Palladium-catalyzed regioselective 5-exo-o-cyclization/oxidative Heck cascades from o-alkynylbenzamides and electron-deficient alkenes

Article abstract of DOI:10.1002/ejoc.201402709

A Pd-catalyzed 5-exo-selective oxycyclization/oxidative Heck coupling cascade is described, starting from readily available ortho-alkynylbenzamides and functionalized olefins. The key to a high regioselectivity in the cyclization step is the choice of catalyst and/or additives. Thus, Pd(OAc)₂ provides the desired 5-exo products predominantly, whereas with PdCl₂ or Pd(TFA)₂, the corresponding 6-endo products prevail. The subsequent oxidative Heck-type coupling takes place stereoselectively with the very predominant formation of E isomers, leading to an effective preparation of structurally diverse carbonyl-substituted allylideneisobenzofuranimines.

Full text of DOI:10.1002/ejoc.201402709

FULL PAPER
DOI: 10.1002/ejoc.201402709
Palladium-Catalyzed Regioselective 5-exo-O-Cyclization/Oxidative Heck
Cascades from o-Alkynylbenzamides and Electron-Deficient Alkenes
Youssef Madich,[a,b] Rosana Álvarez,*[c] and José M. Aurrecoechea*[a]
Dedicated to the memory of Professor Alan R. Katritzky
Keywords: Homogeneous catalysis / Palladium / Cyclization / Cross-coupling / Regioselectivity / Oxygen heterocycles
A
Pd-catalyzed 5-exo-selective oxycyclization/oxidative
with PdCl2 or Pd(TFA)2, the corresponding 6-endo products
Heck coupling cascade is described, starting from readily
prevail. The subsequent oxidative Heck-type coupling takes
available ortho-alkynylbenzamides and functionalized ole- place stereoselectively with the very predominant formation
fins. The key to a high regioselectivity in the cyclization step of E isomers, leading to an effective preparation of structur-
is the choice of catalyst and/or additives. Thus, Pd(OAc)2 pro- ally diverse carbonyl-substituted allylideneisobenzofuranim-
vides the desired 5-exo products predominantly, whereas
ines.
have been shown to be very regioselective. For example,
products derived from the 5-exo-heterocyclization mode
were obtained with aryl halide coupling agents.[4] Similarly,
oxidative dimerization[5] and oxidative coupling to an o-alk-
ynylaniline[6] or carbon monoxide[7] are also 5-exo-selective
reactions. On the other hand, the corresponding oxidative
coupling reactions of o-alkynylbenzamides with electron-
deficient alkenes have provided products 5 derived from 6-
endo-cyclizations.[8–10] Significantly, no example of a re-
Introduction
Metal-catalyzed intramolecular additions of heteroatom-
based nucleophiles onto C–C triple bonds have found wide-
spread application in the synthesis of a variety of heterocy-
clic derivatives that often have useful properties, or at least
are related to products with known practical applications.[1]
The merits of this type of strategy in the construction of
complex molecules are even more evident when the metal-
promoted cyclization is followed by an additional coupling
to an external reagent.[2] Further interest stems from the
possibility of gaining access to different families of prod-
ucts, using the same starting materials, by exercising ef-
ficient control over the regiochemistry (exo/endo) of the cy-
clization.[3] Thus, for substrates of the o-alkynylbenzamide
type (1 in Scheme 1), the formation of isofuranimine- and
isochromenimine-derived products has been reported, pre-
sumably arising from the corresponding intermediate palla-
dium complexes 2 and 3 as a result of 5-exo- and 6-endo-O-
cyclizations, respectively. In fact, such palladium-catalyzed
heterocyclization/coupling cascade reactions of substrates 1
[a] Departamento de Química Orgánica II, Facultad de Ciencia y
Tecnología, Universidad del País Vasco UPV/EHU,
Apartado 644, 48080 Bilbao, Spain
E-mail: jm.aurrecoechea@ehu.es
[b] Laboratoire de Chimie Bio-Organique et Macromoléculaire,
Faculté des Sciences et Techniques Marrakech, Université Cadi
Ayyad,
BP 549, Marrakech, Morocco
[c] Departamento de Química Orgánica, Facultad de Química,
Universidade de Vigo,
Campus As Lagoas-Marcosende, 36310 Vigo, Spain
E-mail: rar@uvigo.es
Homepage: http://webs.uvigo.es/delera/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402709.
Scheme 1. Palladium-catalyzed oxycyclization/coupling reactions
of o-alkynylbenzamides.
Eur. J. Org. Chem. 2014, 6263–6271
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6263

Y. Madich, R. Álvarez, J. M. Aurrecoechea
FULL PAPER
gioselectivity switch between the two modes (exo/endo) of der an air atmosphere. As shown in Table 1, entry 1, iso-
cyclization has been described in the literature for a particu-
lar type of coupling agent starting from o-alkynylbenz-
amides.
chromenimine 5a was obtained exclusively under those con-
ditions.[8] In related work where the Heck-type coupling was
intramolecular, the formation of regioisomeric side-prod-
ucts was noticed when the coupling reactions were carried
out in the presence of Et3N.[9] Therefore, the conditions of
Table 1, entry 1 were modified by adding one equivalent of
Et3N. This resulted in the formation of a small amount of
a 5-exo-cyclization-derived product 4a, accompanying the
major product 5a (Table 1, entry 2). Increasing the amount
of Et3N fivefold had only a modest effect on the amount of
4a produced (Table 1, entry 3), whereas the alternative use
of the stronger amine base DBN (1,5-diazabicyclo[4.3.0]-
non-5-ene) resulted in cycloisomerization of the starting 1a
and formation of an isoindolone-type product 7a (Table 1,
entry 4, Figure 1). A control experiment revealed that this
N-cyclization was not catalyzed by PdII, and that cyclo-
isomerization was probably promoted by a Brönsted base/
Brönsted acid couple.[12] On the other hand, the addition of
a small amount (10%) of other additives (KOBz, NaOAc,
K2CO3) produced a more pronounced increase in the rela-
tive amounts of 5-exo-cyclization-derived products (Table 1,
entries 5–7). The best overall exo/endo ratio was obtained
with K2CO3 (Table 1, entry 7), but this reaction was compli-
cated by competing cycloisomerization, and also gave a rel-
atively low Z/E ratio at the exocyclic C=C bond. In those
three reactions, the formation of oxidative dimerization
In this paper, we describe a palladium-catalyzed 5-exo-
dig-selective O-cyclization/oxidative-Heck cascade from o-
alkynylbenzamides and electron-deficient alkenes, leading
to the formation of products 4, whose isobenzofuranimine
core structure has been the subject of significant synthetic
attention in recent years.[4–7,11] These results complement
previous related work where, under modified conditions,
the regiochemistry of cyclization was 6-endo.[8–10] Remarka-
bly, the regioselectivity change from endo to exo is triggered
by the presence of carboxylate or carbonate anions in the
reaction medium. Finally, in selected cases, hydrolysis of the
imino functionality of products 4 has been undertaken to
demonstrate the potential of the method to also provide a
route to the corresponding lactone derivatives.
Results and Discussion
A survey of reaction conditions was conducted with a
representative substrate 1a (Table 1). Standard conditions
for
regioselective
6-endo-O-cyclization/intermolecular
Heck-coupling cascades involve treatment of a substrate 1
with a catalytic amount of PdCl2(PPh3)2 (5 mol-%), KI
(0.5 equiv.), and excess ethyl acrylate in DMF at 80 °C un-
Table 1. Representative experiments in the optimization of the reaction conditions.[a]
[Pd]
additive (n1)
n2
T
4a,4aЈ[b]
5a
6a
1
2
3
4
5
6
7
8
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd(OAc)2/PPh3
Pd(TFA)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
–
6
6
6
6
6
6
6
6
80
80
80
80
80
80
80
80
80
80
35
–
82[c]
86[c]
82
–
53
34
15[e]
8
–
Et3N (1)
Et3N (5)
DBN (5)
KOBz (0.1)
NaOAc (0.1)
K2CO3 (0.1)
–
8 (80:20)
2
[d]
12 (82:18)
[e]
–
5
40 (77:23)
49 (87:13)
67 (78:22)[e]
52 (89:11)
1.5 (Z)
67 (91:9)
75 (97:3)
13
10[e]
34
–
22
18
9
10
11
–
6
10
20
91
9
6
DMAP (0.05)
DMAP (0.01)
[a] Reaction conditions: A solution of 1a, palladium complex [Pd] (5 mol-% relative to 1a), PPh3 (where appropriate, 10 mol-%), KI
(0.5 equiv.), an additive (where appropriate, n1 = number of equivalents), and ethyl acrylate (n2 = number of equivalents) in DMF (8.5 mL/
mmol) was heated at the indicated temperature (T) [°C] under an air atmosphere. Unless otherwise indicated, the yields [%] were deter-
1
mined by H NMR spectroscopy using an internal standard. [b] Combined yield of 4a and 4aЈ. In parentheses, 4a/4aЈ ratio. [c] Isolated
yield. Where indicated, the values for the other products were estimated using this yield in combination with the crude ratios measured
by 1H NMR spectroscopy. [d] Detected by 1H NMR spectroscopy in the crude product but not quantified. [e] Isoindolone 7a[13] was
obtained (69% in entry 4, 7% in entry 7).
