Photoinduced electron transfer cyclizations of aryl-linked phthalimides

Article abstract of DOI:10.1016/j.tetlet.2011.07.069

The photochemistry of arene-linked phthalimides incorporating the carboxylate or thioether donor group was investigated. Simple N-phthalimidophenyl alkanoates exclusively gave photoreduction (CO ₂H/H-exchange) products. In contrast, ω-phthalimido-meta- phenoxy carboxylates underwent photodecarboxylative cyclizations in yields of 6-48%. Likewise, catechol-linked derivatives furnished analogue cyclization products in 18-38% yield. Using the photodecarboxylation protocol, macrocyclic target compounds with ring sizes up to 17 could thus be realized. Two model phthalimides containing a thioether branch at the ortho-position of the arene-linker gave the analogue seven-membered cyclization products in yields of 28% and 35%, respectively.

Full text of DOI:10.1016/j.tetlet.2011.07.069

Tetrahedron Letters 52 (2011) 5029–5031
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Photoinduced electron transfer cyclizations of aryl-linked phthalimides
Yong-Jun Lee a, Do-Hwan Ahn a, Kyoung-Sub Lee a, Ae Rhan Kim b, Dong Jin Yoo b,
,
⇑
Michael Oelgemöller c,
⇑
a Seonam University, Department of Chemistry, 720 Gwangchi-Dong, Namwon, Chonbuk 590-711, Republic of Korea
b Chonbuk National University, Department of Hydrogen and Fuel Cells Engineering, Specialized Graduate School, 567 Baekje-daero,
Deokjin-gu, Jeonju-si, Jeollabuk-do 561-756, Republic of Korea
c James Cook University, School of Pharmacy and Molecular Sciences, Townsville, QLD 4811, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
The photochemistry of arene-linked phthalimides incorporating the carboxylate or thioether donor group
Received 25 May 2011
Revised 1 July 2011
Accepted 15 July 2011
Available online 22 July 2011
was investigated. Simple N-phthalimidophenyl alkanoates exclusively gave photoreduction (CO2H/H-
exchange) products. In contrast,
x-phthalimido-meta-phenoxy carboxylates underwent photodecarboxy-
lative cyclizations in yields of 6–48%. Likewise, catechol-linked derivatives furnished analogue cyclization
products in 18–38% yield. Using the photodecarboxylation protocol, macrocyclic target compounds with
ring sizes up to 17 could thus be realized. Two model phthalimides containing a thioether branch at the
ortho-position of the arene-linker gave the analogue seven-membered cyclization products in yields of
28% and 35%, respectively.
Keywords:
Photodecarboxylation
Phthalimide
Photoinduced electron transfer
Photochemistry
Ó 2011 Elsevier Ltd. All rights reserved.
Photocyclization
The photochemistry of phthalimides has been intensively stud-
ied and numerous synthetically useful transformations with high
chemical and quantum yields have been developed.1 Among these,
intra- and intermolecular photodecarboxylations (PDC) have been
established as simple and efficient alternatives to thermal organo-
metallic reactions.2 Model reactions were furthermore realized on
macro- and micro-scales.3,4 We have recently described PDC cycli-
para-substituted analogue furnished 2c in only 8% yield after a
comparable time period. Consequently, prolonged irradiations
were applied for the extended carboxylates 1d and 1e and gave im-
proved yields of 28% (2d) and 15% (2e), respectively. The spectro-
scopic data of all products matched those reported in the
literature. As an example, the terminal CH3 group in 2e showed a
characteristic triplet at 0.95 ppm in the 1H NMR spectrum.8
zations of
x
-phthalimidoalkynoates to give macrocyclic alkynes
In our previous investigation we demonstrated that x-phtha-
with ring-sizes of up to 17.5 In the recent study, we expanded
the portfolio of this reaction and investigated the photochemistry
of related arene-linked phthalimides. Despite PDC-type reactions,
photoinduced electron transfer (PET) cyclizations of selected thio-
ether-containing compounds were additionally examined.6
limido-ortho-phenoxy carboxylates undergo efficient PDC cycliza-
tions with ring-sizes up to 15 atoms.9 The corresponding
x
-phthalimido-meta-phenoxy carboxylates 3a–d were conse-
quently investigated (Scheme 2, Table 2). To compensate for the
meta-substitution pattern in the ring closure step, longer carbon
linkers were specifically introduced. The pentylene (C5) moiety fur-
nished the 11-membered macrocycle 4a in a low yield of just 6%
together with larger amounts of unidentified decomposition prod-
ucts. Yields steadily increased with increasing chain-length and
following this extension strategy, the 16-membered product 4d
was subsequently obtained in 48% yield. While the 1H NMR spectra
were rather complex, all cyclization products 4a–d showed the
characteristic C–OH signal in their 13C NMR spectra at approxi-
mately 93 ppm.10 In all the cases examined, ‘simple’ decarboxyl-
ation products similar to 2 could be detected, but were not
isolated.
