Microwave-assisted domino benzannulation of α-Oxo Ketenes: Preparation of 1,3-Dihydro-2H-1,5-benzodiazepin-2-ones

Article abstract of DOI:10.1002/ejoc.201200093

The microwave irradiation of a series of 2-diazo-1,3-diketones in the presence of an o-phenylenediamine derivative triggered a domino Wolff rearrangement/nucleophilic addition/intramolecular imination sequence to provide a new synthetic entry to 1,3-dihydr-2H-1,5-benzodiazepin-2-ones, a class of molecules with important biological properties. The microwave-assisted reactions of 2-diazo-1,3-diones and o-phenylenediamines in the absence of additives furnished bi-and tricyclic 1,3-dihydro-2H-1,5-benzodiazepin-2-ones by a domino Wolff rearrangement/nucleophilic addition/intramolecular imination sequence with the formation of three new covalent bonds. This reaction is a new and complementary synthetic approach to a class of "drug-like" compounds.

Full text of DOI:10.1002/ejoc.201200093

FULL PAPER
DOI: 10.1002/ejoc.201200093
Microwave-Assisted Domino Benzannulation of α-Oxo Ketenes: Preparation of
1,3-Dihydro-2H-1,5-benzodiazepin-2-ones
Juan-Carlos Castillo,[a] Marc Presset,[b] Rodrigo Abonia,[a] Yoann Coquerel,*[b] and
Jean Rodriguez*[b]
Keywords: Annulation / Diazo compounds / Microwave chemistry / Nitrogen heterocycles / Domino reactions
The microwave irradiation of a series of 2-diazo-1,3-diket-
ones in the presence of an o-phenylenediamine derivative
triggered a domino Wolff rearrangement/nucleophilic ad-
dition/intramolecular imination sequence to provide a new
synthetic entry to 1,3-dihydr-2H-1,5-benzodiazepin-2-ones, a
class of molecules with important biological properties.
Introduction
An important focus of contemporary organic synthesis
is economy (atom, step, redox, pot economies),[1] and, logi-
cally, multiple bond-forming transformations (consecutive,
domino, cascade, “one-pot” reactions)[2] have been devel-
oped that allow the creation of molecular complexity and
functional diversity in a single chemical operation. These
transformations are best performed with polyfunctionalized
substrates in which the distinct reactive groups react selec-
tively in a well-defined order to give a single product.
Densely functionalized molecules such as 1,3-dicarbonyl
compounds are particularly attractive for such endeavors[3]
and α-oxo ketenes[4] exhibiting two carbonyl groups and
one double bond distributed over three carbon atoms fall
into this class of compounds. With very few exceptions, α-
oxo ketenes are highly reactive molecules, and thus their
use in synthesis generally involves their preparation in situ
followed by direct trapping with species present in the reac-
tion mixture. The most commonly used method to generate
α-oxo ketenes involves the thermal decomposition of 1,3-
Scheme 1. Most commonly used methods to generate α-oxo ket-
enes.
We have recently demonstrated that the microwave-as-
sisted Wolff rearrangement of 2-diazoalkane-1,3-diones
produces quantitatively the corresponding α-oxo ketenes
and that this method could advantageously be applied to
domino and/or multicomponent reactions.[6] In this article
we report our studies on the domino reactions of 2-diazo-
alkane-1,3-diones and bis(N-nucleophiles) under microwave
irradiation, and our findings that 2-aminoanilines can lead
efficiently to bi- and tricyclic 1,3-dihydro-2H-1,5-benzodi-
azepin-2-ones under these conditions.
dioxin-4-ones by
a
retro-oxa-Diels–Alder reaction
Results and Discussion
(Scheme 1, left).[4] Alternatively, α-oxo ketenes can also be
obtained by thermal or photochemical Wolff rearrange-
ment[5] of 2-diazo-1,3-dicarbonyl compounds (Scheme 1,
right).
