Efficient approach to medium-sized cyclic molecules containing (E)-Alkene via z to e photochemical isomerization in the presence of AgNO3-impregnated silica gel

Article abstract of DOI:10.1246/cl.170937

Efficient synthesis of medium-sized cyclic molecules containing an (E)-alkene was performed via the highly (E)selective photochemical isomerization of the (Z)-isomer, facilitated by AgNO₃-impregnated silica gel.

Full text of DOI:10.1246/cl.170937

CL-170937
Received: October 5, 2017 | Accepted: November 13, 2017 | Web Released: January 11, 2018
Efficient Approach to Medium-sized Cyclic Molecules Containing (E)-Alkene via
Z to E Photochemical Isomerization in the Presence of AgNO3-impregnated Silica Gel
Kouhei Machida,1 Yuki Yoshida,1 Kazunobu Igawa,1,2 and Katsuhiko Tomooka*1,2
1Department of Molecular and Material Sciences, Kyushu University, 6-1 Kasuga-koen, Kasuga, Fukuoka 816-8580, Japan
2Institute for Materials Chemistry and Engineering, and IRCCS, Kyushu University,
6-1 Kasuga-koen, Kasuga, Fukuoka 816-8580, Japan
E-mail: ktomooka@cm.kyushu-u.ac.jp
Efficient synthesis of medium-sized cyclic molecules
containing an (E)-alkene was performed via the highly (E)-
selective photochemical isomerization of the (Z)-isomer, facili-
tated by AgNO3-impregnated silica gel.
Scheme 1]. This enhancement would be attributed to selective
adsorption of the (E)-isomer by the Ag-silica gel, where the (E)-
isomer was efficiently removed from the solution during the
photochemical isomerization process, as shown in Figure 1.10
To clarify the generality of the developed method, we
examined its application to other (E)-cyclic molecules. Herein,
we provide the details of our attempts.
At the outset, we examined the Z to E isomerization of
cyclooctene (3), a representative medium-sized alkene.2b The
reaction was performed in a three-necked round-bottomed Pyrex
flask equipped with a cylindrical Teflon-coated magnetic stir bar.
A side neck was capped with a rubber septum, the center neck
was fitted with a Teflon connecter holding a quartz photoinlet
adapter, and the other neck was fitted with a three-direction cock
connected to an argon balloon (Figure 2). The flask was charged
Keywords: Photochemical isomerization
|
Medium-sized cyclic molecules
AgNO3-impregnated silica gel
|
Medium-sized cyclic molecules containing an alkene group
often form the key skeleton of a variety of natural products.
Among them, (E)-alkene-containing derivatives have aroused
particular interest in structural organic chemistry because of their
unique stereochemical properties and reactivity.1 Therefore, a
variety of approaches for the synthesis of (E)-cycloalkenes and
their derivatives [(E)-cyclic molecules] have been attempted.2
However, the lower thermodynamic stability of the (E)-cyclic
molecules relative to that of the (Z)-isomer causes difficulty in
the (E)-selective synthesis by common approaches. For example,
one of the most efficient methods for constructing medium-
sized cyclic skeletons, ring-closing-olefin-methathesis (RCM),
generally affords the (Z)-cyclic molecules as the predominant
product.3,4 To address the issue of obtaining the (E)-cyclic
molecules, photochemical isomerization of (Z)-isomer to the
(E)-isomer is a prospectively efficient solution.5 Indeed, we
previously synthesized planar-chiral medium-sized cyclic mole-
cules with the (E)-alkene moiety, e.g., (E)-4-[7]orthocyclophene
[(E)-1a], where the acyclic diene 2 was subjected to RCM to
yield (Z)-1a, followed by Z to E photochemical isomerization by
irradiation with UV light (280 nm) in the presence of dimethyl
isophthalate (DMIP) or diethyl isophthalate (DEIP) as the
photosensitizer.5c,6,7 As expected, the reaction afforded (E)-1a in
22% yield, albeit the (E)-selectivity was not high [(E)-1a/(Z)-
1a = 22:78] [see a) in Scheme 1].
photochemical isomerization
UV light
( )-isomer
E
(
Z
)-isomer
weak
interaction
strong
interaction
Ag+
Ag+
Ag silica gel
Figure 1. Concept of photochemical isomerization in the
presence of Ag-silica gel.
light
source
More recently, we found that the addition of 10 wt % of
AgNO3-impregnated silica gel (10 wt % Ag-silica gel)8,9 dra-
matically improved the (E)-selectivity of the reaction to (E)-1a/
(Z)-1a = 89:11 [isolated yield of (E)-1a: 76%] [see b) in
quartz photoinlet adapter
optical fiber
Teflon connecter
rubber septum
UV (280 nm)
RCM
DMIP or DEIP
+
(Z)-1a
argon
balloon
substrate and
DEIP in pentane
UV light
2
(Z)-1a
(E)-1a
a) without Ag silica gel:
b) with 10 wt% Ag silica gel:
(E)-1a/(Z)-1a = 22:78 (quant)a
(E)-1a/(Z)-1a = 89:11 (88%)a
Ag silica gel
magnetic stir bar
a Combined yields of (E)-1a and (Z)-1a. Determined by GC analysis.
Figure 2. Reaction apparatus for photochemical isomerization
in the presence of Ag silica gel.
Scheme 1. Synthesis of (E)-1a from 2.
186 | Chem. Lett. 2018, 47, 186–188 | doi:10.1246/cl.170937
© 2018 The Chemical Society of Japan