Simple N-phthalimidophenyl carboxylic acids were initially
chosen for this study. Irradiations of their corresponding potas-
sium carboxylates 1a–e in aqueous acetone furnished solely the
‘simple’ decarboxylation (CO2H/H-exchange) products 2a–e inde-
pendent of the substitution pattern (Scheme 1, Table 1).7 The
ortho- and meta-substituted carboxylates 1a and 1b gave the high-
est yields of 62% (2a) and 84% (2b), respectively, after short irradi-
ation times. As would be expected by the spatial separation of the
donor–acceptor couple (CO2ꢀ=Pht ¼ N) by the rigid arene ring, the
⇑
Corresponding authors. Tel.: +82 63 270 3608; fax: +82 63 270 3909 (D.J.Y.);
Catechol was additionally chosen as a central linker between two
flexible carbon chains. Four model compounds, 5a–d were prepared
and irradiated under PDC conditions (Scheme 3, Table 3). The ‘U-
tel.: +61 7 4781 4543; fax: +61 7 4781 6078 (M.O.).
E-mail addresses: djyoo@jbnu.ac.kr (D.J. Yoo), michael.oelgemoeller@jcu.edu.au
(M. Oelgemöller).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.069

5030
Y.-J. Lee et al. / Tetrahedron Letters 52 (2011) 5029–5031
Table 3
CO K
CH
3
2
Experimental details for PDC cyclizations of 5a-d
( )
( )
O
O
n
n-1
hν
acetone/H O
Entry
m
n
Yield of 6 (%)
Ring size
N
N
5a
5b
5c
5d
4
4
6
8
3
6
3
3
38
25
35
18
13
16
15
17
2
O
1a-e
O
2a-e
Scheme 1. Simple decarboxylation of 1a–e.
SCH3
S
O
HO
Table 1
hν
Experimental details for PDC of 1a–e
N
N
Entry
Substitution
n
Time (h)
Yield of 2 (%)
acetone
1a
1b
1c
1d
1e
Ortho
Meta
Para
Para
Para
1
1
1
2
3
1
2
2
26
24
62a
84
8
28
15
R
R
O
O
7a,b
8a,b
Scheme 4. PET cyclizations of 7a and 7b.
a
From Ref. 9
Table 4
Experimental details for PET cyclizations of 7a and 7b
n
Entry
R
Time (h)
Yield of 8 (%)
( )
KO C
2
n-3
( )
O
O
O
7a
7b
H
i-Pr
3
2
35
28
HO
hν, 24 h
N
N
acetone/H O
2
7a and 7b were irradiated in acetone for 2–3 h, cyclizations oc-
curred exclusively at the terminal SCH3-group and the seven-
membered products 8a and 8b were isolated in yields of 35% and
28%, respectively (Scheme 4, Table 4).13 In the 1H NMR spectrum,
the methylene protons in 8b showed two sets of doublets at
3.03/3.19 ppm and 3.53/3.89 ppm, respectively.14 For the iso-pro-
pyl-containing compound 7b, cyclization via competing C–H acti-
vation was not observed.15
O
3a-d
O
4a-d
Scheme 2. Photodecarboxylative cyclizations of 3a–d.
