A strategy for the preparation of cyclic polyarenes based on single electron transfer-promoted photocyclization reactions

Article abstract of DOI:10.1007/s11164-011-0422-8

Single electron transfer (SET)-promoted photocyclization reactions of substrates comprised of benzylsilane tethered to phthalimides were subjected to an exploratory study in order to probe a new approach for the preparation of cyclic polyarenes. The resul

Full text of DOI:10.1007/s11164-011-0422-8

Res Chem Intermed (2012) 38:847–862
DOI 10.1007/s11164-011-0422-8
A strategy for the preparation of cyclic polyarenes
based on single electron transfer-promoted
photocyclization reactions
•
Hea Jung Park Jung Hei Choi Byeol Na Park
•
•
•
Ung Chan Yoon Dae Won Cho Patrick S. Mariano
•
Received: 24 September 2011 / Accepted: 8 October 2011 / Published online: 29 October 2011
Ó Springer Science+Business Media B.V. 2011
Abstract Single electron transfer (SET)-promoted photocyclization reactions of
substrates comprised of benzylsilane tethered to phthalimides were subjected to an
exploratory study in order to probe a new approach for the preparation of cyclic
polyarenes. The results show that UV irradiation of the substrates leads to efficient
photochemical reactions that are initiated by SET from benzylsilane moieties to the
excited phthalimide acceptor. Ensuing desilylation reactions of the benzylsilane
cation radical moieties in the intermediate zwitterionic biradicals and proton
transfer gives biradical precursors of the cyclic polyarene products. The observa-
tions made in this effort suggests that SET photochemical methods, which have
been employed earlier to generate cyclic poly-ethers, -thioethers and -amides, serve
as a useful method to access potentially interesting macrocyclic targets.
Keywords SET photochemistry ꢀ Cyclic polyarenes ꢀ Benzylsilanes ꢀ
Phthalimides
H. J. Park ꢀ J. H. Choi ꢀ B. N. Park ꢀ U. C. Yoon (&)
Department of Chemistry, and Chemistry Institute for Functional Materials, Pusan National
University, Busan 609-735, Korea
e-mail: ucyoon@pusan.ac.kr
D. W. Cho (&)
Department of Chemistry, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Korea
e-mail: dwcho00@yu.ac.kr
P. S. Mariano
Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque,
NM 87131, USA
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H. J. Park et al.
Introduction
Outside the areas of electrochemistry and electron impact mass spectrometry, little
was known prior to the early 1970s about the operation and implications of single
electron transfer (SET) in ground or excited state reactions of organic substances.
Several significant observations were made during the decade that had a major
impact on understanding the rates of SET and the role in governing the nature of
organic chemical reactions. The key earlier work by Marcus [1], which defined the
energetic requirements of SET, led to studies by Rehm and Weller [2], which
demonstrated the relationship that exists between the free energies and rate
constants for excited state SET. The Rehm–Weller formulation, arising from studies
of fluorescence quenching rates, served as the foundation for understanding what at
that time was a unique and rarely encountered phenomenon in organic photochem-
istry. More importantly, the effort gave photochemists the ability to predict when
SET processes would occur with rates that are competitive with those of other
excited state decay pathways. Particularly important in this regard are what have
become to be known as the Weller equations (Eq. 1), a set of relationships that
interrelate the redox (E1/2(?) and E1/2(-)) and excited state (E0,0) properties of
electron donors and acceptors to the free energies (DGoSET) and then the activation
free energies (DGàSET) and rate constants (kSET) for excited state SET (Eqs. 2 and 3).
Thus, by using these equations, one was now easily able to determine the free
energy change (DGoSET) for an intermolecular SET process occurring, for example,
between an electron donor having a known oxidation potential (E1/2(?)) and an
excited state acceptor with a known reduction potential (E1/2(-)) and excited state
energy (E0,0). Importantly, the Weller equations showed that when DGoSET is
negative for SET in an excited state donor–acceptor pair the rate constant for SET
(kSET) approaches the diffusion controlled limit (ca. 1 9 109 M-1 s-1), a value
which is in the regime of typical excited state decay processes, including
intersystem crossing, radiationless decay, light emission and chemical reactions.
Thus, in cases where DGoSET is negative, SET-promoted pathways that proceed
through ion radical intermediates would take place efficiently in photochemical
processes.
DGoSET ¼ E1=2ðþÞ ꢁ E1=2ðꢁÞ ꢁ E0;0 þ AECoulombic
ð1Þ
ð2Þ
ð3Þ
z
2
1=2
DGSET ¼ ðDGoSET=2Þ þ ððDGSoET=2Þ þ ðDG ð0ÞÞ Þ
z
z
kSET ¼ koexp ꢁ ðDGSET= RTÞ
Another equally important observation that contributed significantly to this area
was made by Arnold and his coworkers [3] in the early 1970s. It was only about a
decade earlier that organic chemists began to understand the mechanistic basis of
organic photochemical reactions that take place directly from excited state species.
Examples of this are found in the important investigations carried out by
Zimmerman and his coworkers [4], which led to formulations of organic chemical
(arrow pushing) mechanisms for interesting photochemical processes, like the cross-
conjugated cyclohexadienone and di-p-methane rearrangements.
123

