 1H, J = 3, 6 Hz),
4.88 (d, 1H, J = 6 Hz), 4.27 (dd, 1H, J = 6, 12 Hz), 4.16 (d, 1H,
J = 12 Hz), 4.04 (dd, 1H, J = 3, 8 Hz), 3.89–3.82 (m, 1H), 3.02–
2.88 (m, 2H), 2.78–2.68 (m, 2H), 2.05–1.95 (m, 2H), 2.08 (s, 3H),
2.051 (s, 3H), 2.046 (s, 3H), 2.03 (s, 3H).
Diastereomers 31a
1H NMR (CDCl3): = 7.41–7.29 (m, 5H), 5.00 and 4.99 (two s,
1H), 4.86 (dd, 1H, J = 3, 8 Hz), 4.78 (d, 1H, J = 6 Hz), 4.52 (d, 1H,
J = 6 Hz), 4.56–4.39 (m, 1H), 4.36 (d, 1H, J = 8 Hz), 4.33–4.27 (m,
1H), 4.11 (d, 1H, J = 8 Hz), 4.02 and 4.00 (two d, 1H, J = 7 Hz),
3.41 (dd, 2H, J = 8, 12 Hz), 3.33 and 3.32 (two s, 3H), 3.20 (dd, 1H,
J = 3, 15 Hz), 3.00 (dd, 1H, J = 3, 7 Hz), 2.93 (d, 1H, J = 15 Hz),
2.43 (dd, 1H, J = 4, 14 Hz), 2.31 (dd, 1H, J = 8, 14 Hz), 1.48 (s,
3H), 1.31 (s, 3 H).
13C NMR (CDCl3): = 139.8, 128.4, 128.2, 126.69, 126.66,
112.57, 112.56, 109.0, 108.9, 101.2, 86.84, 86.80, 84.7, 80.9, 74.5,
74.4, 73.1, 73.0, 72.9, 54.73, 54.70, 53.0, 52.8, 32.5, 32.3, 31.9,
31.8, 28.7, 26.5, 25.2.
Diastereomers 31b
1H NMR (CDCl3): = 7.42–7.30 (m, 5H), 4.991 and 4.985 (two s,
1H), 4.89 (dd, 1H, J = 3, 7 Hz), 4.80–4.76 (m, 1H), 4.52 (d, 1H,
J = 6 Hz), 4.50–4.45 (m, 1H), 4.36 (d, 1H, J = 7 Hz), 4.28–4.23 (m,
1H), 4.10–4.03 (m, 2H), 3.47 (d, 1H, J = 12 Hz), 3.40 (d, 1H,
J = 12 Hz), 3.334 and 3.325 (two s, 3H), 3.20 (dd, 1H, J = 4, 14
Hz), 2.90 (d, 1H, J = 14 Hz), 2.84 (dd, 1H, J = 3, 7 Hz), 2.50 (dd,
1H, J = 6, 14 Hz), 2.30 (dd, 1H, J = 6, 14 Hz), 1.47 (s, 3H), 1.31
and 1.30 (two s, 3H).
13C NMR (CDCl3): = 170.3, 170.0, 169.1, 169.0, 156.6, 134.9,
128.0, 116.53, 116.50, 98.9, 98.8, 74.13, 74.07, 72.7, 72.1, 71.1,
68.3, 62.0, 52.9, 28.3, 27.7, 25.4, 20.84, 20.78, 20.74, 20.72.
HRMS: m/z calcd for C25H33O11S2 [MH+] 573.1464. Found:
573.1441.
Monoadduct of 1 with 4-Formyldibenzo-24-crown-8;
Compound 15
13C NMR (CDCl3): = 139.8, 128.4, 128.2, 126.64, 126.59, 112.6,
109.00, 108.97, 101.28, 101.25, 86.84, 86.82, 84.8, 80.94, 80.93,
74.7, 74.6, 73.7, 73.6, 72.5, 72.4, 54.8, 54.7, 53.4, 53.2, 33.0, 32.9,
32.0, 31.8, 28.7, 26.6, 25.2.
HRMS: m/z calcd for C22H29O6S2 [MH – H2O]+: 453.1406. Found:
453.1406.
A solution of 1 (611 mg, 2.73 mmol) in THF (50 mL) was treated
with n-BuLi (1.6 M solution in hexanes, 3.27 mmol, 2.04 mL) and
reacted with 4-formyldibenzo-24-crown-814 (1 g, 2.1 mmol in 25
mL of THF) as described above for 21. The reaction mixture was
quenched with sat. NH4Cl and extracted twice with Et2O (2 10
Synthesis 2001, No. 8, 1133–1142 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Dithiane-Based Photolabile Molecular Systems
1141
mL). The combined organic extracts were dried (MgSO4), and the
solvent was then removed under vacuum. The residue was purified
by column chromatography (gradient elution with CHCl3–CH3OH,
100:0 to 95:5) to give 15 (1.1 g, 68%).