Table 2
Experimental details for PDC cyclizations of 3a–d
The key-step in both mechanistic scenarios (Scheme 5) is an
intramolecular electron transfer from the respective donor moiety
to the triplet excited phthalimide, the latter populated by sensiti-
zation with acetone.16,17 For all carboxylate containing derivatives
1, 3 and 5, electron transfer generates an unstable carboxy radical
(path A) which undergoes rapid decarboxylation to the analogous
carbon radical. Trapping experiments with electron-deficient al-
kenes proved the existence of such radicals.18 In the cases of 3
and 5, protonation and biradical combination yields the desired
cyclization products 4 and 6, respectively. When cyclization is
not possible as with compounds 1, back electron transfer (BET)
provides a carbanion,19 which is protonated by water to furnish
the decarboxylation products 2.20 This ‘simple’ decarboxylation
was a minor route for all other carboxylates as well. For substrates
7, an alternative PET from the thioether results in a radical-ion pair
(path B). Proton rearrangement from the terminal SCH3-group fol-
lowed by radical combination subsequently gives the cyclization
products 8.6,12
Entry
n
Yield of 4 (%)
Ring size
3a
3b
3c
3d
5
6
9
10
6
11
12
15
16
18
38
48
KO2C
( )
O
O
n
( ) n
O
HO
O
( ) m
hν, 4 h
acetone/H2O
O
N
N
( ) m
O
O
6a-d
5a-d
Scheme 3. Photodecarboxylative cyclizations of 5a–d.
In conclusion, the efficiency of PDC cyclizations depended crit-
ically on the substitution pattern of the arene and the extent of the
linking carbon chain(s). Short chains or remotely positioned car-
boxylates, as in compounds 1, solely gave decarboxylation. Ex-
tended carbon linkers can, however, compensate the
unfavourable meta-substitution as demonstrated for substrates 3.
The low yield and high degree of competing decomposition ob-
served during the formation of 4a suggests that the minimum
ring-size for successful cyclization may have been reached for this
compound. As for the catechol-linked derivatives 5, the ortho-sub-
stitution in combination with the flexible carbon linkers allows for
a close contact for electron transfer and cyclization. The notable
drop in yields for the larger rings may be caused by steric over-
crowding during the necessary biradical approach. Similar effects
shape’ of the catechol spacer eases the necessary approach for a suc-
cessful cyclization. As a result, the cyclization products 6a–d were
isolated in moderate yields of 18–38% after just 4 h of irradiation.
All compounds showed complex 1H NMR spectra but with distin-
guished signals for the aromatic isoindolinone group. In their 13C
NMR spectra, compounds 6a–d gave characteristic C–OH signals be-
tween 90 and 95 ppm.11 ‘Simple’ decarboxylation products were
again detected but could not be isolated in pure form.
Thioether-containing phthalimides can also be activated photo-
chemically for cyclizations.6,12 In contrast to the carboxylate sys-
tems
3 and 5 described above, the electron-donor moiety
remains in the product and is predominantly incorporated into
the macrocycle. When the two ortho-arene-linked phthalimides

Y.-J. Lee et al. / Tetrahedron Letters 52 (2011) 5029–5031
5031
10 min. The clear reaction mixture was subsequently irradiated (Rayonet
Photochemical Reactor RPR-208; k = 300 20 nm; ca. 800 W) at 15–20 °C in a
Pyrex tube while purging with a constant stream of dry nitrogen. The progress
of the reaction was followed by TLC analysis. After a set irradiation time (1–
26 h), most of the acetone was evaporated and the remaining mixture was
extracted with CH2Cl2 (3 ꢁ 30 mL). The combined organic layers were washed
with 5% NaHCO3 (30 mL) and brine (30 mL), dried over Na2SO4 and evaporated
to dryness. The products were obtained after column chromatography (SiO2, n-
hexane/EtOAc = 1:2).