Preparation of cyclic polyarenes
849
CO2Me
h
ν
Ph2CHCH2OMe
+
Ph2C CH2
MeOH
CO2Me
3
1
2
1. hν
2. SET
1
1. SET from
2. ~H+
CO2Me
MeOH
Ph2C
CH2
Ph2C
CH2OMe
+
CO2Me
4
1
Scheme 1
The key observation made by Arnold arose in a study of the methyl p-
acetylbenzoate (1) sensitized photoreaction of 1,1-diphenylethene (2, Scheme 1),
where the ether 3 is generated when methanol is used as solvent. This and other
observations led Arnold and his coworkers to propose that an SET pathway is
followed in this process, in which the excited state of 1 serves as the SET acceptor and
the alkene as the electron donor and, in addition, that a key step in product formation is
nucleophilic capture of the cation radical intermediate 4 by methanol [3].
The results of Arnold’s seminal studies suggested that a new family of excited
state reactions could be designed by taking into account the rates of SET and the
chemical properties of ion radicals. Thus, shortly after that time, several research
groups initiated efforts to discover new photochemical reactions that are driven by
excited state SET with the hope that these processes would add to the growing
repertoire of reactions that could be used to prepare organic substances. In the early
1980s, independently and nearly simultaneously groups headed by Mizuno [5, 6] and
Mariano [7, 8] recognized that SET-promoted photochemical reactions, in which
allyl and benzyl silanes participate as electron donors, might serve as both efficient
and useful preparative methods. Both groups reasoned that in these processes, SET
from the silicon-containing substrates 5 (Scheme 2) to excited state acceptors would
be facilitated by the presence of electropositive trialkylsilyl groups that stabilize the
forming cation radical intermediates 6. In addition, this thermodynamic stabilization
would be coupled to kinetic destabilization brought about by distribution of the
charged radical center into the C–Si bond. As a consequence, the allyl- and benzyl-
silane cation radicals would be subject to nucleophile-induced C–Si bond cleavage to
generate the corresponding allylic and benzylic radicals 7.
One of the first reported photochemical processes in which this pathway operates
is found in the reports by Mariano et al. [7, 8] describing the photoaddition reactions
of allylsilanes to 2-phenyl-1-pyrrolinium perchlorate (8) (Scheme 3). For example,
these workers found that irradiation of 8 in an acetonitrile solution containing
123

850
H. J. Park et al.
SET
Nu:
SiR3
SiR3
SiR3
5
6
7
Scheme 2
R'
Ph
R' R'
R
hν
+ R2HC
C
H
C
SiMe3
Ph
N
N
ClO4
MeCN
R
R'
Me
Me
9a
9b
9c
10a
10b
(R=R'=H)
(R=Me, R'=H)
(R=H, R'=Me)
(R=R'=H)
(R=Me, R'=H)
8
1. hν
2. SET
R'
R'
R'
R2C
C
H
C
SiMe3
Ph
R2C
C
H
C
Ph
N
N
R'
Me
Me
12
13a
13b
11
(R=R'=H)
(R=Me, R'=H)
11
Scheme 3
trimethylallylsilane (9a) results in formation of the 2-allylpyrrolidine adduct 10a.
The proposed mechanistic pathway for this process involves initial SET from 9a to
the singlet excited state of 8, giving the allylsilane cation radical 12 which then
undergoes acetonitrile-promoted desilylation to generate the radical pair 11 ? 13a.
Coupling of the radicals then provides adduct 10a. This mechanistic proposal was
consistent with the finding that photoaddition of the prenylsilanes 9b and 9c to
pyrrolinium salt 10b lead to generation of the same adduct 10b, demonstrating that
the same allyl radical intermediate 13b was involved in both processes.
At nearly the same time, the group headed by Mizuno [5, 6] observed that allylsilanes
participateinphotoadditionreactionswithelectron-deficientcyano-arenesand-alkenes.
One examplearisingfromtheir earlierworkis photoaddition oftrimethylallysilane9ato
1,4-dicyanobenzene (14), which produces adduct 15 via pathway where initial SET
generates the ion radical pair 16 ? 17 (Scheme 4). Desilylation of the allylsilane cation
radical followed by radical coupling and loss of HCN then forms 15.
Benzylsilanes were also observed to participate as electron donors in photoin-
duced SET reaction pathways [5, 9, 10]. As with those derived from allylsilanes,
benzylsilane cation radicals undergo nucleophile-promoted desilylation in processes
that generate benzyl radicals. Examples of photochemical reactions that are driven
by this chemical behavior are found in the photoadditions of trimethylbenzylsilane
(19) to 2-methyl- and 2-phenyl-2-pyrrolinium perchlorates 8 and 18 that produce
adducts 20 and 21 through routes that involve SET following excitation of either the
pyrrolinium salt (for 8) or benzylsilane (for 18) (Scheme 5) [9, 10].
Since the time of these early studies, many new SET-promoted photochemical
reactions have been discovered, some of which have been employed in the synthesis
123

