Photodecarboxylative cyclizations of ω-phthalimido-ortho-phenoxy carboxylates

Article abstract of DOI:10.1016/j.tetlet.2005.03.090

ω-Phthalimido-ortho-phenoxy carboxylates efficiently undergo photodecarboxylative cyclizations in reasonable to good yields of 12-75%. Although the photocyclization efficiency decreases with increasing carbon chain lengths, target ring sizes up to 15 are

Full text of DOI:10.1016/j.tetlet.2005.03.090

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3395–3398
Photodecarboxylative cyclizations of x-phthalimido-ortho-phenoxy
carboxylates
Ae Rhan Kim,a Kyoung-Sub Lee,b Cheon-Woo Lee,b Dong Jin Yoo,b,*
Fadi Hatoumc and Michael Oelgemo¨llerc,*
aChonbuk National University, Department of Chemistry, 664-14 Doegjin-Dong, Chonju, Chonbuk 561-756, Republic of Korea
bSeonam University, Department of Chemistry, 720 Gwangchi-Dong, Namwon, Chonbuk 590-711, Republic of Korea
cDublin City University, School of Chemical Sciences, Dublin 9, Ireland
Received 23 December 2004; revised 8 March 2005; accepted 15 March 2005
Available online 2 April 2005
Abstract—x-Phthalimido-ortho-phenoxy carboxylates efficiently undergo photodecarboxylative cyclizations in reasonable to good
yields of 12–75%. Although the photocyclization efficiency decreases with increasing carbon chain lengths, target ring sizes up to 15
are successfully realized. Likewise, intermolecular photodecarboxylative additions of x-phenoxy carboxylates to N-methyl phthal-
imide give hydroxyphthalimidines in yields of 45–73%.
ꢀ 2005 Elsevier Ltd. All rights reserved.
The chemistry of electronically excited phthalimides is
dominated by electron and hydrogen transfer reactions.1
Among numerous synthetic applications, the photo-
chemical decarboxylation (PDC) of x-phthalimidoalkyl
carboxylates has been developed by Griesbeck and
co-workers as a versatile pathway to medium- and
large-ring heterocycles.2 We have recently reported the
successful synthesis of macrocyclic alkynes following
this PDC strategy.3 As an extension of our work, we
became interested in using ortho-substituted arenes as
rigid linkers between the phthalimide chromophore
and the terminal carboxylic acid chain. The U-shaped
geometry of the central skeleton should favor a close
contact geometry between the two active ends of the
molecule preferably for medium size ring systems. In
this paper, we describe the photochemistry of several
x-phthalimido-ortho-aryl carboxylates differing in the
terminal carbon chain length and compare it with
intermolecular addition reactions.
the simple decarboxylation (CO2H/H-exchange) prod-
uct 2 in a good yield of 62% (Scheme 1).4 The ortho-
CH3-group of 2 showed a characteristic 1H NMR singlet
at 2.21 ppm.
Although compound 2 is known to undergo photocycli-
zation to the corresponding five-membered ring via
hydrogen abstraction,5a,b we were unable to detect
any cyclization product under the given reaction condi-
tions in the NMR spectrum or via TLC analysis of the
crude reaction mixture.
For all other derivatives, we selected N-(2-hydroxyphen-
yl)-phthalimide as a useful and easily available building
block. In contrast to compound 1, the chain elongated
x-phthalimido-ortho-phenoxy acetate 3a readily gave
the six-membered product 4a in 75% isolated yield after
1
1 h of irradiation.6 In CDCl3, the H NMR spectrum
The first substrate we synthesized was 2-phthalimido-
phenyl acetic acid. Upon irradiation in aqueous acetone
for 1 h its corresponding potassium salt 1 readily gave
CO2K
O
O Me
N
hν
N
Keywords: Photodecarboxylation; Phthalimides; Cyclizations; Addi-
tion reactions; Photoinduced electron transfer.
acetone/H2O
O
O
*
Corresponding authors. Tel.: +82 63 620 0137; fax: +82 63 620 0075
(D.J.Y.); tel.: +353 1 700 5312; fax: +353 1 700 5503 (M.O.); e-mail
addresses: djyoo@seonam.ac.kr; michael.oelgemoeller@dcu.ie
1
2
Scheme 1. Simple decarboxylation of 1.
