LETTER
Photodecarboxylative Benzylation of N-Alkylphthalimides
2349
MeO
MeO
the phthalimide is typically achieved after 4–6 h with a final
pH of 9–10. Removal of the acetone from the reaction
mixture on a rotary evaporator yields the white, semi-
crystalline addition product, which is filtered off and dried.
When using the conditions of excimer irradiation (cf. ref.10),
20–30 g of crude product are obtained in 4–6 h of irradiation
in a flow setup with a 308 nm XeCl excimer system with 3.0
kW electrical power and an approximate photon flux of 3.5
Einstein/h. The crude material was thoroughly washed with
concd aq NaHCO3 and H2O and the solid material
recrystallized from EtOH to give an average yield of 91
5%.
COOH
O
OMe
MeO
O
H2O/acetone
K2CO3
MeO
MeO
N
Me
OH
N
Me
MeO
MeO
hν / N2
O
53%
5
1c
MeO
OMe
Scheme 4
3-(4-Methoxybenzyl)-3-hydroxy-2-methylisoindolin-1-
one(3b):
Colorless needles, mp 148 °C (from EtOH). 1H NMR (300
MHz, acetone-d6): d = 7.55 (d, J = 1.18 Hz, 1.18 Hz, 1 H),
7.54 (d, J = 1.24 Hz, 1 H), 7.43 (dd, 1 H, J = 2.70 Hz, 1.40
Hz, 1 H), 7.41–7.37 (m, 1 H), 6.82 (approx. dt, J = 8.76 Hz,
2 H), 6.62 (approx. dt, J = 8.78 Hz, 2 H), 3,44 (d, J = 13.96
Hz, 1 H), 3.24 (d, J = 13.96 Hz, 1 H), 3.03 (s, 1 H).
13C NMR (300 MHz, acetone-d6): d = 166.6, 158.9, 147.7,
132.7, 131.7, 131.4, 129.4, 127.7, 123.4, 122.6, 113.5, 90.9,
54.1, 41.8, 23.7. HRMS: m/z calcd for C17H15NO2 [M+ –
H2O]: 265.1103; found: 265.110. Anal. Calcd for
C17H17NO3: C, 72.07; H, 6.05; N, 4.94. Found: C, 71.98; H,
6.03; N, 4.92.
Adduct 5 was dehydrated as described above; further
transformations to the corresponding aristolactam are
currently investigated.
Acknowledgment
This work was generously supported by the Deutsche Forschungs-
gemeinschaft (DFG, Germany) and the Centre National de la
Recherche Scientifique (CNRS, France) in the context of a French-
German bilateral research project.
3-(3,4-Dimethoxybenzyl)-3-hydroxy-2-methylisoindolin-
1-one(3c):
References
Colorless needles, mp 145 °C (from EtOH). 1H NMR (300
MHz, acetone-d6): d = 7.64–7.62 (m, J = 7.42 Hz, 1.10 Hz,
1 H), 7.61–7.55 (m, 1 H), 7.47–7.39 (m, 1 H), 6.64 (d,
J = 8.19 Hz, 1 H), 6.49 (dd, J = 8.19 Hz, 2.03 Hz, 1 H), 6.33
(d, J = 2.03 Hz, 1 H), 3.66 (s, 1 H), 3.48 (s, 3 H), 3.43 (d,
J = 13.96 Hz, 1 H), 3.26 (d, J = 13.94 Hz, 1 H), 3.03 (s, 3 H).
13C NMR (300 MHz, acetone-d6): d = 167.7, 150.3, 150.0,
149.1, 133.0, 130.7, 124.7, 123.9, 115.4, 112.9, 92.3, 56.7,
56.7, 43.4, 24.9. HRMS: m/z calcd for C18H17NO3 [M+ –
H2O]: 295.1208; found: 295.121. Anal. Calcd for
C18H19NO4: C, 68.99; H, 6.11; N, 4.47. Found: C, 68.94; H,
6.12; N, 4.41.
(1) (a) Kumar, V.; Poonam Prasad, A. K.; Parmar, V. S. Nat.
Prod. Rep. 2003, 20, 565. (b) Chia, Y.-C.; Chang, F.-R.;
Teng, C.-M.; Wu, Y.-C. J. Nat. Prod. 2000, 63, 1160.
(c) Kim, S.-K.; Ryu, S. Y.; No, J.; Choi, S. U.; Kim, Y. S.
Arch. Pharm. Res. 2001, 24, 518.