UV (280 nm)
Table 1. Photochemical isomerization of (Z)-3
(Z)-1b
or
(Z)-1c
DMIP (2.0 equiv)
UV (280 nm)
Ag silica gel
X
+
X
pentane-Et2O
rt, 12 h
DEIP (2.0 equiv)
+
(Z)-3
pentane, rt
X = O: (Z)-1b
X = NTs: (Z)-1c
X = O: (E)-1b
X = NTs: (E)-1c
(Z)-3
(E)-3
(0.27 mmol)
(E)-1b/(Z)-1b = 31:69 (79%)a
(E)-1c/(Z)-1c = 26:74 (81%)a
a) without Ag silica gel:
Ag silica gel
AgNO3-content Amount
Time
/h
Yield
/%a
Entry
(E)-3/(Z)-3
b) with 10 wt% Ag silica gel: (E)-1b/(Z)-1b = 74:26 (88%)a
(E)-1c/(Z)-1c = 64:36 (67%)a
/wt %
/mg
a Combined yield of (E)-1 and (Z)-1. Determined by 1H NMR analysis.
1
2
3
4
5
6
®
5
10
20
10
10
none
400
400
400
500
500
42
42
42
42
42
24
23:77
75:25
93:7
77:23
97:3
87
81
81
73
88
72
Scheme 2. Photochemical isomerization of orthocyclophenes
(Z)-1b and (Z)-1c.
UV (280 nm)
67:33
10 wt% Ag silica gel
DEIP (2.0 equiv)
aCombined yields of (E)-3 and (Z)-3. Determined by GC
analysis.
+
(Z)-4
O
O
O
solvent, rt, 42 h
Si
Si
O
R
R
R
R
with Ag-silica gel and a solution of (Z)-3 and DEIP (2.0 equiv)
in pentane.11 UV light (280 nm) generated by an Asahi Spectra
MAX-301 was introduced into the flask through the optical fiber
inserted into the photoinlet adapter. The reaction mixture was
gently stirred at ambient temperature. After adequate photo-
irradiation, aminopropylated silica gel and Et2O were added to
the reaction mixture for the liberation of 3 from the Ag-silica
gel, and the resulting reaction mixture was washed with Et2O to
afford the crude product.
(Z)-4
(E)-4
(E)-4a/(Z)-4a = 89:11 (61%)a
(Z)-4a (R = tBu)
solvent: pentane
(Z)-4b (R = Ph)
solvent: pentane-Et2O
(E)-4b/(Z)-4b = >98:<2 (48%)a
a Combined isolated yield of (E)-4 and (Z)-4.
Scheme 3. (E)-Selective photochemical isomerization of dia-
lkoxysilane (Z)-4.
The reactions successfully provided (E)-3 as the predom-
inant product (Entries 2-6, in Table 1);12 this is in sharp contrast
with the reaction without the Ag-silica gel, which provided (Z)-3
predominantly [(E)-3/(Z)-3 = 23:77] (Entry 1). To optimize the
reaction conditions, we explored the influence of the AgNO3
content and the amount of Ag-silica gel. The reactions were
performed with 0.27 mmol of (Z)-3 in the presence of 400 or
500 mg of Ag-silica gel with UV irradiation for 42 h. The
reaction with 10 wt % Ag-silica gel (Entry 3) showed higher (E)-
selectivity than those with 5 or 20 wt % Ag-silica gel (Entries 2
and 4). The highest yield of (E)-3 was achieved with the use of
500 mg of 10 wt % Ag-silica gel (Entry 5). In this case, it was
confirmed that (E)-3 was efficiently adsorbed from the reaction
solution by the Ag-silica gel, based on GC analysis.13 On the
other hand, a shorter irradiation duration (24 h) provided low
(E)-selectivity of the product (Entry 6).
The developed protocol is applicable to the synthesis of
nine-membered heterocycles containing an (E)-alkene, such as
planar chiral (E)-[7]orthocyclophene 1b and 1c.14 As shown in
Scheme 2, the photochemical isomerization in the presence of
DMIP without the Ag-silica gel provided (E)-1b and (E)-1c as the
minor isomer [(E)-1b/(Z)-1b = 31:69, (E)-1c/(Z)-1c = 26:74].
In sharp contrast, the corresponding reactions with 10 wt % Ag-
silica gel provided (E)-1b and (E)-1c, predominantly [(E)-1b/
(Z)-1b = 74:26, (E)-1c/(Z)-1c = 64:36] in good yields.15
Furthermore, highly strained eight-membered dialkoxysi-
lane (E)-416 with very stable planar chirality was synthesized
with excellent (E)-selectivity using the developed protocol
(Scheme 3). The reaction of (Z)-4a (R = tBu) provided 4a in
61% yield with high (E)-selectivity [(E)-4a/(Z)-4a = 89:11].15
Moreover, the reaction of (Z)-4b (R = Ph) provided 4b with
almost perfect (E)-selectivity [(E)-4b/(Z)-4b in >98:<2] in 48%
isolated yield. The study of the significant substituent effect
of the R group on the (E)-selectivity of the photochemical
isomerization is in progress.
In summary, a concise method for the synthesis of medium-
sized cyclic molecules containing an (E)-alkene group was
developed. The key feature of the synthesis is the Z to E
photochemical isomerization in the presence of the Ag-silica gel.
The sequential approach with the RCM to provide medium-sized
(Z)-cyclic molecules and the Z to E photochemical isomerization
may be efficient for a variety of (E)-cyclic molecules. Further
synthetic applications of this approach are being explored.
This research was supported by JSPS KAKENHI Grants
JP16H04113 and JP16H01158 in Middle Molecular Strategy,
and the Cooperative Research Program “NJRC Mater. & Dev.”.
We thank T. Nishi (IMCE in Kyushu Univ.) for assistance with
the HRMS measurements.
Supporting Information is available at http://dx.doi.org/
10.1246/cl.170937.
References and Notes
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Chem. Lett. 2018, 47, 186–188 | doi:10.1246/cl.170937
© 2018 The Chemical Society of Japan | 187