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.090

3396
A. R. Kim et al. / Tetrahedron Letters 46 (2005) 3395–3398
Table 2. Product yields and irradiation times for the photodecarb-
oxylative additions to 5
KO2C
( )
n
( )
N
O
O
n O
Entry
n
Time (h)
Yield 7 (%)
HO
hν
6a
6b
6c
6d
6e
6f
1
2
3
4
9
1
3
1
1
1
1
73
65
55
45
47
49
N
acetone/H2O
O
3a-f
O
4a-f
10
Scheme 2. Photodecarboxylative cyclization of 3.
No simple decarboxylation (COÀ2 /H-exchange) products
of 6a–f were formed under the given conditions. In
showed two clearly separated doublets for the O–CH2
group at 3.82 and 4.74 ppm with a large J coupling of
1
CDCl3, the N-methyl group showed H NMR singlets
2
at 2.86 (7a), 2.86 (7b), 2.77 (7c), 2.76 (7d), 2.91 (7e)
and 2.88 ppm (7f), respectively.
10.8 Hz. The hydroxy proton gave a broad singlet at
3.28 ppm, which was unambiguously assigned via H–D
exchange with D2O. Likewise, photolysis of compounds
3b–f furnished the corresponding cyclization products
4b–f (Scheme 2; Table 1). Noteworthy, the isolated
yields decreased from 42% to 12% with increasing chain
length. Furthermore, the irradiation time had to be
extended (especially for the long chain derivatives 3e, f)
in order to reach high conversion rates. In all cases,
the quaternary C–OH carbons showed characteristic
13C NMR resonances in CDCl3 at 82.3 (4a), 92.3 (4b),
93.3 (4c), 93.0 (4d), 93.2 (4e) and 92.4 ppm (4f),
respectively.
The key step of the mechanistic scenario (Scheme 4;
path A) is a rapid intramolecular electron transfer
(PET) via the excited 3p, p* triplet state (5: E00
=
3
3.1 eV) or the higher n, p* state (5: E00 ꢀ 3.6 eV) of
the phthalimide.9 Subsequent decarboxylation of the
carboxy radical gives the corresponding terminal
carbon radical. In the case of substrate 1, back elec-
tron transfer (BET) generates a carbanion,10 which is
protonated by water (path B). Although compound 2
is capable of undergoing a sequence of intramolecular
H-abstraction and photocyclization, this reaction is
highly sensitive to the irradiation conditions. Kanaoka
and co-workers reported that best results were
obtained with high-pressure mercury lamps, tert-butanol
as solvent and quartz vessels,5 and these conditions
clearly differ from ours.
To account for the decrease in isolated yields during the
intramolecular cyclization reaction, we have expanded
our study to intermolecular addition reactions.7 In all
cases examined, N-methylphthalimide 5 was used as a
model substrate and the phenoxy alkanoates 6 were var-
ied. Irradiation of 5 in aqueous acetone for 1–3 h in the
presence of 5 equiv of the potassium alkynoates 6a–f
gave the corresponding hydroxyphthalimidines 7a–f in
moderate to good yields between 45% and 73% (Scheme
3; Table 2).8 Judged by isolated yields and irradiation
times, the addition proceeded more efficiently than the
corresponding cyclization.