6264
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 6263–6271

Regioselective 5-exo-O-Cyclization/Oxidative Heck Cascades
product 6a was also observed. The preparation of products minor (Յ10%) side-products, and the oxidative dimeriza-
of type 6 from o-alkynylbenzamides 1 has recently been re- tion products related to 6 were absent in most cases. The
ported in the literature under the combined action of cata- standard conditions were found to be efficient, with just
lytic PdII and CuII.[5] Not surprisingly, Pd(OAc)2/PPh3, two exceptions that needed some degree of adjustment. One
without added acetate anion, triggered a very predominant was the case of alkyl/alkyl substitution at R1 and R2 (sub-
5-exo-cyclization (Table 1, entry 8), with an overall exo/endo strate 1b), which gave a comparatively low regioselectivity.
ratio of 91:9 (including the formation of 6a). However, sim- Thus, under the standard conditions, a 61:39 4b/5b ratio
ilar use of Pd(TFA)2/PPh3 (TFA = trifluoroacetate) gave was obtained. However, this improved to 83:17 when
almost no change relative to PdCl2(PPh3)2 (Table 1, entry 9, K2CO3 (10 mol-%) was used as additive with a PdCl2-
exo/endo = 2:98). It was found that the use of small (PPh3)2 precatalyst (Table 2, entry 2). A different problem
amounts of DMAP (4-dimethylaminopyridine) improved was found with Ph/Ph substituted analog 1i, which showed
the 4a/5a ratio and, in combination with an increase in the a high tendency towards cycloisomerization under the stan-
amount of alkene, also resulted in the formation of smaller dard conditions. As a result, 4i was produced in only 27%
amounts of dimer 6a (Table 1, entry 10). Finally, a reason- yield, and an isoindolone 7b[14] (Figure 1) was obtained as
able compromise between the different selectivities at play the major product (57%, E/Z = 23:77). In this case, the
was reached by using 20 equiv. of alkene with just 1 mol-% competing cycloisomerization was completely suppressed
of DMAP at 35 °C (Table 1, entry 11). Under these condi- by using KOBz (10 mol-%) in combination with
tions, 4a was isolated in 73% yield (see also Table 2, en- PdCl2(PPh3)2, and the desired product (i.e., 4i) was ob-
try 1).
tained in 71% yield (Table 2, entry 11). The same condi-
tions were also used with substrate 1j, with a similar result
(Table 2, entry 12).
Table 2. 5-exo-Selective oxidative oxycyclization/coupling reactions
of o-alkynylbenzamides and electron-deficient alkenes.[a]
Entry
1
R1, R2, R3, R4
Y
t
4, yield exo/endo
[h] [%][b] ratio[c]
Figure 1. Cycloisomerization and oxidative dimerization products
obtained in the reactions of 1.
1
1a nBu, Ph, H, H
CO2Et 29 4a, 73 94:6[d]
CO2Et 20 4b, 77 83:17
CO2Et 21 4ca, 80 94:6
COMe 17 4cb, 87 92:8
CO2Et 23 4d, 68 90:10
CO2Et 19 4e, 80 89:11
2[e]
3
1b nBu, nHex, H, H
1c Ph, nHex, H, H
1c Ph, nHex, H, H
1d Ph, nHex, Cl, H
1e Ph, nHex, MeO, MeO
1f pClC6H4, nHex, H, H
1g pMeOC6H4, nHex, H, H CO2Et 21 4ga, 89 93:7
1g pMeOC6H4, nHex, H, H COMe 17 4gb, 80 90:10
1h pCNC6H4, nHex, H, H
1i Ph, Ph, H, H
Next, the generality of the 5-exo-O-cyclization/Heck cou-
pling cascade was studied with a representative set of o-
alkynylbenzamides 1 and electron-deficient alkenes, using
the conditions of Table 1, entry 11 as standard. These re-
sults are collected in Table 2. The effect of the structure of
substrate 1 was probed by introducing all of the four pos-
sible combinations of alkyl- and aryl-type substituents at
R1 and R2, located at the carboxamide amino group and
the terminal alkyne position, respectively (Table 2, en-
tries 1–3, 7–8, and 10–13). Additional substitution with
either electron-donating (OMe) or electron-withdrawing
(Cl) groups was made on the benzamide aryl ring of sub-
strates 1 (Table 2, entries 5 and 6). Besides ethyl acrylate,
the use of methyl vinyl ketone as the alkene partner is also
4
5
6
7
8
9
10
11[f]
12[f]
13
CO2Et 19 4f, 84
94:6
CO2Et 24 4h, 85 91:9
[g]
CO2Et 29 4i, 71
CO2Et 24 4j, 69
1j pMeOC6H4, Ph, H, H
1k Ph, pMeOC6H4, H, H
97:3[h]
CO2Et 26 4k, 70 93:7
[a] Reaction conditions: Unless otherwise indicated, a solution of 1,
Pd(OAc)2 (5 mol-% relative to 1), PPh3 (10 mol-%), KI (0.5 equiv.),
DMAP (1 mol-%), and ethyl acrylate (20 equiv.) in DMF (8.5 mL/
mmol) was heated at 35 °C for the given time (t) [h] under an air
atmosphere. [b] Yield [%] of purified product. [c] Ratio measured
in the crude product. [d] Dimeric product 6a obtained in 18% yield.
illustrated (Table 2, entries 4 and 9). Interestingly, the two [e] Reaction run with PdCl2(PPh3)2 as catalyst and K2CO3 (10 mol-
%) instead of DMAP. [f] Reaction run with PdCl2(PPh3)2 as cata-
reactions with methyl vinyl ketone took place without com-
lyst and KOBz (10 mol-%) instead of DMAP. [g] No endo product
plications arising from competing hydroarylation pro-
was found. Dimeric product 6b[5] obtained in 8% yield. [h] Dimeric
cesses.[8] In all cases, the expected products 4 were obtained
in preparatively useful isolated yields with high regio- and
stereoselectivities. Thus, the indicated diene stereoisomer
product 6c[5] obtained in 8% yield.
The imino functionality of imidates 4 can be hydrolyzed
was formed almost exclusively, with traces of other isomers under acidic conditions,[5,15] as exemplified by the conver-
being observed in the crude product but not isolated. The sion of 4e and 4i into the corresponding lactones 8 in
alternative 6-endo regioisomers 5 were usually obtained as high yields (Scheme 2). As a result, a two-step route to 3-
Eur. J. Org. Chem. 2014, 6263–6271
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6265

Y. Madich, R. Álvarez, J. M. Aurrecoechea
FULL PAPER
allylideneisobenzofuranones appears to be established, able tool, as it provides new synthetic options for structure
using o-alkynylbenzamides as starting materials. The prepa- diversification from a common set of starting materials.
ration of related derivatives has been described using rather
more elaborate routes involving, for example, a metal-
mediated cycloisomerization of appropriately o-substituted
benzoic acids,[16] or, alternatively, metal-catalyzed cross-
coupling reactions of 3-(3-tributylstannylmethylene)iso-
benzofuran-1(3H)-ones.[17,18]
Scheme 2. Hydrolysis of imidates 4.
The synthesis of cyclic imidate derivatives related to 4
Scheme 3. Expected catalytic cycle for the oxycyclization/oxidative
has been reported only in the case where Y = Ar. In that
instance, a two-step parallel synthesis was used, where o-
alkynylbenzamides were first subjected to iodocyclization,
and then the resulting 3-iodomethylene-type products
underwent a Heck coupling with styrenes.[19] In compari-
son, the method reported here for the preparation of prod-
ucts 4 featuring a carbonyl-type Y substituent takes place
directly in a one-pot cascade process, starting from o-alk-
ynylbenzamides and electron-deficient alkenes. Interest-
ingly, the success of this new reaction relies on an appropri-
ate choice of catalyst and/or additives. Thus, comparison
between Table 1, entries 1 and 5–8 indicates that the very
strong preference of the PdCl2(PPh3)2 catalyst for a 6-endo-
vs. a 5-exo-cyclization is reversed either by adding 10 mol-
% of NaOAc or K2CO3 (Table 1, entries 6 and 7) or simply
by changing the Pd counterion from Cl to OAc (Table 1,
entry 8). However, the reasons for this change in the regio-
chemistry of the cyclization remain elusive. Upon addition
of KOBz, NaOAc, or K2CO3 (Table 1, entries 5–7) to the
endo-selective catalyst PdCl2(PPh3)2, the exo/endo ratio in-
creases in the order KOBz Ͻ NaOAc Ͻ K2CO3. This, to-
gether with a comparison between the effect of Pd(OAc)2
(Table 1, entry 8) and the endo-selective Pd(TFA)2 (Table 1,
entry 9), seem to point towards the basicity of the anion as
a determining factor for the regiochemistry. In any case,
the oxidative cascade is likely to proceed through the same
Heck coupling.
Conclusions
A regioselectivity switch between 6-endo- and 5-exo-dig-
cyclization in palladium-catalyzed oxidative cyclization/
Heck-type coupling cascades of o-alkynylbenzamides and
electron-deficient alkenes is triggered by a change in the
palladium catalyst or by the addition of a suitable base
(acetate, benzoate, or carbonate). Reaction conditions have
been found that allow the efficient preparation of 3-methyl-
eneisobenzofuran-1(3H)-imine derivatives incorporating the
electron-deficient alkene carbon unit as additional substitu-
ent. The conversion into the corresponding isobenzofur-
anones by selective hydrolysis of the imino functionality has
been demonstrated in selected cases.