Path A
CO
2
3
O
O
CH
2
-
Sens., PET (CO
)
2
N
N
- CO
2
O
1, 3, 5
O
8. Selected physical and spectral data for N-(4-methylphenyl)-phthalimide (2e):
colourless solid, mp 159–160 °C. 1H NMR (400 MHz, CDCl3): d = 0.95 (t, 3H,
J = 8.0 Hz), 1.64 (m, 2H), 2.62 (t, 2H, J = 8.0 Hz), 7.30 (m, 4H), 7.77 (dd, 2H,
J = 3.2, 5.6 Hz), 7.93 (dd, 2H, J = 3.2, 5.6 Hz) ppm. 13C NMR (100 MHz, CDCl3):
d = 28.9, 31.1, 80.6, 123.9, 126.0, 126.9, 131.7, 134.6, 139.4, 167.2, 176.8 ppm.
+
+
BET, H
H , C-C
O
CH
3
HO
IR (KBr):
m = 3475, 3050, 2939, 1771, 1713, 1611, 1518, 1462, 1421, 1386, 1289,
1219, 1175, 1119, 1096, 1081, 1019, 885, 810, 716, 531 cmꢀ1. MS (EI): m/
N
N
z = 265 [M+], 236, 204, 178, 152, 130, 104, 76.
9. Kim, A. R.; Lee, K.-S.; Lee, C.-W.; Yoo, D. J.; Hatoum, F.; Oelgemöller, M.
Tetrahedron Lett. 2005, 46, 3395–3398.
O
4, 6
O
2
10. Selected physical and spectral data for product 4d: colourless solid, mp 138–
139 °C. 1H NMR (400 MHz, CDCl3): d = 0.51 (m, 1H), 0.86–1.08 (br m, 11H),
1.38–1.46 (m, 2H), 1.65–1.74 (m, 2H), 1.99–2.03 (m, 2H), 3.34 (br s, 1H), 4.11–
4.17 (m, 1H), 4.19–4.52 (m, 1H), 6.85 (d, 1H, J = 6.4 Hz), 7.11 (s, 1H), 7.22–7.27
(m, 2H), 7.46 (dd, 1H, J = 7.2, 7.6 Hz), 7.52 (d, 1H, J = 7.6 Hz), 7.62 (dd, 1H,
J = 7.2, 7.6 Hz), 7.71 (d, 1H, J = 7.6 Hz) ppm. 13C NMR (100 MHz, CDCl3):
d = 21.5, 23.5, 25.5, 25.9, 26.3, 26.7, 27.0, 27.1, 35.5, 67.4, 93.4, 113.8, 114.6,
118.0, 121.6, 123.8, 129.6, 129.7, 131.0, 132.9, 136.5, 146.3, 158.3, 166.7 ppm.
Path B
SCH3
SCH3
O
O
N
O
3Sens., PET (S)
N
IR (KBr):
m = 3244, 3064, 2923, 2852, 1767, 1746, 1704, 1604, 1495, 1469, 1071,
1014, 894, 884, 791, 718, 700, 635, 593, 531 cmꢀ1
. MS (EI): m/z = 361
[M+ꢀH2O].
R
R
R
O
7
11. Selected physical and spectral data for product 6b: colourless solid, mp 183–
185 °C. 1H NMR (400 MHz, CDCl3): d = 1.33–1.53 (br m, 4H), 1.60–1.67 (m, 4H),
1.74–1.84 (br m, 2H), 1.87–1.94 (m, 2H), 2.09–2.21 (m, 2H), 3.25 (s, 1H), 3.29–
3.84 (br m, 2H), 3.91–3.95 (m, 2H), 4.04–4.17 (br m, 2H), 6.85–6.90 (m, 4H),
7.42 (dd, 1H, J = 7.2, 7.6 Hz), 7.50 (d, 1H, J = 7.2 Hz), 7.54 (dd, 1H, J = 7.2, 7.6 Hz),
7.64 (d, 1H, J = 7.6 Hz) ppm. 13C NMR (100 MHz, CDCl3): d = 22.9, 25.6, 26.5,
27.4, 28.1, 28.2, 35.5, 38.5, 67.8, 68.7, 91.4, 112.2, 113.5, 120.6, 120.9, 121.7,
~H+
SCH2
S
OH
N
HO
123.2, 129.4, 131.3, 132.1, 146.6, 148.6, 149.0, 167.7 ppm. IR (NaCl):
m = 3422,
C-C
2928, 1685, 1496, 1255, 1051, 824 cmꢀ1. MS (ESI, positive mode): m/z = 396.22
[M+H]+.