For all other derivatives, protonation and biradical
combination gave the desired cyclization products 4
(path C). The latter process also occurred for the
photodecarboxylative additions to the hydroxylphthal-
imidines 7. For x-phthalimidoalkoxy acetates, Yoon
et al. have recently postulated an alternative electron
transfer from the oxygen tether followed by a-decarbox-
ylation (path D; n = 1).11 This scenario would parallel
PET reactions of related a-trimethylsilyl (TMS) methyl
Table 1. Product yields and irradiation times for the photodecarb-
oxylative cyclizations of 1 and 3
Entry
n
Time
Yield 4 (%)
Ring-size
1
–
1
3
4
6
9
1 h
1 h
62 (2)
75
42
–
6
O
O
X
3a
3b
3c
3d
3e
3f
14 h
6 h
8
O
O
X
36
24
9
3Sens., PET
10 h
5 d
11
14
15
N
N
12
19
- CO2
10
5 d
A
O
1 (X = CH2)
3 (X = O(CH2)n)
D
1. BET
2. H+
1. H+
B
C
(X = O(CH2)n)
2. C-C
O
( )
N
O
nOPh
Me
HO
( )n
O
O
hν
O
N
O
O H3C
( )
N
n O
PhO
HO
( )n
N
Me +
OK
acetone/H2O
N
O
7a-f
O
5
6a-f
2
4
Scheme 3. Photodecarboxylative addition to 5.
Scheme 4. Mechanistic scenario.

A. R. Kim et al. / Tetrahedron Letters 46 (2005) 3395–3398
3397
ethers.12 In contrast, the results from our present inves-
tigation suggest that electron transfer occurs from the
carboxylate instead, independent from the position of
the oxygen tether. This interpretation is in line with ear-
lier studies on photoadditions of heteroatom-substituted
carboxylates,13 and is furthermore supported by the
oxidation potentials of the competing donors (Eox:
ROCH2TMS ꢁ RCOÀ2 6 PhOR < R2O).14,15
As for related anthranilic acid-based analogues,16 the
success of the cyclization depended on the chain length
and thus the ring-size of the corresponding product. In
compound 3a, the ortho-substitution pattern favors a
close contact for electron transfer and consequently,
the corresponding six-membered product was obtained
in the best yield of 75%. Noteworthy, a slightly lower
yield of 73% was reported for the corresponding ethyl-
ene-linked analogue.2b Further chain-elongation dis-
turbed the necessary approach for the biradical
combination due to steric overcrowding,17 and conse-
quently, the yields of 4 dropped below 20% and ex-
tended irradiation times were necessary to achieve high
conversion rates. On the contrary, the chain length ef-
fected the photodecarboxylative addition less and yields
were, in almost all cases, higher than for the intramolec-
ular counterparts after 1–3 h.
of H2O/acetone (1:1) was added and the mixture was
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 complete conversion (1 h to 5 d), most of the acetone
was evaporated and the remaining mixture was extracted
with CH2Cl2 (2 · 100 mL). The combined organic layers
were washed with 5% NaHCO3 and brine, dried over
MgSO4 and evaporated to dryness. The products were
obtained after column chromatography (eluent: n-hexane/
EtOAc = 3/1).
Selected physical and spectral data for the product N-(2-
methylphenyl)-phthalimide 2: colorless solid, mp 178–
180 ꢁC. 1H NMR (400 MHz, CDCl3): d = 2.21 (s, 3H),
7.20 (d, 1H, J = 8.0 Hz), 7.29–7.45 (m, 3H), 7.80 (dd, 2H,
J = 3.2, 5.6 Hz), 7.96 ppm (dd, 2H, J = 3.2, 5.6 Hz). 13C
NMR (100 MHz, CDCl3): d = 18.1, 123.7, 126.8, 128.6,
129.4, 130.5, 131.1, 131.9, 134.2, 136.4, 167.2 ppm. IR
(KBr): m = 3485, 3467, 3088, 3060, 2984, 2922, 1781, 1762,
1607, 1496, 1463, 1435, 1386, 1284, 1225, 1170, 1110, 1084,
1039, 942, 884, 856, 770, 720, 633, 527 cmÀ1
.