1H NMR (CDCl3): = 6.98–6.78 (m, 7H), 4.76 (dd, 1H, J1 = 3.0,
7.54 Hz), 4.21–4.09 (m, 8H), 4.00 (d, 1H, J = 7.8 Hz), 3.94–3.87
(m, 8H), 3.85–3.79 (m, 8H), 3.66–3.59 (s, 2H), 3.11–2.68 (m, 8H).
4.00 (m, 24H), 4.00–3.95 (m, 1H), 3.94–3.87 (m, 1H), 3.84–3.80
(m, 8H), 3.57–3.49 (m, 8H), 3.18–2.60 (m, 12H), 2.00–1.94 (m,
1H), 1.17–1.28 (m, 12H).
MS [MNa+]: m/z = 1374.9, 1375.9, 1376.9 (in agreement with iso-
tope pattern calculated for C73H92O16S4Na: m/z = 1374.5, 1375.5,
1376.5.)
Calixarene Adduct with 4-Formyl-dibenzo-24-crown-8;
Compound 36
Yield = 58%.
HRMS: m/z calcd for C32H43O8S4 [MH – H2O]+ 683.1841. Found:
683.1840.
Monoadduct of 1 with 3-Formylbenzo-18-crown-6;15
Compound 16
Yield = 94%.
1H NMR (CDCl3): = 6.82–7.02 (m, 3H), 5.00–5.08 (m, 1H), 4.31–
4.46 (m, 3H), 4.12–4.21 (m, 2H), 3.91–4.05 (m, 2H), 3.83–3.90 (m,
3H), 3.57–3.78 (m, 14H), 2.59–3.10 (m, 8H).
1H NMR (CDCl3): = 6.93–6.80 (m, 7H), 6.70–6.45 (m, 11H),
4.80–4.73 (m, 1H), 4.52–4.45 (m, 4H), 4.45–4.42 (m, 1H), 4.18–
4.04 (m, 16H), 4.02–3.94 (m, 1H), 3.93–3.88 (m, 9H), 3.86–3.80
(m, 16H), 3.57–3.49 (m, 8H), 3.18–2.60 (m, 12H), 1.98–1.92 (m,
1H), 1.28–1.17 (m, 12H).
MS [MNa+]: m/z = 1462.9, 1463.9, 1464.9 (in agreement with iso-
tope pattern calculated for C77H100O18S4Na: m/z = 1462.6, 1463.6,
1464.6).
Bis-adduct of 1 with 4-Formyldibenzo-24-crown-8; Compound
11
A solution of 1 (353 mg, 1.57 mmol) in THF (50 mL) was treated
with n-BuLi (1.6 M solution in hexanes, 3.78 mmol, 2.4 mL) and re-
acted with 4-formyldibenzo-24-crown-814 (1.6 g, 3.36 mmol in 25
mL of THF) as described above for 21. The reaction mixture was
quenched with sat. NH4Cl and extracted twice with Et2O (2 10
mL). The combined organic extracts were dried (MgSO4), and the
solvent was then removed under vacuum. The residue was purified
by column chromatography (gradient elution with CHCl3–CH3OH,
100:0 to 97:3) to give 11 (1.2 g, 61%).
Bis-Calixarene Adduct with 4,4’-Diformyldibenzo-18-crown-6;
Compound 33
Yield = 18%.
1H NMR (CDCl3): = 6.91–6.78 (m, 6H), 6.70–6.45 (m, 22H),
4.80–4.73 (m, 2H), 4.52–4.45 (m, 8H), 4.19–3.94 (m, 34H), 3.93–
3.85 (m, 2H), 3.84–3.79 (m, 16H), 3.56–3.49 (m, 16H), 3.19–2.60
(m, 24H), 2.02–1.95 (m, 2H), 1.28–1.17 (m, 24H).
MS [MNa+]: m/z = 2367.5, 2368.5, 2369.5, 2370.5 (in agreement
with isotope pattern calculated for C126H160O26S8Na: m/z = 2367.9,
2368.9, 2369.9, 2370.9).
1H NMR (CDCl3): = 7.04–6.78 (m, 14H), 4.86–4.74 (m, 2H),
4.24–4.06 (m, 16H), 4.04–3.96 (m, 2H), 3.96–3.70 (m, 32H), 3.15–
2.58 (m, 8H).
Bis-Calixarene Adduct with 4,4’-Diformyldibenzo-24-crown-8;
HRMS (characterized in a form of mono-sodium molecular ion): m/
z calcd for C57H76O18S4Na [MNa+]: 1199.3812. Found: 1199.3856.
Bis-adduct 34
Yield = 27%.
1H NMR (CDCl3): = 6.92–6.78 (m, 6H), 6.70–6.46 (m, 22H),
4.78–4.72 (m, 2H), 4.52–4.45 (m, 8H), 4.45–4.41 (m, 2H), 4.18–
4.02 (m, 24H), 4.00–3.95 (m, 2H), 3.93–3.87 (m, 10H), 3.86–3.79
(m, 24H), 3.57–3.48 (m, 16H), 3.19–2.60 (m, 24H), 2.01–1.96 (m,
2H), 1.25–1.17 (m, 24H).