Preparation of cyclic polyarenes
851
CN
CH2CH=CH2
hν
+
H2C CHCH2SiMe3
MeCN
CN
14
CN
15
9a
CN
H2C CH CH2SiMe3
CN
16
17
Scheme 4
R
SiMe3
hν
R
+
N
N
ClO4
MeCN
Me
Me
19
8
18
20
(R=Ph)
(R=Me)
(R=Ph)
21
(R=Me)
Scheme 5
of biologically important naturally occurring substances. Two examples of the
preparatively useful SET photochemical processes involving allyl- and benzyl-
silanes are the photocyclization reaction of the N-allysilane containing iminium salt
22, which serves as a cornerstone of a route for the synthesis of the harringtonine
alkaloid cephalotaxine (Scheme 6) [11], and the photoinduced conversion of the N-
benzyl-dihydroisoquinolinium salt 23, the key final step in a concise sequence for
the synthesis of the protoberberine alkaloid stylopine (Scheme 7) [12]. In addition,
the role played by desilylation of cation radicals of many other silicone-containing
electron donors, including a-silyl-ethers, -thioethers, -amine, -amides and -
sulfonamides, in preparatively useful SET-promoted photochemical reactions has
been demonstrated [13–16]. A specific example that can be used to point out the
preparative potential of SET photochemical processes of this type is the
photomacrocyclization reaction of the phthalimide 24, containing a polyether
tethered trimethylsilyl ether group (Scheme 8) [17]. In this system, excitation of the
phthalimide acceptor chromophore is followed by chain-assisted SET to form the
intermediate zwitterionic biradical 26, which following methanol-induced desily-
lation and proton transfer produces the biradical intermediate 27 that couple to
generate the macrocyclic polyether 25. Despite the complexity of this system and
the great distance that exists between the reactive centers, the macrocyclic polyether
(crown ether) containing product is generated in a quite acceptable 53% yield.
The results obtained from previous mechanistic and synthetic investigations of
the SET photochemistry of a-silyl substituted electron donors have recently
encouraged us to explore reactions of new types of donor–acceptor systems that
123

852
H. J. Park et al.
OMe
Bn
OMe
O
O
O
O
O
O
Bn
N
hν
-
ClO4
N
N
MeCN
SiMe3
HO
PvO
PvO
22
OMe
cephalotaxine
Scheme 6
O
O
O
-
ClO4
N
hν
MeCN
N
O
O
O
O
O
Me3Si
stylopine
23
Scheme 7
O
O
HO
5
hν
O
N
O
SiMe3
N
O
5
MeOH
O
O
24
25
1. h
ν
2.SET
O
OH
N
+
~SiMe3
O
O
N
O
SiMe3
O
5
5
O
O
27
26
Scheme 8
serve as useful synthetic methods for the preparation of novel macrocyclic
substances [18, 19]. Among a number of a-silyl electron donor candidates that can
be employed in SET-promoted photocyclization reactions, benzylsilanes would be
an interesting group owing to the fact that the processes would generate macrocyclic
polyarenes. As stated above, earlier studies demonstrated that, as a consequence of
their low oxidation potentials (E1/2(?) = ca. ? 1.6 V), benzylsilanes [20] would
participate (e.q., kSET ca. 1 9 1010 M-1 s-1) as electron donors with excited states
of electron acceptors like phthalimides (ES1/12(-) = ca. ? 2.3 V, ET1/12(-) = ca. ?
1.6 V) [21–23] that have appropriate reduction potentials. In addition, desilylation
of benzyl silane radical cations should take place rapidly to form benzyl radicals
that can undergo C–C bond forming reactions.
In order to probe the synthetic potential of the SET-promoted photochemical
reactions of systems comprised of benzylsilanes tethered to electron acceptors, we
123