5. (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; (c) Kanaoka, Y.; Koyama, K.; Hatanaka, Y.
J. Photochem. 1985, 28, 575–576.
6. Selected physical and spectral data for the product 6a-
hydroxy-6,6a-dihydro-5-oxa-aza-benzo[a]fluoren-11-one
1
4a: colorless solid, mp 236–237 ꢁC. H NMR (400 MHz,
CDCl3): d = 3.28 (br s, 1H), 3.82 (d, 1H, J = 10.8 Hz),
4.74 (d, 1H, J = 10.8 Hz), 7.04–7.14 (m, 3H), 7.60 (m,
1H), 7.64–7.71 (m, 2H), 7.89 (d, 1H, J = 7.2 Hz),
8.19 ppm (d, 1H, J = 7.2 Hz). 13C NMR (100 MHz,
CDCl3): d = 70.6, 82.3, 116.9, 121.5, 122.3, 122.6, 123.0,
124.5, 125.4, 131.0, 131.6, 133.3, 141.8, 153.1, 164.7 ppm.
IR (KBr): m = 3286, 3063, 2993, 2860, 1676, 1612, 1500,
1466, 1381, 1306, 1277, 1221, 1132, 1082, 980, 881, 754,
Acknowledgements
This work was supported by grant R05-2002-000-01419-
0 from the Basic Research Program of the Korea
Science and Engineering Foundation (KOSEF). D.J.Y.
thanks KOSEF for a KOSEF-DFG fellowship during
the summer of 2004 (F03-2004-000-10046-0) and Profes-
sor Axel G. Griesbeck (University of Cologne) for his
support.
694, 656 cmÀ1
.
7. (a) Oelgemo¨ller, M.; Cygon, P.; Lex, J.; Griesbeck, A. G.
Heterocycles 2003, 59, 669–684; (b) Griesbeck, A. G.;
Oelgemo¨ller, M. Synlett 1999, 492–494.
8. General procedure for irradiation: N-Methylphthalimide
(2 mmol) was dissolved in acetone (150 mL). A solution of
the potassium phenoxy carboxylate (10 mmol) in water
(150 mL) was added, and the mixture was 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 slow stream of nitrogen. The progress of
the reaction was followed by TLC analysis or by passing
the departing gas stream through a saturated barium
hydroxide solution. After 1–3 h of irradiation, most of the
acetone was evaporated and the mixture was extracted
with CH2Cl2 (3 · 100 mL). The combined organic layers
were washed with 5% NaHCO3 and brine, dried over
MgSO4 and evaporated. The products were obtained after
column chromatography (eluent: n-hexane/EtOAc = 1/3).
Selected physical and spectral data for the product 3-
hydroxy-2-methyl-3-phenoxymethyl-2,3-dihydro-isoindol-
1-one 7a: colorless solid, mp 140–142 ꢁC. 1H NMR
(400 MHz, CDCl3): d = 2.86 (s, 3H), 4.15 (bs, 1H), 4.25
(d, 1H, J = 9.6 Hz), 4.36 (d, 1H, J = 9.6 Hz), 6.78 (d, 2H,
J = 8.0 Hz), 6.94 (t, 1H, J = 8.0 Hz), 7.22 (dd, 2H, J = 8.0,
8.0 Hz), 7.43 (t, 1H, J = 7.6 Hz), 7.49–7.69 ppm (m, 3H).
13C NMR (100 MHz, CDCl3): d = 24.0, 69.0, 88.5, 114.7,
121.5, 122.1, 123.1, 129.4, 129.8, 131.4, 132.1, 144.9, 157.8,
167.7 ppm. IR (KBr): m = 3307, 3073, 2977, 2885, 1940,
1696, 1599, 1493, 1432, 1395, 1306, 1292, 1251, 1177, 1159,
References and notes
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