Experimental Section
General Methods: All reactions involving air- and moisture-sensi-
tive materials were carried out under an atmosphere of dry Ar.
Triethylamine and toluene were distilled from CaH2 and purged
with Ar. Commercially sourced DMF (Ն99.8%) was kept over mo-
lecular sieves (4 Å). Flash column chromatography was carried out
using silica gel (230–400 mesh). Routine NMR spectra were ob-
catalytic cycle as other related palladium-catalyzed hetero- tained at 25 °C with a Bruker AV-300 spectrometer (300 MHz for
1H, and 75.4 MHz for 13C) or a Bruker AV-500 spectrometer
cyclization/Heck-type coupling cascades, comprising PdII-
promoted O-cyclization, carbopalladation, β-H elimination,
and Pd0 to PdII oxidation (Scheme 3).[8] In this general
scheme, a base could conceivably participate in the cycliza-
tion step through an interaction with the N–H bond[20] or,
alternatively, have an effect on the equilibrium positions of
the various steps of the catalytic cycle involving release of
acid. Whatever the actual reasons, this kind of catalyst-con-
trolled regiochemical change, while still relatively uncom-
1
(500 MHz for H, and 125.7 MHz for 13C), using CDCl3 or [D6]-
acetone as solvent and internal reference (CDCl3 δ = 7.26 ppm for
1H, and δ = 77.0 ppm for 13C; [D6]acetone δ = 2.05 ppm for 1H,
and δ = 29.84 ppm for 13C). Coupling constants (J) are given in
Hertz (Hz). The DEPT sequence was routinely used for 13C multi-
plicity assignment. Infrared spectra (IR) data were obtained from
a thin film deposited onto a NaCl plate, and were measured with
a Jasco FTIR 4100 instrument in the interval between 4000 and
600 cm–1 with a 4 cm–1 resolution; only characteristic absorptions
mon in metal-catalyzed reactions,[21] is nevertheless a desir- are listed. Electron impact (EI) mass spectra were obtained with a
6266
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 6263–6271

Regioselective 5-exo-O-Cyclization/Oxidative Heck Cascades
Hewlett–Packard HP59970 instrument operating at 70 eV. Chemi-
cal ionization mass spectra were acquired with an Agilent 6890N
gas chromatograph coupled to a mass spectrometer with a Micro-
mass GCT time of flight (TOF) analyzer. Melting points were mea-
sured with a Büchi B-540 apparatus in open capillary tubes. New
compounds were fully characterized by their 1H and 13C NMR,
IR, and HRMS spectral properties. Additionally, for products 4,
the use of 2D NMR correlations (COSY, HSQC, HMBC, and
NOESY) allowed us to differentiate between the different re-
gioisomeric possibilities. Structural assignments were confirmed by
X-Ray analysis of product 4f (Figure S1, Supporting Infor-
mation).[22]
(%) = 376 (100) [M + H]+, 375 (42), 374 (11). HRMS (CI): calcd.
for C24H26NO3 [M + H]+ 376.1913; found 376.1909.
1
Data for 6a: Yellow solid, m.p. 129–131 °C. H NMR (300 MHz,
CDCl3): δ = 1.01 (t, J = 7.3 Hz, 3 H), 1.49–1.61 (m, 2 H), 1.76–
1.86 (m, 2 H), 3.74–3.89 (m, 2 H), 7.22–7.38 (m, 5 H), 7.55 (t, J =
7.7 Hz, 1 H), 7.83 (d, J = 7.5 Hz, 1 H), 7.91 (d, J = 7.5 Hz, 2 H)
ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.0 (CH3), 20.8 (CH2),
33.0 (CH2), 48.3 (CH2), 113.2 (C), 122.8 (CH), 123.5 (CH), 127.7
(CH), 128.5 (2 CH), 129.3 (2 CH), 129.7 (CH), 130.5 (C), 131.9
(CH), 135.8 (C), 136.3 (C), 148.5 (C), 154.5 (C) ppm. IR (film): ν
˜
= 1702 (s), 1610 (m) cm–1. MS (CI): m/z (%) = 553 (100) [M +
H]+, 552 (58), 551 (13). HRMS (CI): calcd. for C38H37N2O2 [M +
H]+ 553.2855; found 553.2845.
Representative Procedure for 5-exo-Heterocyclization/Intermolecular
Heck Coupling Cascades: A solution of 1 (0.235 mmol), Pd(OAc)2
(2.6 mg, 12 μmol), PPh3 (6.2 mg, 23 μmol), KI (19 mg, 0.12 mmol),
DMAP (290 μg, 2.3 μmol), and an electron-deficient alkene
(4.70 mmol) in DMF (2 mL) was stirred at 35 °C for the time indi-
cated in Table 2. The mixture was cooled to 25 °C, then saturated
NaHCO3 solution (4 mL) was added. The mixture was extracted
with EtOAc (3ϫ 8 mL), the combined organic layers were dried
(Na2SO4), and the solvent was removed. The residue was purified
by flash chromatography (silica gel saturated with Et3N, mixtures
of hexanes/EtOAc/Et3N) to give the products indicated in Table 2.
Additional preparation and characterization details are given be-
low.
Ethyl (E)-4-[(1E,3Z)-3-(Butylimino)isobenzofuran-1(3H)-ylidene]-
dec-2-enoate (4b): Prepared from 1b (33.5 mg, 0.117 mmol) and
ethyl acrylate (255 μL, 2.34 mmol), using PdCl2(PPh3)2 (5 mol-%)
as catalyst, and K2CO3 (10 mol-%) instead of DMAP. The crude
mixture was purified by flash chromatography (silica gel saturated
with Et3N, hexanes/EtOAc/Et3N, 98:1:1 to 95:4:1) to give 5b[10]
(7.3 mg, 16%) and 4b (34.4 mg, 77%).
Data for 4b: Yellow oil. 1H NMR (300 MHz, CDCl3): δ = 0.86–
0.90 (m, 3 H), 0.96 (t, J = 7.3 Hz, 3 H), 1.25–1.48 (m, 11 H), 1.51–
1.60 (m, 2 H), 1.65–1.75 (m, 2 H), 2.56–2.62 (m, 2 H), 3.66 (t, J =
7.1 Hz, 2 H), 4.27 (q, J = 7.1 Hz, 2 H), 6.11 (d, J = 15.4 Hz, 1 H),
7.47 (t, J = 7.5 Hz, 1 H), 7.55–7.60 (m, 1 H), 7.88 (d, J = 7.6 Hz,
1 H), 7.97 (d, J = 8.0 Hz, 1 H), 8.28 (d, J = 15.4 Hz, 1 H) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 13.9 (CH3), 14.0 (CH3), 14.3
(CH3), 20.7 (CH2), 22.6 (CH2), 27.3 (CH2), 28.6 (CH2), 29.4 (CH2),
31.6 (CH2), 32.9 (CH2), 47.8 (CH2), 60.4 (CH2), 118.0 (CH, C),
123.3 (CH), 124.2 (CH), 129.7 (CH), 131.7 (C), 131.9 (CH), 134.8
Ethyl (E)-4-[(1Z,3Z)-3-(Butylimino)isobenzofuran-1(3H)-ylidene]-4-
phenylbut-2-enoate (4a), Ethyl (E)-4-[(1E,3Z)-3-(Butylimino)iso-
benzofuran-1(3H)-ylidene]-4-phenylbut-2-enoate (4aЈ), and
(1Z,1ЈZ,3E,3ЈE)-3,3Ј-(1,2-Diphenylethane-1,2-diylidene)bis[N-but-
ylisobenzofuran-1(3H)-imine] (6a): Prepared from 1a[23] (65 mg,
0.23 mmol) and ethyl acrylate (510 μL, 4.68 mmol). The crude mix-
ture was purified by flash chromatography (silica gel saturated with
Et3N, hexanes/EtOAc/Et3N, 98:1:1 to 84:15:1) to give 5a[8] (4.4 mg,
5%), 4a (64 mg, 73%), and 6a (11.7 mg, 18%). Compound 4aЈ was
also detected in the crude product.
(C), 139.8 (CH), 151.7 (C), 153.7 (C), 167.4 (C) ppm. IR (film): ν
˜
= 1704 (s), 1613 (s) cm–1. MS (CI): m/z (%) = 384 (100) [M +
H]+, 383 (20), 382 (23), 340 (11), 338 (10), 312 (12), 300 (15), 299
(67). HRMS (CI): calcd. for C24H34NO3 [M + H]+ 384.2539; found
384.2524.
Ethyl (E)-4-[(1E,3Z)-3-(Phenylimino)isobenzofuran-1(3H)-ylidene]-
dec-2-enoate (4ca): Prepared from 1c[24] (72 mg, 0.24 mmol) and
ethyl acrylate (515 μL, 4.72 mmol). The crude mixture was purified
by flash chromatography (silica gel saturated with Et3N, hexanes/
EtOAc/Et3N, 98:1:1 to 93:6:1) to give 5ca[8] (5 mg, 5%) and 4ca
(77 mg, 80%).