Preparation of cyclic polyarenes
853
O
n
N
SiMe3
O
28 (n = 0)
29 (n = 1)
30 (n = 2)
Scheme 9
have prepared and investigated the phthalimide derivatives 28–30 shown in
Scheme 9. The results of this effort are described below.
Experimental
General procedures
1H- and 13C-NMR (200 MHz) spectra were recorded on CDCl3 solutions and
chemical shifts are reported in parts per million relative to CHCl3 peak (7.24 ppm
for 1H-NMR and 77.0 ppm for 13C-NMR) as an internal standard. Preparative
photochemical reactions were conducted with an apparatus consisting of a 450-W
Hanovia medium vapor pressure mercury lamp surrounded by a Pyrex glass filter in
a water-cooled quartz immersion well surrounded by the solution being irradiated.
The photolysis solutions were purged with nitrogen before and during irradiations.
The photolysates were concentrated under reduced pressure giving residues, which
were subjected to silica gel column chromatography. High resolution (HRMS) mass
spectra were obtained by use of electron impact ionization unless otherwise noted.
All starting materials used in the photoreactions derived from commercial sources.
All new compounds described were isolated as oils in [90% purity (by NMR
analysis) unless noted otherwise.
2-(20-Bromobenzyloxy)tetrahydropyran 34
To a CH2Cl2 (80 mL) solution containing 3,4-dihydropyran (3.0 g, 35.7 mmol) and
2-bromobenzyl alcohol 33 (6.0 g, 32.1 mmol) was added p-TsOH (0.12 g,
0.7 mmol) at 0 °C. The solution was warmed to and stirred at room temperature
for 2.5 h and then diluted with 5% K2CO3 and extracted with CH2Cl2. The organic
layers were dried and concentrated in vacuo to give a residue that was subjected to
1
column chromatography (CH2Cl2) to yield 34 (8.7 g, 100%) as a colorless oil: H
NMR (CDCl3) 1.52–1.94 (6H, m), 3.54–3.61 (1H, m), 3.89–3.97 (1H, m), 4.58 (1H,
d, J = 13.5 Hz), 4.74–4.80 (1H, m), 4.83 (1H, d, J = 13.2 Hz), 7.12–7.17 (1H, m),
7.32 (1H, t, J = 7.4 Hz) and 7.53 (2H, m); 13C NMR (CDCl3) 19.9, 26.0, 31.1, 62.7,
69.1, 98.9, 123.3, 127.9, 129.3, 129.6, 133.0, 138.3; HRMS (FAB) m/z 271.0305
(M??H, C12H16BrO2 requires 271.0334).
123

854
H. J. Park et al.
2-((Tetrahydropyranyl)oxymethyl)phenyl boronic acid 35
To a solution of anhydrous THF (80 mL) containing 34 (4.5 g, 16.6 mmol) was
added 2.5 M n-BuLi (8.0 mL, 20.0 mmol) at -78 °C. After stirring for 30 min at
-78 °C. B(OMe)3 (5.6 mL, 49.8 mmol) was added dropwise and the mixture was
warmed to and stirred at room temperature for 1 h. After addition of 80 mL of H2O,
the solution was extracted with diethyl ether. The ether layer was dried and
concentrated in vacuo to give a residue that was subjected to column chromatog-
raphy (EtOAc: hexane 1:2) to yield 35 (2.1 g, 53%) as a white crystalline solid: 1H
NMR (CDCl3) 1.86–1.56 (6H, m), 3.57–3.54 (1H, m), 3.91–3.88 (1H, m), 5.14 (3H,
s), 6.91 (1H, b), 7.40–7.35 (3H, m), 7.52–7.47 (1H, m) and 7.81–7.79 (1H, m); 13C
NMR (CDCl3) 20.32, 26.02, 31.27, 63.58, 71.86, 95.38, 121.71, 127.84, 131.26,
131.67 and 154.09.
2-(Trimethylsilylmethyl)benzyl bromide 36
To a solution of anhydrous ether (50 mL) containing PPh3 (11.3 g, 43.1 mmol) and
CBr4 (14.3 g, 43.1 mmol) was added the known [10] 2-(trimethylsilylmethyl)benzyl
alcohol (32) (7.0 g, 36.0 mmol) at 0 °C. The solution was stirred for 24 h at room
temperature followed by filtration. The filtrate was concentrated in vacuo giving a
residue that was subjected to column chromatography (hexane) to yield 36 (7.45 g,
1
80%) as a colorless oil: H NMR (CDCl3) 0.04 (9H, s), 2.28 (2H, s), 4.49 (2H, s)
and 7.01–7.33 (4H, m); 13C NMR (CDCl3) -0.8, 24.0, 33.6, 125.4, 129.4, 130.4,
131.2, 134.6, 140.5; HRMS (FAB) m/z 256.0285 (M?, C11H17BrSi requires
256.0283).
2-(o-(Silylmethyl)benzyl)benzyloxy tetrahydropyran 37
To a solution of toluene (15 mL) containing boronic acid 35 (0.9 g, 3.81 mmol) and
benzyl bromide 36 (1.0 g, 3.97 mmol) were added 1 M aq. Na2CO3 (4.8 mL) and
tetrakis(triphenylphosphine)palladium (0) (300 mg, 6.8 mol%). After 4 h stirring at
80 °C, the mixture was cooled to room temperature and filtered. The filtrate was
extracted with diethyl ether. The ether extract was dried and concentrated in vacuo
to give a residue that was subjected to column chromatography (diethyl ether:
hexane 1:15) to yield 37 (0.77 g, 57%) as a yellow oil: 1H NMR (CDCl3) 0.04 (9H,
s), 1.48–1.92 (6H, m), 2.12 (2H, s), 3.50–3.57 (1H, m), 3.86–3.3.94 (1H, m), 4.00
(2H, s), 4.52 and 4.82 (2H, two d, J = 12.3 Hz), 4.71 (1H, t, J = 3.4 Hz), 6.84–7.48
(8H, m); 13C NMR (CDCl3) d -1.0, 19.6, 23.7, 25.7, 30.8, 36.0, 62.3, 67.38, 98.1,
124.5, 126.3, 126.4, 128.2, 129.2, 129.3, 129.8, 130.0, 136.6, 136.8, 139.3, 139.4;
HRMS (FAB) m/z 369.2252 (M??H, C23H33O2Si requires 369.2250).
2-(20-(Trimethylsilylmethyl)benzyl)benzyl alcohol 38
To a solution of MeOH (10 mL) containing 37 (0.2 g, 0.54 mmol) was added
p-toluenesulfonic acid (10 mg, 0.06 mmol) at room temperature. After stirring for
2 h, the mixture was extracted with aq. NaHCO3 and diethyl ether. The organic
123