In a previous study we showed that the microwave-as-
sisted Wolff rearrangement is particularly attractive for the
clean synthesis of a variety of β-oxo esters and amides.[6a]
For example, the microwave irradiation of a 1:1 mixture of
the diazo compound 1a and benzylamine in toluene pro-
duced the β-oxo amide 2 in 99% yield and Ͼ95% purity
without need for purification after removal of the volatiles
(Scheme 2). When the same reaction was performed with
2 equiv. of benzylamine, the corresponding β-enamino
amide 3 was obtained in the same yield and purity
[a] Departamento de Química, Universidad del Valle,
A. A. 25360, Cali, Colombia
[b] Aix-Marseille Université – CNRS, Institut des Sciences
Moléculaires de Marseille – iSm2,
Centre Saint Jérôme, Service 531, 13397 Marseille cedex 20,
France
Fax: +33-4-91289187
E-mail: yoann.coquerel@univ-amu.fr
by
a very efficient pseudo-three-component reaction
jean.rodriguez@univ-amu.fr
(Scheme 2).[7] Note that the Wolff rearrangement is the
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200093.
method of choice for the preparation of the α-oxo ketene
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Domino Benzannulation of α-Oxo Ketenes
Scheme 2. Reactions of α-oxo ketenes with primary amines.
in this kind of domino reaction, because it avoids the co- Although these reactions could give rise to the heterocyclic
production of acetone, which may undergo side-reactions products 5 and 7 in a single transformation, they required
with the nucleophilic amines present in the reaction mix- an additive and were poorly efficient when compared with
ture.
The reactivity of α-oxo ketenes has already proven useful
other related domino reactions of α-oxo ketenes.[6]
We then looked for more efficient and valuable bis(N-
for the preparation of a number of heterocycles,[4,6] and the nucleophiles), such as 1,2-anilines, targeting diazepine scaf-
previous observation triggered our interest in the reactions folds. These heterocyclic skeletons, and more particularly
of 2-diazoalkane-1,3-diones with bis(N-nucleophiles) under 1,5-benzodiazepin-2-ones, are an important class of com-
microwave irradiation. Our study was initiated by the reac- pounds with a variety of biological activities, including
tions of the diazo compound 1a with phenylhydrazine and anxiolytic, enzyme-inhibiting, and anti-arrhythmic proper-
urea (Scheme 3). In parallel with the earlier results of Capu- ties (Figure 1).[9] They are considered as “privileged” scaf-
ano et al.,[8] the microwave-assisted Wolff rearrangement of folds in medicinal chemistry and drug development.
1a in the presence of phenylhydrazine afforded the corre-
From the results of our early studies, it was anticipated
sponding acylhydrazine 4, and no heterocycle formation that the 1,3-dihydro-2H-1,5-benzodiazepin-2-one 9a could
was observed. However, when performed in the presence be obtained from o-phenylenediamine (8a) and the α-oxo
of a Lewis acid additive, the same reaction evolved by the ketene 10 derived from the diazo compound 1a. In practice,
cyclization of the intermediate acylhydrazine 4 to give the microwave irradiation of a 1:1 mixture of 1a and 8a af-
bicyclic pyrazole 5 in low to moderate yields depending on forded the desired 1,3-dihydro-2H-1,5-benzodiazepin-2-one
the Lewis acid used. The situation was found to be similar 9a in good yield by a domino reaction without the need for
for the reaction between the diazo compound 1a and urea, additives (Scheme 4). To optimize the time, the reaction was
which required 10 mol-% of BF3·OEt2 to proceed, giving best performed in a sealed reaction vessel under irradiation
the pyrimidinedione 7 via 6, albeit in low yield (Scheme 3). at the maximum power allowed by the dedicated mono-
Scheme 3. Lewis acid catalyzed domino Wolff rearrangement/heterocyclization of 1a with phenylhydrazine and urea.
Eur. J. Org. Chem. 2012, 2338–2345
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J.-C. Castillo, M. Presset, R. Abonia, Y. Coquerel, J. Rodriguez
FULL PAPER
Table 1. Domino benzannulation of α-oxo ketenes.
Figure 1. Representative clinically used 1,5-benzodiazepin-2-ones.
mode microwave reactor used (see the Exp. Sect.) until the
internal pressure reached 17 bar, or the temperature
reached 180 °C, or the total irradiation time reached 6 min.
Scheme 4. Domino reaction of α-oxo ketene 10 with diamine 8a.
Previous work has established that thermally promoted
Wolff rearrangements of cyclic 2-diazoalkane-1,3-diones
such as 1a, which exhibit a blocked s-Z conformation, are
essentially concerted processes that do not involve the for-
mation of a transient α,αЈ-dicarbonyl carbene.[5,10] Also, we
have verified by monitoring the reaction by LC–MS and
NMR spectroscopy that the formation of the β-oxo amide
11 precedes the benzannulation in the domino process.