Data for 4ca: Yellow solid, m.p. 70–72 °C. 1H NMR (300 MHz,
[D6]acetone): δ = 0.90 (t, J = 6.9 Hz, 3 H), 1.32–1.46 (m, 9 H),
1.56–1.66 (m, 2 H), 2.61–2.66 (m, 2 H), 4.27 (q, J = 7.1 Hz, 2 H),
6.25 (d, J = 15.4 Hz, 1 H), 7.20–7.25 (m, 1 H), 7.41–7.51 (m, 4 H),
7.69–7.75 (m, 1 H), 7.83–7.88 (m, 1 H), 8.06 (d, J = 8.4 Hz, 2 H),
8.29 (d, J = 15.4 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ
= 14.0 (CH3), 14.3 (CH3), 22.6 (CH2), 27.6 (CH2), 28.9 (CH2), 29.5
(CH2), 31.5 (CH2), 60.5 (CH2), 118.9 (CH), 119.6 (C), 124.0 (CH),
124.1 (CH), 124.2 (2 CH), 125.0 (CH), 128.7 (2 CH), 129.9 (CH),
132.0 (C), 132.5 (CH), 134.5 (C), 139.3 (CH), 145.2 (C), 151.7 (C),
Data for 4a: Yellow solid, m.p. 59–61 °C. 1H NMR (300 MHz,
CDCl3): δ = 0.83 (t, J = 7.3 Hz, 3 H), 1.22–1.33 (m, 5 H), 1.49–
1.59 (m, 2 H), 3.37 (t, J = 7.1 Hz, 2 H), 4.24 (q, J = 7.1 Hz, 2 H),
5.80 (d, J = 15.2 Hz, 1 H), 7.32–7.46 (m, 5 H), 7.55 (t, J = 7.4 Hz,
1 H), 7.63–7.68 (m, 1 H), 7.91 (d, J = 7.5 Hz, 1 H), 8.10 (d, J =
7.9 Hz, 1 H), 8.47 (d, J = 15.2 Hz, 1 H) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 13.7 (CH3), 14.3 (CH3), 20.5 (CH2), 32.7 (CH2), 47.8
(CH2), 60.4 (CH2), 118.4 (C), 121.6 (CH), 123.4 (CH), 124.5 (CH),
127.8 (CH), 128.2 (2 CH), 130.0 (2 CH), 130.4 (CH), 131.9 (C),
132.0 (CH), 135.0 (C), 135.1 (C), 140.5 (CH), 150.9 (C), 153.6 (C),
167.3 (C) ppm. IR (film): ν = 1704 (s), 1611 (s), 1597 (m) cm–1.
˜
MS (CI): m/z (%) = 376 (100) [M + H]+, 375 (20). HRMS (CI):
calcd. for C24H26NO3 [M + H]+ 376.1913; found 376.1904.
Data for 4aЈ (obtained as a by-product in the reactions of 1a; see
1
Table 1): White solid, m.p. 100–102 °C. H NMR (300 MHz, [D6]-
152.5 (C), 167.3 (C) ppm. IR (film): ν = 1704 (s), 1685 (s), 1610
˜
acetone): δ = 1.01 (t, J = 7.3 Hz, 3 H), 1.23 (t, J = 7.1 Hz, 3 H),
1.45–1.57 (m, 2 H), 1.69–1.78 (m, 2 H), 3.77 (t, J = 6.7 Hz, 2 H),
4.15 (q, J = 7.0 Hz, 2 H), 5.40 (d, J = 15.5 Hz, 1 H), 6.22 (d, J =
7.9 Hz, 1 H), 7.32 (t, J = 7.5 Hz, 1 H), 7.35–7.42 (m, 2 H), 7.49–
(s), 1591 (s) cm–1. MS (CI): m/z (%) = 404 (100) [M + H]+, 403
(21), 358 (10), 320 (11), 319 (40), 246 (16). HRMS (CI): calcd. for
C26H30NO3 [M + H]+ 404.2226; found 404.2206.
7.54 (m, 1 H), 7.57–7.65 (m, 3 H), 7.82 (d, J = 7.5 Hz, 1 H), 8.47 (E)-5-[(1E,3Z)-3-(Phenylimino)isobenzofuran-1(3H)-ylidene]undec-
(d, J = 15.5 Hz, 1 H) ppm. 13C NMR (75.5 MHz, [D6]acetone): δ
3-en-2-one (4cb) and (E)-4-[(Z)-3-Hexyl-1-(phenylimino)-1H-iso-
= 14.2 (CH3), 14.5 (CH3), 21.3 (CH2), 33.8 (CH2), 48.2 (CH2), 60.7 chromen-4-yl]but-3-en-2-one (5cb): Prepared from 1c[24] (72 mg,
(CH2), 117.2 (C), 121.0 (CH), 123.7 (CH), 124.6 (CH), 129.7 (CH),
130.4 (2 CH), 131.3 (2 CH), 131.6 (CH), 132.3 (CH), 132.6 (C),
0.24 mmol) and methyl vinyl ketone (383 μL, 4.72 mmol). The
crude mixture was purified by flash chromatography (silica gel sat-
135.0 (C), 135.9 (C), 141.0 (CH), 151.1 (C), 153.0 (C), 166.9 (C) urated with Et3N, hexanes/EtOAc/Et3N, 95:4:1 to 79:20:1) to give
ppm. IR (film): ν = 1706 (s), 1613 (s), 1595 (m) cm–1. MS (CI): m/z
5cb (6.2 mg, 7%) and 4cb (77 mg, 87%).
˜
Eur. J. Org. Chem. 2014, 6263–6271
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6267

Y. Madich, R. Álvarez, J. M. Aurrecoechea
FULL PAPER
Data for 4cb: Yellow-brown solid, m.p. 54–56 °C. 1H NMR
7.1 Hz, 2 H), 6.10 (d, J = 15.4 Hz, 1 H), 7.16 (tt, J = 7.0, 1.6 Hz,
(300 MHz, CDCl3): δ = 0.86–0.91 (m, 3 H), 1.26–1.41 (m, 6 H), 1 H), 7.34–7.43 (m, 6 H), 8.22 (d, J = 15.4 Hz, 1 H) ppm. 13C
1.49–1.59 (m, 2 H), 2.39 (s, 3 H), 2.53–2.58 (m, 2 H), 6.47 (d, J =
15.5 Hz, 1 H), 7.16–7.21 (m, 1 H), 7.36–7.46 (m, 4 H), 7.58 (t, J =
7.5 Hz, 1 H), 7.65–7.70 (m, 1 H), 7.99 (d, J = 8.0 Hz, 1 H), 8.07
(d, J = 7.6 Hz, 1 H), 8.16 (d, J = 15.5 Hz, 1 H) ppm. 13C NMR
NMR (75.5 MHz, CDCl3): δ = 14.0 (CH3), 14.3 (CH3), 22.6 (CH2),
27.4 (CH2), 28.9 (CH2), 29.5 (CH2), 31.5 (CH2), 56.2 (CH3), 56.4
(CH3), 60.4 (CH2), 104.5 (CH), 105.1 (CH), 117.9 (C), 118.0 (CH),
124.2 (2 CH), 124.8 (CH), 125.5 (C), 128.2 (C), 128.6 (2 CH), 139.6
(300 MHz, CDCl3): δ = 14.0 (CH3), 22.6 (CH2), 27.6 (CH2), 28.6 (CH), 145.4 (C), 151.5 (C), 151.8 (C), 152.8 (C), 153.2 (C), 167.3
(CH3), 28.9 (CH2), 29.5 (CH2), 31.5 (CH2), 119.9 (C), 124.1 (2 CH), (C) ppm. IR (film): ν = 1738 (m), 1705 (s), 1679 (s), 1597 (s), 1500
˜
124.2 (2 CH), 125.1 (CH), 127.1 (CH), 128.7 (2 CH), 130.1 (CH),
132.1 (C), 132.6 (CH), 134.4 (C), 137.8 (CH), 145.2 (C), 152.3 (C), (12), 334 (39), 333 (26), 332 (14), 318 (14), 307 (30), 306 (74), 305
(s) cm–1. MS (EI): m/z (%) = 463 (8) [M]+, 380 (22), 379 (100), 346
152.4 (C), 197.5 (C) ppm. IR (film): ν = 1683 (s), 1667 (s), 1608
(20), 295 (10), 294 (39), 292 (17), 290 (18). HRMS (EI): calcd. for
˜
(m), 1577 (s) cm–1. MS (EI): m/z (%) = 373 (27) [M]+, 302 (32), 289 C28H33NO5 [M]+ 463.2359; found 463.2358.
(16), 288 (100), 274 (11), 272 (13), 260 (23), 259 (12), 258 (22), 248
Ethyl (E)-4-{(1E,3Z)-3-[(4-Chlorophenyl)imino]isobenzofuran-
(17), 246 (34), 245 (11), 234 (17), 232 (24), 230 (18), 217 (13), 197
(17), 179 (15), 77 (12). HRMS (EI): calcd. for C25H27NO2 [M]+
373.2042; found 373.2044.
1(3H)-ylidene}dec-2-enoate (4f): Prepared from 1f (80 mg,
0.235 mmol) and ethyl acrylate (513 μL, 4.70 mmol). The crude
mixture was purified by flash chromatography (silica gel saturated
with Et3N, hexanes/EtOAc/Et3N, 97:2:1 to 91:8:1) to give 5f[10]
(8 mg, 8%) and 4f (87 mg, 84%).