Preparation of cyclic polyarenes
855
layer was dried and concentrated in vacuo to give a residue that was subjected to
column chromatography (diethyl ether:hexane 1:15) to yield 38 (0.15 g, 100%) as a
colorless oil: 1H NMR (CDCl3) 0.06 (9H, s), 2.14 (2H, s), 4.01 (2H, s), 4.68 (2H, b)
and 6.80–7.46 (8H, m); 13C NMR (CDCl3) -0.6, 24.2, 36.5, 64.0, 125.0, 126.8,
127.3, 128.8, 128.8, 129.9, 130.1, 130.7, 137.2, 139.2, 139.5, 139.89; HRMS (EI)
m/z 284.1596 (M?, C18H24OSi requires 284.1596).
2-(20-(Trimethylsilylmethyl)benzyl)benzyl bromide 39
To a solution of anhydrous ether (40 mL) containing triphenylphosphine (1.67 g,
6.37 mmol) and CBr4 (2.11 g, 6.36 mmol) was added 38 (1.51 g, 5.31 mmol). The
solution was stirred for 2 h at room temperature and filtered. Concentration of the
filtrate in vacuo gave a residue that was subjected to column chromatography
1
(hexane) to yield 39 (1.52 g, 83%) as a yellowish oil: H NMR (CDCl3) 0.10 (9H,
s), 2.17 (2H, s), 4.11 (2H, s), 4.55 (2H, s) and 6.91–7.43 (8H, m); 13C NMR (CDCl3)
-0.6, 24.2, 32.8, 36.4, 125.1, 127.0, 127.5, 129.9, 129.9, 130.5, 130.7, 131.1, 136.5,
136.5, 140.1, 140.3; HRMS (FAB) m/z 346.0750 (M?, C18H23BrSi requires
346.0752).
2-(20-(20-(Trimethylsilylmethyl)benzyl)benzyl)benzyl alcohol 41
To a solution of toluene (20 mL) containing boronic acid 35 (0.92 g, 3.9 mmol) and
benzyl bromide 39 (1.42 g, 4.09 mmol) were added 1 M aq. Na2CO3 (4.8 mL) and
tetrakis(triphenylphosphine)-palladium(0) (310 mg, 6.9 mol%). The resulting solu-
tion was stirred for 4 h at 80 °C and filtered. The filtrate was extracted with diethyl
ether, giving an ether layer that was dried and concentrated in vacuo to give a
residue (1.5 g) containing coupled product 40. To the residue were added MeOH
(30 mL) and TsOH (100 mg, 0.6 mmol) and the resulting solution was stirred for
2 h at room temperature. The residue obtained by concentration of the solution in
vacuo was extracted with aq. NaHCO3 and diethyl ether. The ether extract was dried
and concentrated in vacuo to give a final residue that was subjected to column
chromatography (EtOAc : hexane 1:5) to yield 41 (1.14 g, 78%) as a yellowish oil:
1H NMR (CDCl3) -0.03 (9H, s), 2.04 (2H, s), 3.88 (2H, s), 4.04 (2H, s), 4.59 (2H,
s), 6.86–7.44 (12H, m); 13C NMR (CDCl3) -0.7, 24.2, 36.1, 37.3, 64.0, 125.0,
126.8, 127.2, 127.3, 127.4, 128.7, 128.9, 129.9, 130.1, 130.2, 130.4, 130.5, 136.9,
138.7, 139.2, 139.5, 139.9; HRMS (FAB) m/z 397.1965 (M??Na, C25H30OSiNa
requires 397.1964).
Benzylsilane linked phthalimides 28–30
To solutions of anhydrous THF (50 mL) containing the benzyl alcohol 32 (0.8 g,
4.12 mmol), 38 (1.4 g, 4.92 mmol), and 41 (1.0 g, 2.67 mmol) were added
phthalimide (0.73 g, 4.96 mmol for 32, 0.87 g, 5.91 mmol for 38, 0.47 g,
3.19 mmol for 41) and diisopropyl azodicarboxylate (DIAD) (1.0 g, 4.95 mmol
for 32, 1.19 g, 5.88 mmol for 38, 0.65 g, 3.21 mmol for 41). The resulting solutions
were stirred for 15 h at room temperature and concentrated in vacuo to give residues
123