Based on these considerations, the mechanism for the for-
mation of 9a from 1a and 8a under microwave irradiation
is believed to involve a concerted Wolff rearrangement of
the diazo compound 1a to give the α-oxo ketene 10, fol-
lowed by nucleophilic trapping of the ketene to give the
intermediate β-oxo amide 11, which then undergoes an im-
ination-based benzannulation to give the product 9a
(Scheme 4).
Most of the previous approaches to benzodiazepines of
type 9 involve the condensation of o-phenylenediamines
and β-oxo esters (or synthetic equivalents) via enamino es-
ter intermediates. These reactions were found to be ex-
tremely substrate- and conditions-dependent, usually re-
quiring relatively long reaction times (typically hours), and
are often complicated by competitive reactions leading to
N-alkenylbenzimidazol-2-one and/or benzimidazole deriva-
tives.[11] A remarkable feature of this method is that it does
not involve an enamino ester intermediate, the formation of
the amide bond preceding the formation of the imine bond
[a] Unless otherwise specified (Entries 3, 5, 7, 11, and 13), all reac-
tions were performed in sealed reaction vessels under irradiation at
the maximum power allowed by the dedicated monomode micro-
wave reactor used (see the Exp. Sect.) until the internal pressure
reached 17 bar, or the temperature reached 180 °C, or the total irra-
diation time reached 6 min. [b] Yields of the isolated pure com-
pounds were obtained after silica gel flash chromatography.
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Domino Benzannulation of α-Oxo Ketenes
Scheme 5. Benzannulation reaction with the acyclic diazo compound 1f.
in the product 9a. This alternative approach should be more benzodiazepinones 9d,h,i, to convert easily into the corre-
general, faster, and some side-reactions should be sup- sponding N-alkenylbenzimidazol-2-ones 12d,h,i are not
pressed. Thus, the scope and limits of this new domino clearly understood.
benzannulation reaction of α-oxo ketenes were studied, and
In the case of the acyclic diazo compound 1f, the reac-
the results are reported in Table 1. With the six- and five- tions with 8a–c led to the formation of the desired 1,3-dihy-
membered cyclic diazo precursors 1b and 1c, the corre- dro-2H-1,5-benzodiazepin-2-ones 9j–l, but, interestingly,
sponding ring-contracted 1,3-dihydro-2H-1,5-benzodiaz- these products were always accompanied by minor amounts
epin-2-ones 9b and 9c were obtained in good and low of the corresponding 2-acetyl-3-methylquinoxalines 16a–c
yields, respectively (Entries 2 and 3). With the seven-mem- (Scheme 5). The most striking feature of the side-reactions
bered diazo precursor 1d, the reaction unexpectedly af- leading to 16a–c[13] is that no Wolff rearrangement occurred
forded the N-cyclohexenylbenzimidazol-2-one 12d in good in these transformations. We believe that this is due to the
yield as the only isolable product (Entry 4). The formation unblocked conformation of the acyclic diazo compound 1f,
of N-alkenylbenzimidazol-2-one byproducts of type 12 has which probably decomposes thermally to give at least a
previously been observed in reactions of o-phenylenedi- fraction of the corresponding α,αЈ-dicarbonyl carbene. In
amines with β-oxo esters,[11] and it has been demonstrated the presence of o-phenylenediamines 8a–c, this carbene
that the benzimidazolones of type 12 are actually obtained would undergo an insertion reaction into one N–H bond to
by a thermal rearrangement of the benzodiazepinones 9.[12] give the corresponding 2-amino 1,3-diketones, which would
Accordingly, the formation of 12d could essentially be avo- then undergo heterocyclization (intramolecular imination)
ided when the reaction between 1d and 8a was performed followed by an aromatizative dehydrogenation step to give
at 130 °C for 2 min, leading efficiently to the 1,3-dihydro- the products 16a–c.