1
Data for 5cb: Yellow oil. H NMR (300 MHz, CDCl3): δ = 0.84–
0.89 (m, 3 H), 1.17–1.30 (m, 6 H), 1.48–1.55 (m, 2 H), 2.40 (s, 3
H), 2.50 (t, J = 7.4 Hz, 2 H), 6.46 (d, J = 16.2 Hz, 1 H), 7.08–7.16
(m, 3 H), 7.32–7.37 (m, 2 H), 7.41–7.59 (m, 4 H), 8.41 (d, J =
7.6 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.0 (CH3),
22.4 (CH2), 27.3 (CH2), 28.0 (CH3), 28.6 (CH2), 31.1 (CH2), 31.4
(CH2), 109.5 (C), 122.5 (2 CH), 122.9 (CH), 123.3 (C), 123.7 (CH),
127.8 (CH), 128.0 (CH), 128.6 (2 CH), 132.4 (CH), 132.6 (C), 132.8
(CH), 136.7 (CH), 146.3 (C), 148.7 (C), 156.1 (C), 197.6 (C) ppm.
Data for 4f: Yellow solid, m.p. 110–112 °C. 1H NMR (300 MHz,
[D6]acetone): δ = 0.91 (t, J = 6.9 Hz, 3 H), 1.30–1.47 (m, 9 H),
1.56–1.66 (m, 2 H), 2.63–2.68 (m, 2 H), 4.28 (q, J = 7.1 Hz, 2 H),
6.28 (d, J = 15.4 Hz, 1 H), 7.43–7.51 (m, 4 H), 7.74 (t, J = 7.6 Hz,
1 H), 7.86–7.91 (m, 1 H), 8.05–8.09 (m, 2 H), 8.29 (d, J = 15.4 Hz,
1 H) ppm. 13C NMR (75.5 MHz, [D6]acetone): δ = 14.4 (CH3),
14.6 (CH3), 23.4 (CH2), 28.1 (CH2), 29.6 (CH2), 30.2 (CH2), 32.3
(CH2), 61.0 (CH2), 120.5 (CH), 120.7 (C), 124.9 (2 CH), 126.7 (2
CH), 129.6 (2 CH), 130.6 (C), 131.3 (CH), 132.6 (C), 134.2 (CH),
135.4 (C), 139.4 (CH), 145.3 (C), 152.2 (C), 153.7 (C), 167.2 (C)
IR (film): ν = 1654 (s), 1591 (s) cm–1. MS (EI): m/z (%) = 373 (6)
˜
[M]+, 330 (14), 289 (14), 288 (100), 278 (13), 277 (83), 276 (26), 260
(19), 246 (25), 235 (29), 234 (84), 233 (47), 232 (83), 218 (12), 217
(17), 204 (19), 185 (10). HRMS (EI): calcd. for C25H27NO2 [M]+
373.2042; found 373.2039.
ppm. IR (film): ν = 1711 (s), 1678 (s), 1610 (s), 1579 (m) cm–1. MS
˜
(EI): m/z (%) = 439 (2) [37Cl M]+, 437 (6) [35Cl M]+, 366 (15), 355
Ethyl (E)-4-[(1E,3Z)-6-Chloro-3-(phenylimino)isobenzofuran-1(3H)- (10), 353 (34), 320 (13), 309 (14), 308 (31), 307 (35), 306 (14), 292
ylidene]dec-2-enoate (4d): Prepared from 1d (80 mg, 0.235 mmol)
and ethyl acrylate (513 μL, 4.70 mmol). The crude mixture was
purified by flash chromatography (silica gel saturated with Et3N,
hexanes/EtOAc/Et3N, 98:1:1 to 97:2:1) to give 5d[10] (9.5 mg, 9%)
and 4d (70 mg, 68%).
Data for 4d: Yellow solid, m.p. 92–93 °C. 1H NMR (300 MHz,
[D6]acetone): δ = 0.91 (t, J = 6.9 Hz, 3 H), 1.34–1.47 (m, 9 H),
(15), 282 (24), 281 (21), 280 (100), 279 (22), 278 (13), 268 (23), 266
(18), 264 (37). HRMS (EI): calcd. for C26H2835ClNO3 [M]+
437.1758; found 437.1763. HRMS (EI): calcd. for C26H2837ClNO3
[M]+ 439.1728; found 439.1749. The structural assignment was ad-
ditionally confirmed by X-Ray analysis (Figure S1, Supporting In-
formation).
Ethyl (E)-4-{(1E,3Z)-3-[(4-Methoxyphenyl)imino]isobenzofuran-
1.57–1.66 (m, 2 H), 2.63–2.69 (m, 2 H), 4.29 (q, J = 7.1 Hz, 2 H), 1(3H)-ylidene}dec-2-enoate (4ga) and Ethyl (E)-3-{(Z)-3-Hexyl-1-
6.30 (d, J = 15.4 Hz, 1 H), 7.22–7.29 (m, 1 H), 7.42–7.51 (m, 4 H), [(4-methoxyphenyl)imino]-1H-isochromen-4-yl}acrylate (5ga): Pre-
7.75 (dd, J = 8.3, 1.6 Hz, 1 H), 8.01 (s, 1 H), 8.06 (d, J = 8.3 Hz, pared from 1g[24] (79 mg, 0.235 mmol) and ethyl acrylate (513 μL,
1 H), 8.18 (d, J = 15.4 Hz, 1 H) ppm. 13C NMR (75.5 MHz, 4.70 mmol). The crude mixture was purified by flash chromatog-
[D6]acetone): δ = 14.4 (CH3), 14.6 (CH3), 23.4 (CH2), 28.3 (CH2), raphy (silica gel saturated with Et3N, hexanes/EtOAc/Et3N, 97:2:1
29.6 (CH2), 30.2 (CH2), 32.3 (CH2), 61.0 (CH2), 121.0 (CH), 121.6 to 87:12:1) to give 5ga (7 mg, 7%) and 4ga (91 mg, 89%).
(C), 124.6 (CH), 125.3 (2 CH), 126.2 (2 CH), 129.6 (2 CH), 131.4
(CH), 131.6 (C), 136.7 (C), 138.9 (CH), 139.2 (C), 146.0 (C), 151.0
Data for 4ga: Yellow solid, m.p. 79–80 °C. 1H NMR (300 MHz,
[D6]acetone): δ = 0.86–0.91 (m, 3 H), 1.28–1.38 (m, 7 H), 1.42–1.51
(C), 151.8 (C), 167.1 (C) ppm. IR (film): ν = 1710 (s), 1685 (s),
˜
(m, 2 H), 1.57–1.66 (m, 2 H), 2.64–2.69 (m, 2 H), 3.82 (s, 3 H),
4.24 (q, J = 7.1 Hz, 2 H), 6.21 (d, J = 15.4 Hz, 1 H), 6.97 (d, J =
9.0 Hz, 2 H), 7.53 (d, J = 9.0 Hz, 2 H), 7.66 (t, J = 7.3 Hz, 1 H),
7.76–7.82 (m, 1 H), 7.98–8.03 (m, 2 H), 8.27 (d, J = 15.4 Hz, 1 H)
ppm. 13C NMR (75.5 MHz, [D6]acetone): δ = 14.4 (CH3), 14.7
(CH3), 23.4 (CH2), 28.3 (CH2), 29.5 (CH2), 30.3 (CH2), 32.3 (CH2),
55.7 (CH3), 60.9 (CH2), 114.7 (2 CH), 119.7 (C, CH), 124.4 (CH),
1611 (s), 1590 (m) cm–1. MS (EI): m/z (%) = 439 (1) [37Cl M]+, 437
(4) [35Cl M]+, 353 (24), 320 (11), 308 (23), 307 (17), 306 (14), 294
(10), 292 (17), 282 (31), 281 (29), 280 (100), 279 (31), 278 (11), 268
(26), 266 (21). HRMS (EI): calcd. for C26H2835ClNO3 [M]+
437.1758; found 437.1766. HRMS (EI): calcd. for C26H2837ClNO3
[M]+ 439.1728; found 439.1748.
Ethyl (E)-4-[(1E,3Z)-5,6-Dimethoxy-3-(phenylimino)isobenzofuran- 124.7 (CH), 127.4 (2 CH), 131.0 (CH), 133.3 (C), 133.4 (CH), 134.8
1(3H)-ylidene]dec-2-enoate (4e): Prepared from 1e (86 mg, (C), 138.9 (C), 139.6 (CH), 151.2 (C), 152.6 (C), 158.5 (C), 167.3
0.235 mmol) and ethyl acrylate (513 μL, 4.68 mmol). The crude (C) ppm. IR (film): ν = 1705 (s), 1682 (s), 1603 (s), 1505 (s) cm–1.
˜
mixture was purified by flash chromatography (silica gel saturated
MS (CI): m/z (%) = 434 (100) [M + H]+, 433 (64), 349 (47). HRMS
with Et3N, hexanes/EtOAc/Et3N, 96:3:1 to 49:50:1), to give 5e[10] (CI): calcd. for C27H32NO4 [M + H]+ 434.2331; found 434.2317.
(11 mg, 10%) and 4e (87 mg, 80%).