N
12. (a) Griesbeck, A. G.; Oelgemöller, M.; Lex, J. Z. Kristallogr.- New Cryst. Struct.
2002, 217, 235–236; (b) Griesbeck, A. G.; Oelgemöller, M.; Lex, J. J. Org. Chem.
2000, 65, 9028–9032; (c) Griesbeck, A. G.; Hirt, J.; Kramer, W.; Dallakian, P.
Tetrahedron 1998, 54, 3169–3180; (d) Sato, Y.; Nakai, H.; Wada, M.; Mizoguchi,
T.; Hatanaka, Y.; Kanaoka, Y. Chem. Pharm. Bull. 1992, 40, 3174–3180.
13. Typical irradiation procedure: A solution of the phthalimide 7 (1 mmol) in
100 mL of acetone was irradiated (Rayonet-Reactor RPR-208; k = 300 20 nm;
ca. 800 W) at 15–20 °C in a Pyrex tube while a gentle stream of dry nitrogen
was passed through it. The progress of the reaction was followed by TLC
analysis. After complete conversion was observed, the acetone was removed by
evaporation and the products were isolated by column chromatography (SiO2,
n-hexane/EtOAc = 1:2).
O
R
O
8
Scheme 5. Mechanistic scenarios.
were observed for anthranilic acid based amides and
dipeptides.21,22
x,x-
Acknowledgments
14. Selected physical and spectral data for product 8b: yellowish solid, mp 154–
155 °C. 1H NMR (400 MHz, CDCl3): d = 1.07 (d, 3H, J = 6.8 Hz), 1.21 (d, 3H,
J = 6.8 Hz), 2.72 (sept, 1H, J = 6.8 Hz), 3.03 (d, 1H, J = 14.3 Hz), 3.19 (d, 1H,
J = 14.3 Hz), 3.53 (d, 1H, J = 18.6 Hz), 3.75 (s, 1H), 3.89 (d, 1H, J = 18.6 Hz), 7.08
(dd, 1H, J = 1.9, 7.0 Hz), 7.29 (dd, 1H, J = 7.0, 7.9 Hz), 7.33 (dd, 1H, J = 1.9,
7.9 Hz), 7.55–7.59 (m, 2H), 7.66 (ddd, 1H, J = 1.0, 7.5, 7.6 Hz), 7.91 (d, 1H,
J = 8.2 Hz). 13C NMR (100 MHz, CDCl3): d = 23.1, 24.7, 29.1, 35.7, 44.8, 86.0,
121.9, 124.4, 126.1, 126.5, 129.1, 130.1, 131.3, 131.5, 133.1, 139.1, 146.4, 150.4,
This project was financially supported by the New & Renewable
Energy R & D program (2009 T100100606) and in parts by James
Cook University (JCU-CRIG 2011).
References and notes
167.0 ppm. IR (KBr):
m = 3331, 3271, 3057, 2952, 2910, 2804, 1689, 1615, 1495,
´
´
1. (a) Hovart, M.; Mlinaric-Majerski, K.; Basaric, N. Croat. Chem. Acta 2010, 83,
179–188; (b) McDermott, G.; Yoo, D. J.; Oelgemöller, M. Heterocycles 2005, 65,
2221–2257; (c) Oelgemöller, M.; Griesbeck, A. G. In CRC Handbook of Organic
Photochemistry and Photobiology; Horspool, W. M., Lenci, F., Eds., second ed.;
CRC Press: Boca Raton, 2004; pp 1–19. Chapter 84; (d) Oelgemöller, M.;
Griesbeck, A. G. J. Photochem. Photobiol. C: Photochem. Rev. 2002, 3, 109–127; (e)
Oelgemöller, M.; Kramer, W. H. J. Photochem. Photobiol. C: Photochem. Rev. 2010,
11, 210–244.
1467, 1411, 1359, 1237, 1147, 1110, 1089, 1054, 930, 886, 756, 697 cmꢀ1. MS
(EI): m/z = 307 [M+ꢀH2O], 290, 264, 242, 220, 191, 165, 137, 115, 89.