2H-1,5-benzodiazepin-2-one 9d (Entry 5). In the case of the
eight-membered cyclic diazo precursor 1e, both the ex-
pected 1,3-dihydro-2H-1,5-benzodiazepin-2-one 9e and the
N-cycloheptenylbenzimidazol-2-one 12e were obtained in a
Conclusions
3:1 ratio under the standard reaction conditions (Entry 6),
The pseudo-three-component reaction of 2-diazodime-
whereas only 9e was obtained at lower temperature (En- done (1a) with benzylamine leading to the corresponding
try 7). Similar trends were observed in the reactions with enamino amide 3 has been exploited for the selective one-
4,5-dichloro- and 4,5-dimethylbenzene-1,2-diamine (8b and pot construction of various heterocyclic scaffolds of syn-
8c, respectively) as the bis(N-nucleophile). With 8b, the six- thetic and biologic importance when bis(N-nucleophiles)
membered diazo compound 1a gave the corresponding 1,3- are involved as partners. The microwave-assisted reaction
dihydro-2H-1,5-benzodiazepin-2-one 9f as a 1:2 mixture of with phenylhydrazine or urea required the presence of a
its imine and enamine forms (Entry 8), whereas with 8c, the catalytic amount of BF3·OEt to give the pyrazole 5 or the
benzodiazepinone product 9g was found somewhat un- pyrimidinedione 7, respectively, according to a domino
stable, and thus the crude product was directly reduced by Wolff rearrangement/nucleophilic addition/intramolecular
treatment with sodium cyanoborohydride to give the corre- imination sequence. Although not very productive, these re-
sponding 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-ones actions are interesting examples of domino reactions of α-
13g and 14g in 69% combined yield (dr 13g/14g = 2.7:1, oxo ketenes performed in the presence of a Lewis acid. Im-
Entry 9). Finally, with both diamines 8b and 8c, the sharply portantly, the microwave-assisted reactions between the 2-
divergent reactivity of the seven-membered diazo com- diazo-1,3-diones 1 and the o-phenylenediamines 8 in the ab-
pound 1d afforded the N-cyclohexenylbenzimidazol-2-ones sence of any additive furnished a series of bi- and tricyclic
12h and 12i, respectively (Entries 10 and 12). As before, the 1,3-dihydro-2H-1,5-benzodiazepin-2-ones 9 according to
reactions performed at lower temperature led to the desired another domino Wolff rearrangement/nucleophilic ad-
benzodiazepinones 9h (as a 1:5 mixture of regioisomers, En- dition/intramolecular imination sequence. This reaction has
try 11) and 9i (Entry 13). The reasons for the propensity of led to a number of interesting observations and represents
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J.-C. Castillo, M. Presset, R. Abonia, Y. Coquerel, J. Rodriguez
solid. Rf (40% EtOAc/petroleum ether)
0.69. 1H NMR
(300 MHz, CDCl3): δ = 7.41–7.39 (m, 5 H), 7.19–7.14 (m, 1 H),
2.77 (s, 2 H), 2.48 (s, 2 H), 1.27 (s, 6 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 158.4 (C), 149.2 (C), 139.6 (C), 129.4 (CH), 129.4
(CH), 124.8 (CH), 118.6 (CH), 118.6 (CH), 111.5 (C), 47.5 (C),
42.5 (CH2), 37.8 (CH2), 30.1 (CH3), 30.1 (CH3) ppm. MS (ESI+):
m/z = 251 [M + Na]+, 267 [M + K]+.
FULL PAPER
=
a new and advantageously complementary synthetic ap-
proach to a valuable class of “drug-like” compounds.
Experimental Section
General: Reactions under microwave irradiation were performed in
oven-dried 10 mL sealable Pyrex tubes equipped with a Teflon-
coated stirring bar (obtained from CEM). All reactions under mi-
crowave irradiation (ν = 2.45 GHz) were performed in a CEM Dis-
cover 1-300W system equipped with a built-in pressure measure-
ment sensor and a vertically focused IR temperature sensor. All
reagents were obtained from commercial sources and used as sup-
plied unless otherwise stated. Anhydrous toluene was obtained
from an MBraun SPS-800 solvent purification system. Petroleum
ether refers to the fraction of petroleum ether distilled between 40
and 65 °C. The reactions were monitored by TLC, which was per-
formed on Merck 60F254 plates and visualized with an ethanolic
solution of p-anisaldehyde and sulfuric acid or an ethanolic solu-
tion of molybdophosphoric acid. Flash chromatography was per-
formed with Merck 230–400 mesh silica gel. NMR spectroscopic
data were recorded with a Bruker Avance 300 spectrometer in
CDCl3, (CD3)2SO, or C6D6. The chemical shifts (δ) are given in
Compound 7:[8] Boron trifluoride–diethyl ether (8 μL, 0.06 mmol)
was added to
a solution of 2-diazodimedone (1a, 98 mg,
0.59 mmol) and urea (35 mg, 0.59 mmol) in anhydrous toluene
(2 mL), and the resulting mixture was subjected to microwave irra-
diation at 300 W for 2.5 min (Tmax = 180 °C), after which the reac-
tion mixture was cooled to 50 °C with an air flow. After removal of
the volatiles under vacuum, the resulting crude product was directly
purified by flash chromatography eluting with EtOAc/petroleum
ether to afford pure 7 (28 mg, 26%) as a yellow oil. Rf (30% EtOAc/
petroleum ether) = 0.26. 1H NMR (300 MHz, CDCl3): δ = 8.84
(br. s, 1 H), 2.59 (dd, J = 1.8, 1.8 Hz, 2 H), 2.47 (dd, J = 1.8,
1.8 Hz, 2 H), 1.74 (br. s, 1 H), 1.21 (s, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 167.6 (C), 160.5 (C), 148.8 (C), 111.0 (C),
45.6 (CH2), 39.9 (CH2), 36.7 (C), 29.7 (CH3), 29.7 (CH3) ppm. MS
(ESI+): m/z = 203 [M + Na]+, 219 [M + K]+.