Data for 5ga: Yellow oil. 1H NMR (300 MHz, [D6]acetone): δ =
1
Data for 4e: Yellow solid, m.p. 149–150 °C. H NMR (300 MHz, 0.84–0.88 (m, 3 H), 1.24–1.37 (m, 9 H), 1.63–1.71 (m, 2 H), 2.64–
CDCl3): δ = 0.85–0.90 (m, 3 H), 1.28–1.36 (m, 9 H), 1.48–1.58 (m, 2.69 (m, 2 H), 3.80 (s, 3 H), 4.25 (q, J = 7.1 Hz, 2 H), 6.22 (d, J =
2 H), 2.49–2.54 (m, 2 H), 4.02 (s, 3 H), 4.05 (s, 3 H), 4.26 (q, J = 16.0 Hz, 1 H), 6.92 (d, J = 8.9 Hz, 2 H), 7.25 (d, J = 8.9 Hz, 2 H),
6268
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 6263–6271

Regioselective 5-exo-O-Cyclization/Oxidative Heck Cascades
7.46–7.52 (m, 2 H), 7.62–7.71 (m, 2 H), 8.34 (d, J = 7.1 Hz, 1 H) (75.5 MHz, [D6]acetone): δ = 14.3 (CH3), 14.4 (CH3), 23.3 (CH2),
ppm. 13C NMR (75.5 MHz, [D6]acetone): δ = 14.3 (CH3), 14.6
28.0 (CH2), 29.6 (CH2), 30.1 (CH2), 32.2 (CH2), 61.0 (CH2), 108.6
(CH3), 23.1 (CH2), 28.0 (CH2), 29.3 (CH2), 31.7 (CH2), 32.1 (CH2), (C), 119.6 (C), 121.0 (CH), 121.4 (C), 124.9 (CH), 125.1 (CH),
55.6 (CH3), 61.1 (CH2), 110.3 (C), 114.6 (2 CH), 124.0 (CH), 124.5 125.3 (2 CH), 131.4 (CH), 132.0 (C), 133.8 (2 CH), 134.6 (CH),
(C), 125.3 (2 CH), 125.6 (CH), 128.2 (CH), 128.8 (CH), 133.2 135.6 (C), 139.1 (CH), 151.2 (C), 151.9 (C), 155.0 (C), 167.2 (C)
(CH), 133.5 (C), 138.5 (CH), 140.0 (C), 148.4 (C), 156.6 (C), 157.4 ppm. IR (film): ν = 2224 (w), 1703 (s), 1681 (s), 1613 (s), 1594 (s)
˜
(C), 166.5 (C) ppm. IR (film): ν = 1715 (s), 1652 (s), 1636 (s) cm–1. cm–1. MS (CI): m/z (%) = 429 (100) [M + H]+, 428 (25), 344 (29).
˜
MS (CI): m/z (%) = 434 (90) [M + H]+, 433 (100). HRMS (CI): HRMS (CI): calcd. for C27H29N2O3 [M + H]+ 429.2178; found
calcd. for C27H32NO4 [M + H]+ 434.2331; found 434.2318.
429.2164.
(E)-5-{(1E,3Z)-3-[(4-Methoxyphenyl)imino]isobenzofuran-1(3H)-
ylidene}undec-3-en-2-one (4gb) and (E)-4-[(Z)-3-Hexyl-1-(4-meth-
oxyphenylimino)-1H-isochromen-4-yl]but-3-en-2-one (5gb): Pre-
pared from 1g[24] (79 mg, 0.235 mmol) and methyl vinyl ketone
(381 μL, 4.70 mmol). The crude mixture was purified by flash
Data for 5h: Brown oil. 1H NMR (300 MHz, [D6]acetone): δ =
0.83–0.87 (m, 3 H), 1.23–1.37 (m, 9 H), 1.50–1.57 (m, 2 H), 2.58
(t, J = 7.3 Hz, 2 H), 4.25 (q, J = 7.1 Hz, 2 H), 6.23 (d, J = 16.0 Hz,
1 H), 7.32 (d, J = 7.8 Hz, 2 H), 7.57 (d, J = 7.8 Hz, 2 H), 7.65–
7.77 (m, 4 H), 8.36 (d, J = 7.4 Hz, 1 H) ppm. 13C NMR (75.5 MHz,
chromatography (silica gel saturated with Et3N, hexanes/EtOAc/ [D6]acetone): δ = 14.3 (CH3), 14.6 (CH3), 23.0 (CH2), 27.8 (CH2),
Et3N, 94:5:1 to 74:25:1) to give 5gb (6.6 mg, 7%) and 4gb (76 mg, 29.2 (CH2), 31.5 (CH2), 32.1 (CH2), 61.1 (CH2), 107.3 (C), 110.8
80%).
(C), 119.9 (C), 123.3 (C), 124.2 (CH), 124.3 (CH), 126.3 (CH),
128.6 (CH), 129.1 (CH), 133.8 (2 CH), 134.0 (C), 134.2 (CH), 138.1
Data for 4gb: Yellow-orange solid, m.p. 102–104 °C. 1H NMR
(300 MHz, CDCl3): δ = 0.88–0.92 (m, 3 H), 1.32–1.44 (m, 6 H),
1.56–1.63 (m, 2 H), 2.40 (s, 3 H), 2.59–2.64 (m, 2 H), 3.85 (s, 3 H),
6.47 (d, J = 15.5 Hz, 1 H), 6.93 (d, J = 9.0 Hz, 2 H), 7.52–7.58 (m,
3 H), 7.65 (t, J = 7.5 Hz, 1 H), 7.98 (d, J = 8.0 Hz, 1 H), 8.03 (d,
(CH), 151.1 (C), 152.6 (C), 156.2 (C), 166.3 (C) ppm. IR (film): ν
˜
= 2224 (w), 1715 (s), 1652 (s), 1593 (s) cm–1. MS (CI): m/z (%) =
429 (100) [M + H]+, 428 (53). HRMS (CI): calcd. for C27H29N2O3
[M + H]+ 429.2178; found 429.2159.
J = 7.6 Hz, 1 H), 8.17 (d, J = 15.5 Hz, 1 H) ppm. 13C NMR Ethyl (E)-4-Phenyl-4-[(1Z,3Z)-3-(phenylimino)isobenzofuran-1(3H)-
(75.5 MHz, CDCl3): δ = 14.1 (CH3), 22.7 (CH2), 27.8 (CH2), 28.6 ylidene]but-2-enoate (4i): Prepared from 1i (70 mg, 0.235 mmol)
(CH3), 28.9 (CH2), 29.6 (CH2), 31.6 (CH2), 55.4 (CH3), 113.9 (2 and ethyl acrylate (513 μL, 4.7 mmol), using PdCl2(PPh3)2 (5 mol-
CH), 119.4 (C), 123.9 (CH), 124.0 (CH), 126.4 (2 CH), 126.9 (CH), %) as catalyst, and KOBz (10 mol-%) instead of DMAP. The crude
130.0 (CH), 132.2 (CH), 132.6 (C), 134.1 (C), 138.0 (CH), 151.0
mixture was purified by flash chromatography (silica gel saturated
(C), 152.7 (C), 157.4 (C), 197.6 (C) ppm. IR (film): ν = 1681 (m), with Et3N, hexanes/EtOAc/Et3N, 97:2:1 to 80:19:1), to give 4i
˜
1600 (m), 1573 (s), 1504 (s) cm–1. MS (EI): m/z (%) = 403 (54)
[M]+, 388 (21), 362 (11), 361 (32), 360 (77), 347 (12), 346 (24), 333
(11), 332 (43), 319 (28), 318 (100), 304 (14), 302 (16), 290 (30), 289
(17), 288 (28), 277 (14), 276 (66), 275 (22), 274 (17), 264 (18), 263
(13), 262 (44), 261 (15), 260 (16), 258 (12), 253 (14), 247 (14), 246
(20), 245 (10), 238 (39), 233 (11), 232 (17), 217 (13), 197 (40),
HRMS (EI): calcd. for C26H29NO3 [M]+ 403.2147; found 403.2146.
(66 mg, 71%) and 6b[5] (5.7 mg, 8%).
Data for 4i: Yellow solid, m.p. 143–145 °C. 1H NMR (300 MHz,
[D6]acetone): δ = 1.27 (t, J = 7.1 Hz, 3 H), 4.21 (q, J = 7.1 Hz, 2
H), 5.77 (d, J = 15.3 Hz, 1 H), 7.07 (t, J = 7.2 Hz, 1 H), 7.17–7.22
(m, 2 H), 7.28 (d, J = 7.9 Hz, 2 H), 7.42–7.54 (m, 5 H), 7.78 (t, J
= 7.5 Hz, 1 H), 7.92 (t, J = 7.5 Hz, 1 H), 8.07 (d, J = 7.8 Hz, 1 H),
8.21 (d, J = 7.9 Hz, 1 H), 8.49 (d, J = 15.3 Hz, 1 H) ppm. 13C
Data for 5gb: Yellow solid, m.p. 64–66 °C. 1H NMR (300 MHz, NMR (75.5 MHz, [D6]acetone): δ = 14.6 (CH3), 61.0 (CH2), 120.5
CDCl3): δ = 0.84–0.90 (m, 3 H), 1.20–1.33 (m, 6 H), 1.52–1.62 (m, (C), 123.2 (CH), 124.8 (CH), 125.2 (CH), 125.9 (2 CH), 126.1
2 H), 2.40 (s, 3 H), 2.53 (t, J = 7.5 Hz, 2 H), 3.83 (s, 3 H), 6.46 (d,
(CH), 128.9 (CH), 129.2 (2 CH), 129.3 (2 CH), 131.0 (2 CH), 131.9
J = 16.2 Hz, 1 H), 6.90 (d, J = 8.8 Hz, 2 H), 7.21 (d, J = 8.8 Hz, (CH), 133.2 (C), 134.0 (CH), 135.2 (C), 135.9 (C), 140.4 (CH),
2 H), 7.39–7.44 (m, 2 H), 7.50–7.56 (m, 2 H), 8.39 (d, J = 7.7 Hz, 145.6 (C), 151.9 (C), 152.5 (C), 167.0 (C) ppm. IR (film): ν = 1704
˜
1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.0 (CH3), 22.4 (s), 1681 (s), 1609 (s), 1593 (s) cm–1. MS (CI): m/z (%) = 396 (100)
(CH2), 27.4 (CH2), 27.9 (CH3), 28.6 (CH2), 31.2 (CH2), 31.4 (CH2), [M + H]+, 395 (71), 350 (10), 322 (27), 321 (17). HRMS (CI): calcd.