MS [MNa+]: m/z = 2454.9, 2455.9, 2456.9, 2457.9, 2458.9 (in
agreement with isotope pattern calculated for C130H167O28S8Na: m/
z = 2454.9, 2455.9, 2456.9, 2457.9, 2458.9).
Bis-adduct of 1 with Benzo-18-crown-6; Compound 12
Yield = 46%.
1H NMR (CDCl3): = 6.81–7.01 (m, 6H), 5.00–5.09 (m, 2H), 4.25–
4.48 (m, 6H), 4.12–4.19 (m, 4H), 3.57–4.02 (m, 34H), 2.56–3.24
(m, 8H).
HRMS (characterized in a form of mono-sodium molecular ion): m/
z calcd for C41H60O14S4Na [MNa+]: 927.2764. Found: 927.2732.
Calixarene Adduct with 4-Formyl-dibenzo-18-crown-6:
Compound 35; Typical Procedure
Photofragmentation; Typical Procedure
A solution of the appropriate -hydroxyalkyl-1,3-dithiane, for ex-
ample, [9-(hydroxy-phenyl-methyl)-2,4,8,10-tetrathiaspiro[5,5]un-
A solution of 9 (387 mg, 0.4 mmol) in freshly distilled THF (20 mL)
was cooled to –78 °C under N2. n-BuLi (1.6 M solution in hexanes,
0.88 mmol, 0.55 mL) was added drop-wise with stirring. The result-
ing mixture was allowed to stand for 2 h at –20 °C. 4-Formyldiben-
zo-18-crown-6 (105 mg, 0.27 mmol) was added and reaction
mixture was stirred at r.t. overnight. The reaction mixture was
quenched with sat. NH4Cl, concentrated by evaporation, and ex-
tracted with CHCl3. The solvent was removed in vacuum and the
residue was purified by column chromatography, eluting first with
CHCl3–MeCN (1:1) to remove starting materials and then with
CHCl3–MeOH (98:2) to afford 35 (198 mg, 54%).
dec-3-yl]-phenyl-methanol (8,
8
mg, 0.02 mmol) and
benzophenone (7 mg, 0.04 mmol), in CD3CN (0.6 mL) was de-
gassed by four freeze-pump-thaw cycles and sealed in a Pyrex
NMR tube. Irradiations were carried out in a carousel Rayonet pho-
toreactor, with reaction progress monitored by NMR by disappear-
ance of the starting material and appearance of the aldehyde signal.
After 1 h of irradiation the conversion was about 80%.
Acknowledgement
1H NMR (CDCl3): = 6.93–6.80 (m, 7H), 6.70–6.45 (m, 11H),
4.80–4.74 (m, 1H), 4.52–4.46 (m, 4H), 4.45–4.41 (m, 1H), 4.20–
Support of this research by the National Science Foundation (Career
Award CHE-9876389) is gratefully acknowledged.
Synthesis 2001, No. 8, 1133–1142 ISSN 0039-7881 © Thieme Stuttgart · New York

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O. D. Mitkin et al.
PAPER
(7) We described the synthesis of compound 27 from estragol
earlier: Wan, Y.; Barnhurst, L. A.; Kutateladze, A. G. Org.
Lett. 2000, 2, 1133.
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References and Notes
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9924.
(2) For a review, see: Gröbel, B.-T.; Seebach, D. Synthesis
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(3) For the first short communication, see: Wan, Y.; Mitkin, O.;
Barnhurst, L.; Kurchan, A.; Kutateladze, A. Org. Lett. 2000,
2, 3817.
(4) The product is a mixture of diastereomers; while 1 itself is of
C2 symmetry, its disubstituted derivatives have allenic-type
chirality. Combined with (in general) two new stereogenic
centers at former carbonyls, it accounts for four pairs of
diastereomers. Due to the macromolecular nature of most of
the adducts described in this paper, we did not separate the
individual diastereomers (unless otherwise stated in the
experimental part). Reactions of bis-lithiated 1 with
symmetric ketones produced a single(racemic)product.
(5) Arduini, A.; Fanni, S.; Manfredi, G.; Pochini, A.; Ungaro,
R.; Sicuri, A. R.; Ugozzoli, F. J. Org. Chem. 1995, 60, 1448.
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(12) (a) Wang, H.; Sun, L.; Glazebnik, S.; Kang, Z. Tetrahedron
Lett. 1995, 36, 2953. (b) Hanessian, S.; Guindo, Y.
Carbohydr. Res. 1980, 86, C3. (c) Kometani, T.; Kondo, H.;
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(15) Jeong, K.-S.; Park, T.-Y. Bull. Korean Chem. Soc. 1999, 20,
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Synthesis 2001, No. 8, 1133–1142 ISSN 0039-7881 © Thieme Stuttgart · New York