1
General Procedure for the Synthesis of Compounds 9, 12–14, and/or
16: A solution of 2-diazo 1,3-diketone 1 and o-phenylenediamine 8
(1.0 equiv.) in anhydrous toluene (ca. 2 mL) was subjected to micro-
wave irradiation at 300 W until the temperature reached 180 °C, or
the pressure reached 17 bar, or for a maximum time of 6 min, after
which the reaction mixture was cooled to 50 °C with an air flow.
After removal of the volatiles under vacuum, the resulting crude
product was directly purified by flash chromatography eluting with
EtOAc/petroleum ether to afford pure 9, 12 and/or 16.
ppm relative to the residual non-deuteriated solvent signal for H
NMR [CHCl3: δ = 7.26 ppm; (CH3)2SO: δ = 2.50 ppm; C6D6: δ =
7.15 ppm] and relative to the deuteriated solvent signal for 13C
NMR [CDCl3: δ = 77.0 ppm; (CD3)2SO: δ = 39.4 ppm; C6D6: δ =
128.02 ppm]; coupling constants (J) are given in Hz. The classical
abbreviations are used to describe signal multiplicity. Mass spectra
were recorded with a Bruker Esquire 6000 spectrometer equipped
with an electrospray ionization source and an ion-trap detector.
Melting points were measured with a Büchi B-540 apparatus.
HRMS data were obtained from Spectropole (http://www.
spectropole.u-3mrs.fr/). Diazo compounds 1a–f were prepared from
the corresponding 1,3-diketones by diazo transfer reactions with
TsN3 according to the procedures described in ref.[14] Compound 2
was prepared as described previously.[6a]
Compound 9a: According to the general procedure (6 min), the re-
action between 1a (50 mg, 0.30 mmol) and 8a (33 mg, 0.30 mmol)
afforded compound 9a as an orange oil (52 mg, 76%). Rf (30%
EtOAc/petroleum ether) = 0.41. 1H NMR (300 MHz, C6D6): δ =
9.76 (br. s, 1 H), 7.58–7.54 (m, 1 H), 7.02–6.99 (m, 1 H), 6.92–6.89
(m, 2 H), 2.71 (dd, J = 7.0, 13.3 Hz, 1 H), 2.42 (dd, J = 7.0, 9.0 Hz,
1 H), 2.37–2.21 (m, 2 H), 1.43 (dd, J = 9.0, 13.3 Hz, 1 H), 0.94 (s,
3 H), 0.74 (s, 3 H) ppm. 13C NMR (75 MHz, C6D6): δ = 174.9 (C),
169.5 (C), 140.8 (C), 130.0 (C), 128.7 (CH), 126.2 (CH), 124.7
(CH), 122.6 (CH), 50.2 (CH2), 48.7 (CH), 38.7 (CH2), 36.7 (C),
28.3 (CH3), 28.1 (CH3) ppm. MS (ESI+): m/z = 251 [M + Na]+.
HRMS (ESI+): calcd. for [C14H17N2O]+ [M + H]+ 229.1335; found
229.1332.