55.4 (CH3), 109.5 (C), 113.8 (2 CH), 122.8 (CH), 123.7 (C), 124.3 for C26H22NO3 [M + H]+ 396.1600; found 396.1581.
(2 CH), 127.6 (CH), 127.9 (CH), 132.0 (CH), 132.3 (C), 132.6
Ethyl (E)-4-{(1Z,3Z)-3-[(4-Methoxyphenyl)imino]isobenzofuran-
1(3H)-ylidene}-4-phenylbut-2-enoate (4j): Prepared from 1j
(77.0 mg, 0.235 mmol) and ethyl acrylate (513 μL, 4.7 mmol), using
PdCl2(PPh3)2 (5 mol-%) as catalyst, and KOBz (10 mol-%) instead
of DMAP. The crude was purified by flash chromatography (silica
gel saturated with Et3N, hexanes/EtOAc/Et3N, 95:4:1 to 60:39:1),
(CH), 136.8 (CH), 139.0 (C), 147.9 (C), 156.1 (C), 156.2 (C), 197.6
(C) ppm. IR (film): ν = 1693 (m), 1650 (s), 1607 (m), 1504 (s) cm–1.
˜
MS (EI): m/z (%) = 403 (10) [M]+, 360 (15), 319 (15), 318 (100),
290 (16), 276 (16), HRMS (EI): calcd. for C26H29NO3 [M]+
403.2147; found 403.2144.
Ethyl (E)-4-{(1E,3Z)-3-[(4-Cyanophenyl)imino]isobenzofuran-1(3H)- to give 4j (72 mg), 5j[8] (2 mg, 2%), and 6c[5] (5.7 mg, 8%). Product
ylidene}dec-2-enoate (4h) and Ethyl (E)-3-{(Z)-1-[(4-Cyanophenyl)
imino]-3-hexyl-1H-isochromen-4-yl}acrylate (5h): Prepared from 1h
(77 mg, 0.233 mmol) and ethyl acrylate (508 μL, 4.66 mmol). The
crude mixture was purified by flash chromatography (silica gel sat-
urated with Et3N, hexanes/EtOAc/Et3N, 96:3:1 to 87:12:1) to give
5h (8 mg, 8%) and 4h (85 mg, 85%).
4j was further purified by stirring for 16 h at room temperature in
hexanes (5 mL). The solvent was then decanted to give pure 4j
(69 mg, 69%).
Data for 4j: Yellow-orange solid, m.p. 149–151 °C. 1H NMR
(300 MHz, [D6]acetone): δ = 1.27 (t, J = 6.9 Hz, 3 H), 3.76 (s, 3
H), 4.21 (q, J = 6.9 Hz, 2 H), 5.76 (d, J = 15.1 Hz, 1 H), 6.74 (d,
1
Data for 4h: Yellow solid, m.p. 120–122 °C. H NMR (300 MHz, J = 8.3 Hz, 2 H), 7.29 (d, J = 8.5 Hz, 2 H), 7.47–7.56 (m, 5 H),
[D6]acetone): δ = 0.84–0.88 (m, 3 H), 1.26–1.41 (m, 9 H), 1.49–1.59 7.74 (t, J = 7.3 Hz, 1 H), 7.88 (t, J = 7.4 Hz, 1 H), 8.02 (d, J =
(m, 2 H), 2.55–2.60 (m, 2 H), 4.24 (q, J = 7.1 Hz, 2 H), 6.26 (d, J 7.4 Hz, 1 H), 8.18 (d, J = 7.6 Hz, 1 H), 8.49 (d, J = 15.1 Hz, 1 H)
= 15.5 Hz, 1 H), 7.53 (d, J = 8.4 Hz, 2 H), 7.73 (t, J = 7.5 Hz, 1
H), 7.79 (d, J = 8.4 Hz, 2 H), 7.88 (t, J = 7.7 Hz, 1 H), 8.06 (d, J
ppm. 13C NMR (75.5 MHz, [D6]acetone): δ = 14.6 (CH3), 55.6
(CH3), 60.9 (CH2), 114.5 (2 CH), 120.1 (C), 122.8 (CH), 124.6
= 8.2 Hz, 2 H), 8.23 (d, J = 15.5 Hz, 1 H) ppm. 13C NMR (CH), 125.1 (CH), 127.9 (2 CH), 128.9 (CH), 129.3 (2 CH), 131.0
Eur. J. Org. Chem. 2014, 6263–6271
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6269

Y. Madich, R. Álvarez, J. M. Aurrecoechea
FULL PAPER
(2 CH), 131.9 (CH), 133.6 (CH), 134.8 (C), 136.1 (C), 138.4 (C), 166.0 (C), 166.7 (C) ppm. IR (film): ν = 1777 (s), 1707 (s), 1612
˜
140.5 (CH), 150.9 (C), 152.2 (C), 158.7 (C), 167.0 (C) ppm. IR (m) cm–1. MS (CI): m/z (%) = 321 (100) [M + H]+, 320 (71), 276
(film): ν = 1704 (s), 1680 (s), 1605 (s), 1594 (s) cm–1. MS (CI): m/z
(15), 275 (73), 274 (15), 247 (20), 246 (12). HRMS (CI): calcd. for
˜
(%) = 426 (100) [M + H]+, 425 (93), 380 (20), 352 (31), 351 (13). C20H17O4 [M + H]+ 321.1127; found 321.1114.
HRMS (CI): calcd. for C27H24NO4 [M + H]+ 426.1705; found
Supporting Information (see footnote on the first page of this arti-
426.1692.
cle): Preparation and characterization details for compounds 1b,
1
1d, 1e, 1f, 1h, and 1k; ORTEP diagram of 4f; copies of H and 13C
Ethyl (2E,4Z)-4-[(Z)-(4-Methoxyphenyl)-4-(3-phenylimino-3H-iso-
benzofuran-1-ylidene)]but-2-enoate (4k): Prepared from 1k (77 mg,
0.235 mmol) and ethyl acrylate (513 μL, 4.70 mmol). The crude
mixture was purified by flash chromatography (silica gel saturated
with Et3N, hexanes/EtOAc/Et3N, 90:9:1 to 70:29:1) to give 5k[10]
(4 mg, 4%) and 4k (70 mg, 70%).
NMR spectra for all new compounds.
Acknowledgments
The authors thank the Spanish Ministerio de Economía y Compet-
itividad (MEC) (FEDER, grant number CTQ2012-37734) and the
Universidad del País Vasco (fellowship to Y. M.) for financial sup-
port. Servicios Generales de Investigación (SGIker, Universidad del
País Vasco) is thanked for technical support (NMR facilities,
HRMS, and X-ray analysis).
1
Data for 4k: Yellow solid, m.p. 139–141 °C. H NMR (300 MHz,
[D6]acetone): δ = 1.31 (t, J = 7.1 Hz, 3 H), 3.92 (s, 3 H), 4.25 (q, J
= 7.1 Hz, 2 H), 5.87 (d, J = 15.2 Hz, 1 H), 7.08–7.18 (m, 3 H),
7.24–7.29 (m, 2 H), 7.34–7.37 (m, 2 H), 7.43 (d, J = 8.8 Hz, 2 H),
7.78 (t, J = 7.5 Hz, 1 H), 7.90–7.95 (m, 1 H), 8.09 (d, J = 7.7 Hz,
1 H), 8.19 (d, J = 8.0 Hz, 1 H), 8.49 (d, J = 15.2 Hz, 1 H) ppm.
13C NMR (75.5 MHz, [D6]acetone): δ = 14.6 (CH3), 55.7 (CH3),
60.9 (CH2), 114.5 (2 CH), 120.3 (C), 123.3 (CH), 124.8 (CH), 125.1
(CH), 125.8 (2 CH), 126.1 (CH), 127.8 (C), 129.3 (2 CH), 131.7
(CH), 132.4 (2 CH), 133.1 (C), 133.9 (CH), 135.4 (C), 140.8 (CH),
145.7 (C), 151.7 (C), 152.7 (C), 160.6 (C), 167.0 (C) ppm. IR (film)
[1] a) B. Godoi, R. F. Schumacher, G. Zeni, Chem. Rev. 2011, 111,
2937–2980; b) X. M. Zeng, Chem. Rev. 2013, 113, 6864–6900.