856
H. J. Park et al.
that were subjected to column chromatography (diethyl ether:hexane 2:5 for 28,
EtOAc:hexane 1:2 for 29, EtOAc:hexane 1:5 for 30). The isolated substances were
purified by recrystallization (hexane) to yield 28 (0.65 g, 70%), 29 (1.13 g, 55%)
and 30 (0.58 g, 43%).
28: 1H NMR (CDCl3) 0.06 (9H, s), 2.39 (2H, s), 4.80 (2H, s), 6.98–7.23 (4H, m),
7.70–7.73 (2H, m), 7.82–7.87 (2H, m); 13C NMR (CDCl3) -1.5, 23.3, 39.4, 123.3,
124.4, 127.4, 128.5, 129.5, 132.1, 132.3, 134.0, 138.8, 168.3; HRMS (EI) m/z
323.1340 (M?, C19H21NO2Si requires 323.1342).
1
29: H NMR (CDCl3) 0.10 (9H, s), 2.22 (2H, s), 4.18 (2H, s), 4.87 (2H, s),
6.73–7.42 (8H, m), 7.66–7.69 (2H, m), 7.79–7.82 (2H, m); 13C NMR (CDCl3) -0.6,
24.0, 37.0, 39.7, 123.8, 124.9, 126.5, 127.3, 128.6, 129.4, 129.6, 130.9, 132.6,
134.4, 135.2, 137.0, 138.9, 139.7, 168.6; HRMS (EI) m/z 413.1812 (M?,
C26H27NO2Si requires 413.1811).
30: 1H NMR (CDCl3) 0.02 (9H, s), 2.12 (2H, s), 3.97 (2H, s), 4.20 (2H, s), 4.82
(2H, s), 6.74–7.48 (12H, m), 7.63–7.68 (2H, m), 7.71–7.76 (2H, m); 13C NMR
(CDCl3) -0.7, 24.2, 36.6, 37.1, 40.1, 123.8, 125.0, 126.7, 126.9, 127.4, 128.8,
129.3, 129.7, 129.8, 130.4, 130.6, 131.0, 132.6, 134.4, 135.3, 136.9, 138.6, 139.0,
139.5, 140.1, 168.5; HRMS (FAB) m/z 503.2279 (M?, C33H33NO2Si requires
503.2281).
Photoreaction of phthalimide 28
A nitrogen-purged solution of MeOH (200 mL) containing phthalimide 28 (250 mg,
0.77 mmol) was irradiated for 1 h by using Pyrex filtered light. The photolysate was
concentrated in vacuo to give a residue that was subjected to extraction with diethyl
ether. The organic extract was dried, concentrated in vacuo. The residue was
recrystallized by using EtOAc to give 42 (40 mg, 0.159 mmol, 23%) as a white
solid and the mother liquor was concentrated in vacuo to give a residue that was
subjected to column chromatography (CHCl3) to give 45 (110 mg, 72%), a known
1
substance whose H NMR spectroscopic properties closely match those previously
reported [24].
42: 1H NMR (CDCl3) 2.89 and 3.51 (2H, two d, J = 15.9 Hz), 4.07 (1H, s), 4.33
and 5.02 (2H, two d, J = 17.4 Hz), 7.17–7.69 (8H, m); 13C NMR (CDCl3) d 39.9,
40.1, 86.3, 122.3, 124.1, 127.1, 127.5, 127.7, 130.2, 130.3, 131.1, 131.2, 133.0,
148.6; HRMS (FAB) m/z 251.0928 (M?, C16H13NO2 requires 251.0946).
45: 1H NMR (CDCl3) 5.02 (2H, s), 6.38 (1H, s), 7.13–7.24 (4H, m), 7.47 (1H, t,
J = 7.2 Hz), 7.55 (1H, t, J = 7.2 Hz), 7.69 (1H, d, J = 7.8 Hz) and 7.85 (1H, d,
J = 7.2 Hz); 13C NMR (CDCl3) 43.5, 104.0, 120.8, 123.7, 127.3, 127.9, 128.5,
128.6, 129.8, 129.9, 130.8, 132.0, 134.5, 135.1, 166.7; HRMS (FAB) m/z 233.0839
(M?, C16H11NO requires 233.0841).
Photoreaction of phthalimide 29
A solution of 29 (250 mg, 0.60 mmol) in MeOH (200 mL) was irradiated by using
Pyrex filtered light for 1 h. The photolysate was concentrated in vacuo to give a
residue that was extracted with CH2Cl2. The organic layer was dried, concentrated
123