(2) Arlt, V. M.; Stiborova, M.; Schmeiser, H. H. Mutagenesis
2002, 17, 265.
(3) Chen, Y.-C.; Chern, J.-J.; Chang, Y.-L.; Teng, C.-M.; Lin,
W.-Y.; Wu, C.-C.; Chen, I.-S. Planta Med. 2004, 70, 174.
(4) (a) Cepharanone A and B: Couture, A.; Deniau, E.;
Grandclaudon, P.; Lebrun, S. Synlett 1997, 1475.
(b) Eupolauramine: Hoarau, C.; Couture, A.; Cornet, E.;
Grandclaudon, P. J. Org. Chem. 2001, 66, 8064.
(c) Couture, A.; Deniau, E.; Grandclaudon, P. Tetrahedron
1997, 53, 10313.
(5) Botero Cid, H. M.; Tränkle, C.; Baumann, K.; Pick, R.;
Mies-Klomfass, E.; Kostenis, E.; Mohr, K.; Holzgrabe, U. J.
Med. Chem. 2000, 43, 2155.
(6) Griesbeck, A. G.; Kramer, W.; Oelgemöller, M. Synlett
1999, 1169.
(7) Griesbeck, A. G.; Oelgemöller, M. Synlett 1999, 492.
(8) Griesbeck, A. G.; Oelgemöller, M. Synlett 2000, 1455.
(9) Griesbeck, A. G.; Oelgemöller, M. Synlett 2000, 71.
(10) Oelgemöller, M.; Cygon, P.; Lex, J.; Griesbeck, A. G.
Heterocycles 2003, 59, 669.
(11) Detailed report: Warzecha, K.-D.; Görner, H.; Griesbeck, A.
G., manuscript in preparation.
(12) Griesbeck, A. G.; Görner, H. J. Photochem. Photobiol. A:
Chem. 1999, 129, 111.
(13) Griesbeck, A. G.; Henz, A.; Hirt, J.; Ptatschek, V.; Engel, T.;
Löffler, D.; Schneider, F. W. Tetrahedron 1994, 50, 701.
(14) Su, Z.; Mariano, P. S.; Falvey, D. E.; Yoon, U. C.; Oh, S. W.
J. Am. Chem. Soc. 1998, 120, 10676.
(15) Typical Procedure: A solution of 10 mMol of N-alkyl-
phthalimide 1, 12.5 mmol of arylacetic acid and 6 mmol of
K2CO3 in 400 mL of a acetone–H2O (3:1) mixture is
irradiated at l = 300 nm in a Rayonet photoreactor under a
gentle stream of nitrogen at r.t. The reaction progress is
monitored by TLC and pH-control; complete conversion of
(16) X-ray structure analyses of compounds 3b (CCDC 244764)
and E-4b (CCDC 244765) (from EtOH, colorless needles):
The data were obtained from a Nonius Kappa CCD-
diffractometer (MoKa irradiation) at 100 K. Structure was
solved with direct methods and refinement against F2
(SHELXL-97) with all independent reflexes.
(17) Typical Procedure: To a cooled solution (0 °C) of 3.5
mmol 3 in 100 mL CH2Cl2 5 drops of concd H2SO4 are
added. When TLC monitoring reveals the complete
disappearance of the starting material from the deep yellow
reaction mixture (not later than after 15 min) solid Na2CO3
is added. After filtration and evaporation of the solvent deep
yellow oil is obtained, from which the benzylidene
isoindolinones are isolated in a total yield of 85% by column
chromatography on silica using cyclohexane–EtOAc (7:3 →
1:1) as eluent.
(E)-3-(4-Methoxybenzylidene)-2-methylisoindolin-1-one
(E-4b):
Colorless needles, mp 144 °C (from benzene). 1H NMR (300
MHz, CDCl3): d = 7.83 (dm, J = 7.15 Hz, 1.28 Hz, 1 H),
7.43–7.28 (m, 5 H), 6.96 (dm, J = 8.72 Hz, 2 H), 6.46 (s, 1
H), 3.88 (s, 3 H), 3.37 (s, 3 H). 13C NMR (300 MHz, CDCl3):
d = 166.4, 159.2, 136.8, 134.8, 131.3, 130.7, 130.5, 128.9,
127.3, 123.0, 122.8, 114.0, 110.1, 55.3, 26.0. HRMS: m/z
calcd for C17H15NO2 [M+]: 265.1103; found: 265.110. Anal.
Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C,
76.94; H, 5.58; N, 5.25.
Synlett 2004, No. 13, 2347–2350 © Thieme Stuttgart · New York