[2] H. V. Adcock, P. W. Davies, Synthesis 2012, 44, 3401–3420.
[3] K. Gilmore, I. V. Alabugin, Chem. Rev. 2011, 111, 6513–6556.
[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.
ν 1694 (s), 1679 (s), 1602 (s), 1587 (s), 1509 (s) cm–1. MS (CI): m/z
˜
(%) = 426 (100) [M + H]+, 425 (61), 352 (11). HRMS (CI): calcd.
for C27H24NO4 [M + H]+ 426.1705; found 426.1689.
[5] B. Yao, C. Jaccoud, Q. Wang, J. Zhu, Chem. Eur. J. 2012, 18,
5864–5868.
[6] B. Yao, Q. Wang, J. Zhu, Angew. Chem. Int. Ed. 2013, 52,
12992–12996; Angew. Chem. 2013, 125, 13230–13234.
[7] R. Mancuso, I. Ziccarelli, D. Armentano, N. Marino, S. V.
Giofrè, B. Gabriele, J. Org. Chem. 2014, 79, 3506–3518.
[8] a) R. Álvarez, C. Martínez, Y. Madich, J. G. Denis, J. M. Aur-
recoechea, Á. R. de Lera, Chem. Eur. J. 2010, 16, 12746–12753;
b) R. Álvarez, C. Martínez, Y. Madich, J. G. Denis, J. M. Aur-
recoechea, Á. R. de Lera, Chem. Eur. J. 2012, 18, 13894–13896.
[9] a) C. Martínez, J. M. Aurrecoechea, Y. Madich, J. G. Denis,
Á. R. de Lera, R. Álvarez, Eur. J. Org. Chem. 2012, 99–106; b)
C. Martínez, J. M. Aurrecoechea, Y. Madich, J. G. Denis, A. R.
de Lera, R. Álvarez, Eur. J. Org. Chem. 2012, 6291–6292.
[10] Y. Madich, J. G. Denis, A. Ortega, C. Martinez, A. Matrane,
L. Belachemi, A. R. de Lera, R. Álvarez, J. M. Aurrecoechea,
Synthesis 2013, 45, 2009–2017.
[11] a) C. Schlemmer, L. Andernach, D. Schollmeyer, B. F. Straub,
T. Opatz, J. Org. Chem. 2012, 77, 10118–10124; b) S. Mehta,
T. Yao, R. C. Larock, J. Org. Chem. 2012, 77, 10938–10944; c)
K. Bert, T. Noel, W. Kimpe, J. L. Goeman, J. Van der Eycken,
Org. Biomol. Chem. 2012, 10, 8539–8550.
[12] a) C. Kanazawa, M. Terada, Tetrahedron Lett. 2007, 48, 933–
935; b) A one-pot Sonogashira/cycloisomerization sequence
performed in the presence of DBU also leads to N-cyclization.
It is likely that this cyclization is also a Brönsted-base/
Brönsted-acid-promoted process: S. Sarkar, S. Dutta, R. Dey,
S. Naskar, Tetrahedron Lett. 2012, 53, 6789–6792.
Ethyl (E)-4-[(E)-5,6-Dimethoxy-3-oxoisobenzofuran-1(3H)-ylidene]-
dec-2-enoate (8a): HCl (37% aq.; 12 μL, 0.145 mmol) was added to
a solution of 4e (27.0 mg, 0.058 mmol) in THF (1.2 mL), and the
mixture was stirred for 2 h at room temperature. The mixture was
diluted with brine (5 mL), and extracted with CH2Cl2 (3ϫ 4 mL).
The combined organic extracts were washed with saturated
NaHCO3 solution (1 mL) and water (1 mL), and dried (Na2SO4).
The crude mixture was purified by flash chromatography (silica gel
saturated with Et3N, hexanes/EtOAc/Et3N, 94:5:1 to 84:15:1), to
give 8a (20.3 mg, 90 %) as a yellow solid, m.p. 136–137 °C. 1H
NMR (300 MHz, CDCl3): δ = 0.89 (t, J = 6.6 Hz, 3 H), 1.25–1.41
(m, 9 H), 1.50–1.60 (m, 2 H), 2.60–2.65 (m, 2 H), 3.98 (s, 3 H),
4.07 (s, 3 H), 4.27 (q, J = 7.1 Hz, 2 H), 6.21 (d, J = 15.5 Hz, 1 H),
7.32 (s, 1 H), 7.41 (s, 1 H), 8.18 (d, J = 15.5 Hz, 1 H) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 14.1 (CH3), 14.3 (CH3), 22.6 (CH2),
27.6 (CH2), 29.0 (CH2), 29.4 (CH2), 31.7 (CH2), 56.4 (2 CH3), 60.7
(CH2), 105.5 (CH), 106.0 (CH), 119.0 (C), 120.4 (CH), 121.6 (C),
131.9 (C), 139.0 (CH), 148.2 (C), 151.5 (C), 154.9 (C), 166.2 (C),
167.0 (C) ppm. IR (film): ν = 1770 (s), 1703 (s), 1602 (m) cm–1.
˜
MS (CI): m/z (%) = 389 (98) [M + H]+, 388 (100), 387 (13), 343
(65), 342 (30), 272 (16). HRMS (CI): calcd. for C22H29O6 [M +
H]+ 389.1964; found 389.1956.
Ethyl (E)-4-[(Z)-3-Oxoisobenzofuran-1(3H)-ylidene]-4-phenylbut-2-
enoate (8b): The hydrolysis procedure described above for the syn-
thesis of 8a was followed, starting from 4i (35.0 mg, 0.0885 mmol),
and running the reaction for 1 h. The crude mixture was purified
by flash chromatography (silica gel, hexanes/EtOAc, 85:15 to
80:20), to give 8b (23.0 mg, 81%) as a yellow solid, m.p. 145–
147 °C. 1H NMR (300 MHz, CDCl3): δ = 1.31 (t, J = 7.1 Hz, 3 H),
4.25 (q, J = 7.1 Hz, 2 H), 5.89 (d, J = 15.3 Hz, 1 H), 7.32–7.34 (m,
2 H), 7.37–7.48 (m, 3 H), 7.65 (t, J = 7.5 Hz, 1 H), 7.84 (t, J =
7.8 Hz, 1 H), 7.99 (d, J = 7.6 Hz, 1 H), 8.17 (d, J = 8.1 Hz, 1 H),
8.44 (d, J = 15.3 Hz, 1 H) ppm. 13C NMR (75.5 MHz, [D6]acet-
one): δ = 14.5 (CH3), 61.1 (CH2), 123.3 (C), 125.3 (CH), 125.6
(CH), 126.8 (CH), 129.2 (CH), 129.3 (2 CH), 130.9 (2 CH), 132.1
(CH), 135.5 (C), 136.3 (CH), 138.2 (C), 140.2 (CH), 148.4 (C),
[13] a) L. Li, M. Wang, X. J. Zhang, Y. W. Jiang, D. W. Ma, Org.
Lett. 2009, 11, 1309–1312; b) M. Hellal, G. D. Cuny, Tetrahe-
dron Lett. 2011, 52, 5508–5511.
[14] C. Kanazawa, M. Terada, Chem. Asian J. 2009, 4, 1668–1672.
[15] X. Liu, X. Xin, D. X. Xiang, Y. J. Liang, X. Q. Xin, W. L. Li,
D. W. Dong, RSC Adv. 2013, 3, 1346–1349.
[16] F. Bellina, D. Ciucci, P. Vergamini, R. Rossi, Tetrahedron 2000,
56, 2533–2545.
[17] A. Duchene, J. Thibonnet, J. L. Parrain, E. Anselmi, M. Abar-
bri, Synthesis 2007, 597–607.
[18] The corresponding six-membered lactones, analogous to 8, are
available by hydrolysis of the 6-endo-cyclization products 5,[10]
and have also been prepared by oxycyclization/oxidative Heck
cascades from 2-alkynylbenzoate esters: P. Zhao, D. Chen, G.
Song, K. Han, X. Li, J. Org. Chem. 2012, 77, 1579–1584.
6270
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 6263–6271

Regioselective 5-exo-O-Cyclization/Oxidative Heck Cascades
[19] S. Mehta, J. P. Waldo, B. Neuenswander, G. H. Lushington,
R. C. Larock, ACS Comb. Sci. 2013, 15, 247–254.
[20] The interaction of a base with a sulfonamide N–H has been
calculated to have an effect on the regioselectivity of Cu-cata-
lyzed N-nucleophile additions to alkynes: N. T. Patil, A. Nija-
mudheen, A. Datta, J. Org. Chem. 2012, 77, 6179–6185.
[21] a) S. Y. Tang, Q. X. Guo, Y. Fu, Chem. Eur. J. 2011, 17, 13866–
13876; b) B. Li, Y. Park, S. Chang, J. Am. Chem. Soc. 2014,
136, 1125–1131; c) D. Fujino, H. Yorimitsu, A. Osuka, J. Am.
Chem. Soc. 2014, 136, 6255–6258, and references cited therein.
[22]
[23]
CCDC-994241 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.
H. Sashida, A. Kawamukai, Synthesis 1999, 1145–1148.
[24] 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.
Received: June 6, 2014
Published Online: August 15, 2014
Eur. J. Org. Chem. 2014, 6263–6271
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6271