15. (a) Kanaoka, Y.; Nagasawa, C.; Nakai, H.; Sato, Y.; Ogiwara, H.; Mizoguchi, T.
Heterocycles 1975, 3, 553–556; (b) Kanaoka, Y.; Koyama, K. Tetrahedron 1972,
4517–4520.
16. (a) Hoffmann, N. J. Photochem. Photobiol. C: Photochem. Rev. 2008, 9, 43–60; (b)
Oelgemöller, M.; Bunte, J. O.; Mattay, J. In Synthetic Organic Photochemistry;
Griesbeck, A. G., Mattay, J., Eds.; Marcel Dekker: New York, 2004; pp 267–295.
Chapter 10.
17. (a) Görner, H.; Oelgemöller, M.; Griesbeck, A. G. J. Phys. Chem. A 2002, 106,
1458–1464; (b) Görner, H.; Griesbeck, A. G.; Heinrich, T.; Kramer, W.;
Oelgemöller, M. Chem. Eur. J. 2001, 7, 1530–1538.
18. Horvat, M.; Mlinaric-Majerski, K.; Griesbeck, A. G.; Basaric, N. Photochem.
Photobiol. Sci. 2011, 10, 610–617.
19. Yokoi, H.; Nakano, T.; Fujita, W.; Ishiguro, K.; Sawaki, Y. J. Am. Chem. Soc. 1998,
120, 12453–12458.
20. The mechanism mirrors that of related cyclization reactions, see: Griesbeck, A.
G.; Henz, A.; Kramer, W.; Lex, J.; Nerowski, F.; Oelgemöller, M.; Peters, K.;
Peters, E.-M. Helv. Chim. Acta 1997, 80, 912–933.
21. Griesbeck, A. G.; Kramer, W.; Heinrich, T.; Lex, J. Photochem. Photobiol. Sci. 2002,
1, 237–239.
22. (a) Griesbeck, A. G.; Heinrich, T.; Oelgemöller, M.; Molis, A.; Heidtmann, A.
Helv. Chim. Acta 2002, 85, 4561–4578; (b) Griesbeck, A. G.; Heinrich, T.;
Oelgemöller, M.; Lex, J.; Molis, A. J. Am. Chem. Soc. 2002, 124, 10972–10973.
2. (a) Griesbeck, A. G.; Kramer, W.; Oelgemöller, M. Synlett 1999, 1169–1178; (b)
Kramer, W.; Griesbeck, A. G.; Nerowski, F.; Oelgemöller, M. J. Inf. Rec. 1998, 24,
81–85.
3. (a) Griesbeck, A. G.; Maptue, N.; Bondock, S.; Oelgemöller, M. Photochem.
Photobiol. Sci. 2003, 2, 450–451; (b) Griesbeck, A. G.; Kramer, W.; Oelgemöller,
M. Green Chem. 1999, 1, 205–207.
4. Shvydkiv, O.; Gallagher, S.; Nolan, K.; Oelgemöller, M. Org. Lett. 2010, 12, 5170–
5173.
5. (a) Yoo, D. J.; Kim, E. Y.; Oelgemöller, M.; Shim, S. C. Photochem. Photobiol. Sci.
2004, 3, 311–316; (b) Yoo, D. J.; Kim, E. Y.; Oelgemöller, M.; Shim, S. C.
Heterocycles 2001, 54, 1049–1055.
´
´
6. (a) Hatanaka, Y.; Sato, Y.; Nakai, H.; Wada, M.; Mizuguchi, T.; Kanaoka, Y.
Liebigs Ann. Chem. 1992, 1113–1123; (b) Sato, Y.; Nakai, H.; Wada, M.;
Mizoguchi, T.; Hatanaka, Y.; Migata, Y.; Kanaoka, Y. Liebigs Ann. Chem. 1985,
1099–1118.
7. Typical irradiation procedure:
A mixture of K2CO3 (0.13 mmol) and the
phthalimide (0.26 mmol) in 100 mL of H2O/acetone (9:1) was sonicated for