Preparation of cyclic polyarenes
857
in vacuo to give a white solid. The resulting solid was dissolved in MeOH and the
solution was filtered. The filtrate was concentrated in vacuo to give a white solid 43
(170 mg, 92%): 1H NMR (CDCl3) 3.54 (1H, s), 3.49 and 4.75 (2H, two d,
J = 14.1 Hz), 3.73 and 4.41 (2H, two d, J = 13.8 Hz), 4.06 and 4.14 (2H, two d,
J = 14.4 Hz), 6.35 (1H, d, J = 7.8 Hz), 6.56–6.61 (1H, m), 6.89–6.94 (1H, m),
7.12–7.22 (2H, m), 7.38–7.44 (4H, m), 7.60–7.72 (2H, m), 7.84 (1H, d, J = 7.2 Hz);
HRMS (FAB) m/z 342.1492 (M??H, C23H20NO2 requires 342.1494).
Photoreaction of phthalimide 30
A solution of 30 (250 mg, 0.50 mmol) in MeOH (200 mL) was irradiated for
40 min by using Pyrex filtered light. The photolysate was concentrated in vacuo to
give a residue that was extracted with CH2Cl2. The organic extract was dried and
concentrated in vacuo to give a residue. The residue was dissolved in a minimum
amount of CHCl3 and then diluted with an excess of hexane to form a white solid.
1
The solid was collected by filtration to yield 44 (90 mg, 42%): H NMR (CDCl3)
2.76 (1H, s), 2.96 and 3.58 (2H, two d, J = 15.3 Hz), 3.83 and 4.75 (2H, two d,
J = 15.6 Hz), 4.01 and 4.96 (2H, two d, J = 15.6 Hz), 4.58 and 4.63 (2H, two d,
J = 15.2 Hz), 6.64 (1H, d, J = 7.5 Hz), 6.96 (1H, t, J = 7.2 Hz) and 7.04–7.81
(14H, m); HRMS (FAB) m/z 432.1967 (M??H, C30H26NO2 requires 432.1964).
Dehydration reactions of 42–43 giving 45–46
To acetonitrile solutions (15 mL) containing the cyclic amidols 42 (100 mg,
0.4 mmol) and 43 (100 mg, 0.29 mmol) was added p-toluenesulfonic acid (30 mg,
0.18 mmol) and the resulting solutions were stirred for 24 h at room temperature.
The solutions were extracted with diethyl ether and aq. NaHCO3. The ether layers
were dried and concentrated in vacuo to give residues which were either subjected
to column chromatography (CHCl3) for the case in which 45 is formed (84 mg,
90%) or to recrystallization (CHCl3) for the cases of 46 (95 mg, 100%). Enamide 45
was found to have 1H NMR properties that closely match those previously reported
[24].
1
46: H NMR (CDCl3) 3.70 and 4.48 (2H, two d, J = 14.7 Hz), 4.58 and 4.71
(2H, two d, J = 14.7 Hz), 6.78 (1H, s), 7.19–7.38 (7H, m), 7.44–7.49 (2H, m),
7.57–7.62 (1H, m), 7.79–7.84 (2H, m); 13C NMR (CDCl3) d 39.1, 45.8, 105.2,
119.8, 123.6, 127.0, 127.4, 128.8, 128.9, 129.3, 129.6, 130.8, 131.2, 132.3, 132.4,
134.88, 136.0, 138.1, 138.3, 139.1, 140.6, 169.5; HRMS (FAB) m/z 323.1309 (M?,
C23H17NO requires 323.1310).
Results and discussion
Synthesis of trimethylsilylbenzyl tethered phthalimides 28–30
The synthetic pathways utilized to prepare the phthalimide derivatives 28–30 were
initiated by base-promoted introduction of the trimethylsilyl group at the benzylic
123

858
H. J. Park et al.
Phthalimide
PPh3, DIAD
OH
Me
1. n-BuLi
OH
28
SiMe3
2. Me3SiCl
31
32
Scheme 10
DHP
p -TsOH
OH
OTHP
OTHP
B(OH)2
1. n-BuLi
2. B(OMe)3
Br
Br
33
34
35
THPO
SiMe3
Pd(PPh3)4
CBr
SiMe3
Br
32
PPh3
35
37
36
HO
SiMe3
EtOH
p-TsOH
Phthalimide
PPh3, DIAD
29
38
Scheme 11
position of the o-methylbenzylalcohol 31 by utilizing the known procedure [12]
(Scheme 10). The resulting alcohol 32 along with phthalimide were then coupled by
using a Mitsunobu reaction, which resulted in formation of the mono-phenyl
tethered phthalimide 28. Preparation of the di- and tri-benzyl units needed to
produce 29 and 30, respectively, was initiated by formation of the THP protected
boronic acid 35 starting with o-bromobenzyl alcohol (33) (Scheme 11) via the
intermediate bromoarene 34. Palladium-induced coupling of 35 with the benzylic
bromide 36, formed from the corresponding benzyl alcohol 32, gave the
diarylmethane adduct 37 which was subjected to alcohol deprotection furnishing
38. Mitsunobu reaction between 38 and phthalimide gave rise to the bis-arene
tethered phthalimide 29. Finally, alcohol 38 was transformed into the corresponding
bromide 39, which underwent palladium coupling with boronic acid 35 to yield the
tribenzyl intermediate 40 (Scheme 12). Alcohol deprotection of 40 gave benzylic
alcohol 41, which underwent Mitsunobo coupling with phthalimde to generate the
tri-arene tethered phthalimide 30.
Photoreactions of phthalimides 28–30
Photoreactions of benzylsilane-tethered phthalimides 28–30 were carried out by
irradiation (Pyrex, k [ 290 nm) of MeOH solutions of the substrates. Photoreaction
of 28 carried out in this manner led to high yielding formation of the cyclic amidol
42 (23%) and enamide 45 (72%), the latter of which arises by dehydration of 42
(Scheme 13). Both of these substances have been described previously in
123