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Preparation procedure for 10 wt % Ag-silica gel: To a
solution of AgNO3 (1.0 g) in distilled water (100 mL) in
an aluminum foil-wrapped one-neck round-bottom flask
(300 mL) was added silica gel (9.0 g). The mixture was
stirred for 20 min, and then water was evaporated under
reduced pressure with a rotary evaporator at 55 °C. The
residue in the flask was further dried under reduced pressure
with a rotary vacuum pump for 2 h at 90-110 °C by heating
with an oil bath.
9
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high repeatability of the reaction.
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photochemical isomerization of (Z)-3 was as high as (E)-3/
(Z)-3 = 38:62 in the presence of a photosensitizer such as
methyl 3,5-bis(trifluoromethyl)benzoate with UV irradiation
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the end of the reaction by GC analysis before treatment of
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adsorbed onto the Ag-silica gel from the reaction solution.
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purification via column chromatography using Ag-silica gel.
16 K. Tomooka, S. Miyasaka, S. Motomura, K. Igawa, Chem.®
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3
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DEIP is better than DMIP as a photosensitizer for the
reaction in pentane due to the higher solubility of DEIP in
this solvent.
6
7
8
Ag-silica gel is commonly utilized as a stationary phase for
188 | Chem. Lett. 2018, 47, 186–188 | doi:10.1246/cl.170937
© 2018 The Chemical Society of Japan