Job/Unit: O20822
/KAP1
Date: 18-09-12 16:53:08
Pages: 3
J. M. Aurrecoechea, R. Álvarez et al.
endo-dig-N-cyclizations, respectively.[3] Recently, the alternative 5-
ADDENDUM/CORRECTION
Table 3. Survey of reaction conditions for consecutive Sonogashira/
cyclization/intramolecular Heck coupling cascade of benzamide exo-dig-O-cyclization mode has also been observed, resulting in the
2a.[a]
regioselective formation of iminoisobenzofuran derivatives via Pd0-
catalyzed cyclization/coupling with aryl halides[4] or cyclizative di-
merization using CuII as both stoichiometric oxidant and cocata-
lyst.[5] In the present case, the initial heterocyclization of Sonoga-
shira adducts 5 derived from 2 and 3 is followed by an oxidative
intramolecular Heck-type coupling (Schemes 1 and 2, where Y =
–CONR) leading to 3,4-dihydro-1H-benzo[c]chromen-6(2H)-imine
derivatives (10). Incidentally, products 10 contain an isochromen-
1-imine core structure, the derivatives of which have attracted sig-
nificant recent synthetic attention[6] not only for being the nitrogen
analogues of the biologically important isocoumarins but also be-
cause of their own interesting properties.[6a,6d] Isochromen-1-imines
are also the products obtained when the Heck-type coupling is per-
formed intermolecularly.[7,8] In any event, in common with the pro-
cesses leading to iminoisobenzofurans mentioned above,[4,5] the Pd-
catalyzed formation of 10 from 2-alkynylbenzamides also follows
an initial O-cyclization pathway, albeit of the 6-endo-dig type,
therefore giving rise to a regiochemically different family of prod-
ucts. An even more fundamental difference arises in the nature of
the catalytic cycle, which is shared by products 9 and 10 and incor-
porates a coupling with a tethered alkene, thus providing a new
strategic element in the synthesis of various heterocyclic motifs.
Yield
[%]
Entry Conditions for step 2
1[b]
2
MA, air, 80 °C
47
60
22
37
37
70
(i) Evaporate Et3N; (ii) MA, DMF, air, 80 °C
(i) Evaporate Et3N; (ii) Et3N,[c] MA, DMF, air, 80 °C
(i) Evaporate Et3N; (ii) DMF, air, 80 °C
3
4[b]
5[b]
6
(i) Evaporate Et3N; (ii) ethyl acrylate,[d] DMF, air, 80 °C
(i) Evaporate Et3N; (ii) MA, DMF, catechol, air, 80 °C
[a] Relative amounts of reagents: PdCl2(PPh3)2 (5 mol-%), CuI
(1 mol-%), Et3N, 55 °C, MA (1 mol-equiv.), catechol (2 mol-%). [b]
Yield in the crude as determined by 1H NMR using (3,4-dimeth-
oxyphenyl)acetonitrile as internal standard. [c] 5 mol-equiv. of
Et3N were used. [d] 1 mol-equiv. of ethyl acrylate was used.
Supporting Information (see footnote on the first page of this arti-
cle): Reproduction of NMR spectra with the corrected structures
for compounds 10a–f.
Table 4. Preparation of 1-methylene-3,4-dihydro-1H-benzo[c]-
chromen-6(2H)-imines 10.
[1] C. Martínez, J. M. Aurrecoechea, Y. Madich, J. G. Denis, A. R.
de Lera, R. Álvarez, Eur. J. Org. Chem. 2012, 99–106.
[2] CCDC-884773 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[3] a) H. Sashida, A. Kawamukai, Synthesis 1999, 1145–1148; b)
N. G. Kundu, M. W. Khan, Tetrahedron 2000, 56, 4777–4792;
c) H. Cao, L. McNamee, H. Alper, Org. Lett. 2008, 10, 5281–
5284; d) M. Hellal, G. D. Cuny, Tetrahedron Lett. 2011, 52,
5508–5511; e) J. Y. Hou, D. Z. Wang, F. Li, Z. Y. Yan, Y. M.
Liang, Y. Q. Liu, Synth. Commun. 2012, 42, 1070–1084.
[4] Z. Y. Yan, C. M. Tan, X. Wang, F. Li, G. L. Gao, X. M. Chen,
W. S. Wu, J. J. Wang, Synlett 2011, 1863–1870.
Entry
2
R1
R2
10, Yield [%]
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
H
OMe
H
H
H
Ph
Ph
10a, 70
10b, 56
10c, 49
10d, 76
10e, 66
10f, 67
pMeOC6H4
pMeC6H4
pClC6H4
nBu
H
[5] B. Yao, C. Jaccoud, Q. Wang, J. Zhu, Chem. Eur. J. 2012, 18,
5864–5868.
[6] a) G. N. Liu, Y. Zhou, D. J. Ye, D. Y. Zhang, X. Ding, H. L.
Jiang, H. Liu, Adv. Synth. Catal. 2009, 351, 2605–2610; b) G.
Bianchi, M. Chiarini, F. Marinelli, L. Rossi, A. Arcadi, Adv.
Synth. Catal. 2010, 352, 136–142; c) M. Bian, W. Yao, H. Ding,
C. Ma, J. Org. Chem. 2010, 75, 269–272; d) T. Mitra, S. Dutta,
A. Basak, Tetrahedron Lett. 2010, 51, 2828–2831.
[7] R. Álvarez, C. Martínez, Y. Madich, J. G. Denis, J. M. Aurrec-
oechea, Á. R. de Lera, Chem. Eur. J. 2010, 16, 12746–12753.
[8] R. Álvarez, C. Martínez, Y. Madich, J. G. Denis, J. M. Aurrec-
oechea, Á. R. de Lera, Chem. Eur. J. 2012, DOI: 10.1002/
chem.201201973.
1H-benzo[c]chromen-1-ylidene}acetate (10c), ethyl (E)-2-[(Z)-6-(p-
tolylimino)-2,3,4,6-tetrahydro-1H-benzo[c]chromen-1-ylidene]acet-
ate (10d), ethyl (E)-2-{(Z)-6-[(4-chlorophenyl)imino]-2,3,4,6-tetra-
hydro-1H-benzo[c]chromen-1-ylidene}acetate (10e), ethyl (E)-2-
[(Z)-6-(butylimino)-2,3,4,6-tetrahydro-1H-benzo[c]chromen-1-ylid-
ene]acetate (10f).
Additional Discussion
Palladium-catalyzed cycloisomerization reactions of 2-alkynylbenz-
amides have been shown in various instances to proceed with for-
mation of isoindolone or isoquinolone products via 5-exo- or 6-
Received: June 20, 2012
Published Online:
2
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Eur. J. Org. Chem. 0000, 0–0
Martinez, Claudio