Preparation of cyclic polyarenes
859
OTHP
Br
SiMe3
SiMe3
Pd(PPh3)4
CBr
38
PPh3
35
39
40
OH
SiMe3
EtOH
Phthalimide
PPh3, DIAD
30
p-TsOH
41
Scheme 12
O
H
n
hν
MeOH
HO
+
N
SiMe3
N
N
n
n
O
O
O
45 (n = 0, 72%)
46 (n = 1, 0%)
47 (n = 2, 0%)
42 (n = 0, 23%)
43 (n = 1, 92%)
44 (n = 2, 42%)
28 (n = 0)
29 (n = 1)
30 (n = 2)
Scheme 13
Kanaoka’s report on the photochemistry of N-2-methylbenzyl-phtalimides (see
below) [24]. In contrast, the cyclic amidols 43–44 are formed as sole products in
photoreactions of the respective bis- and tris-arene containing phthalimides 29 and
30. The amidols 43 and 44 undergo quantitative conversion to enamides 46 and 47,
respectively, when treated with p-toluene sulfonic acid in MeCN.
1
Importantly, all spectroscopic data, including H- and 13C-NMR, and HRMS,
were in full accord with the structures assigned to the photoproducts. An unusual
1
feature of the H NMR spectroscopic data for enamide 46 led us to gain additional
information for its exact structural assignment. Specifically, the two sets of benzylic
protons both appear as two sets of doublet with germinal coupling constants (3.70
and 4.48 ppm; 2H, two d, J = 14.7 Hz, 4.58 and 4.71; 2H, two d, J = 14.7 Hz) in
this spectrum, suggesting that they are diastereotopically related. Although this
phenomenon could be a consequence of restricted rotation about the benzylic C–C
bonds in both the Z and E-stereoisomers of 46, it was expected that the rotation
would be more restricted in the latter isomer. However, that the stereochemistry of
46 is Z and not E was demonstrated by utilizing X-ray crystallographic analysis
(Fig. 1).
A common mechanism is at work in the photocyclization reactions of the
benzylsilane terminated phthalimide displayed in Scheme 14. In each case, sequen-
tial, methanol-promoted desilylation and proton transfer takes place on the
123

860
H. J. Park et al.
Fig. 1 Ortep plot of the X-ray crystallographic data of enamide 46
42-44
28-30
1. hν
2. SET
OH
N
O
n
n
+
~SiMe3
SiMe3
N
O
O
49
48
Scheme 14
intermediate zwitterionic biradicals 48 (Scheme 14) that are formed by either direct or
intervening arene ring assisted SET from the benzylsilane donor site to the
electronically excited phthalimide. This process gives rise to biradicals 49, which
undergo cyclization to generate the cyclic amidol products. It should be noted that the
oxidation potentials of dialkylbenzenes that mimic the central arene rings in 29 and 30
are sufficiently low (E1/2(?) ca. ?2.4 V) [25] to make them reasonably efficient
electron donors to the phthalimide singlet (ES1/12(-) = ca. ? 2.3 V) excited states. As
a result, the internal arene rings can also serve as electron donor sites that may facilitate
long-range SET and the formation of the reactive zwitterionic biradical intermediates.
It is interesting to compare the photocyclization reaction of the benzyltrimeth-
ylsilane containing substrate 28 to its analog 50 (Scheme 15) that lacks the
trimethylsilyl group. Indeed, analog 50 is known to participate in a related
sequential SET–proton transfer pathway that results in formation of the biradical
intermediate 49 (n = 0). Kanaoka and his coworkers observed that irradiation of 50
123

Preparation of cyclic polyarenes
861
O
Me
N
O
50
Scheme 15
in acetonitrile solutions promotes production of the cyclic amidol 42 as the
exclusive product but in only 18% yield. This yield contrasts dramatically with that
observed for the phtocyclization reaction of 28, which produces the same amidol 42
and derived enamide 45 in a combined yield of 95%.
Conclusion
Although preliminary, the results of the investigation described above show that the
SET photochemistry of benzylsilane terminated, arene-linked phthalimides serves
as a key step in routes for the preparation of cyclic polyarenes. Thus, similar to the
conclusions made in earlier studies of poly-donor-linked, silylmethyl ether
terminated phthalimide systems, in reactions of the arene linked substrates, SET
from the internal arene donor site(s) may facilitate long-range SET required to form
the reactive benzylsilane cation radical center. This mechanistic feature as well as
preparative applications of the process will be goals of our continuing investigations
in this area.
Acknowledgments This investigation was supported financially by the National Research Foundation
of Korea Grant to U.C.Y. supported by the Korean Government (KRF-2008-521-C00156). In addition, we
offer our congratulation to Professor Kazuhiko Mizuno on the excellent career he has had in the academic
profession and for the important scientific contributions he has made to the fields of organic chemistry
and organic photochemistry.
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