Compound 3:
A solution of 2-diazodimedone (1a; 250 mg,
1.50 mmol) and benzylamine (329 μL, 3.00 mmol) in anhydrous
toluene (2 mL) was subjected to microwave irradiation at 300 W
for 3.5 min (Tmax = 180 °C), after which the reaction mixture was
cooled to 50 °C with an air flow. Concentration of the reaction
mixture followed by high-vacuum removal of the volatiles afforded
the clean crude product 3 as a colorless oil (499 mg, 99%) without
1
need for purification. Rf (20% EtOAc/petroleum ether) = 0.59. H
NMR (300 MHz, CDCl3): δ = 8.34 (br. s, 1 H), 7.34–7.26 (m, 10
H), 5.18 (br. s, 1 H), 4.49 (d, J = 6.3 Hz, 2 H), 4.34 (d, J = 6.3 Hz,
2 H), 2.36 (s, 2 H), 2.27 (s, 2 H), 1.11 (s, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 168.8 (C), 160.3 (C), 139.7 (C), 139.4 (C),
128.5 (CH), 128.5 (CH), 128.5 (CH), 128.5 (CH), 127.6 (CH), 127.6
(CH), 127.0 (CH), 126.9 (CH), 126.6 (CH), 126.6 (CH), 93.2 (C),
48.0 (CH2), 46.2 (CH2), 44.3 (CH2), 42.8 (CH2), 35.7 (C), 29.7
(CH3), 29.7 (CH3) ppm. MS (ESI+): m/z = 335 [M + H]+, 357 [M
+ Na]+, 373 [M + K]+.
Compound 9b: According to the general procedure (1.5 min), the
reaction between 1b (102 mg, 0.74 mmol) and 8a (80 mg,
0.74 mmol) afforded compound 9b as an orange oil (82 mg, 55%).
Rf (30% EtOAc/petroleum ether) = 0.15. 1H NMR (300 MHz,
CDCl3): δ = 9.28 (br. s, 1 H), 7.36–7.33 (m, 1 H), 7.19–7.16 (m, 2
H), 7.08–7.05 (m, 1 H), 2.87–2.64 (m, 4 H), 2.02–1.95 (m, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 176.3 (C), 168.4 (C), 140.6
(C), 128.7 (C), 127.4 (CH), 126.1 (CH), 124.7 (CH), 122.3 (CH),
48.7 (CH), 35.7 (CH2), 25.3 (CH2), 23.5 (CH2) ppm. MS (ESI+):
m/z = 201 [M + H]+, 223 [M + Na]+, 239 [M + K]+, 423 [2 M +
Na]+. HRMS (ESI+): calcd. for [C12H13N2O]+ [M + H]+ 201.1022;
found 201.1223.
Compound 5:[8] Boron trifluoride–diethyl ether (7 μL, 0.05 mmol)
was added to
a solution of 2-diazodimedone (1a; 78 mg,
0.47 mmol) and phenylhydrazine (49 μL, 0.47 mmol) in anhydrous
toluene (2 mL), and the resulting mixture was subjected to micro-
Compound 9c: A solution of 2-diazocyclopentane-1,3-dione (1c;
wave irradiation at 300 W for 2.6 min (Tmax = 180 °C), after which 66 mg, 0.53 mmol) and o-phenylenediamine (8a; 58 mg, 0.53 mmol)
the reaction mixture was cooled to 50 °C with an air flow. After
removal of the volatiles under vacuum, the resulting crude product
was directly purified by flash chromatography eluting with EtOAc/
in anhydrous toluene (2 mL) was subjected to microwave irradia-
tion at 180 °C for 5 min (ramp up time: 4 min), after which the
reaction mixture was cooled to 50 °C with an air flow. After re-
petroleum ether to afford pure 5 (46 mg, 42%) as a red-orange moval of the volatiles under vacuum, the resulting crude product
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Domino Benzannulation of α-Oxo Ketenes
was directly purified by flash chromatography eluting with EtOAc/
H), 7.24–7.15 (m, 2 H), 7.08–7.03 (m, 1 H), 2.76–2.68 (m, 2 H),
petroleum ether to afford pure 9c as a pink solid (23 mg, 23%). Rf 2.54–2.46 (m, 1 H), 2.29–1.84 (m, 5 H), 1.64–1.43 (m, 2 H), 1.19–
(50% EtOAc/petroleum ether) = 0.25. 1H NMR (300 MHz, 1.08 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 171.1 (C),
CDCl3): δ = 8.67 (br. s, 1 H), 7.38–7.35 (m, 1 H), 7.21–7.17 (m, 2 168.9 (C), 139.4 (C), 128.9 (C), 127.1 (CH), 125.8 (CH), 124.7
H), 7.07–7.03 (m, 1 H), 3.74 (dd, J = 4.9, 8.8 Hz, 1 H), 3.27–3.21
(m, 2 H), 2.75–2.63 (m, 1 H), 2.47–2.34 (m, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 171.6 (C), 169.2 (C), 139.2 (C), 128.5 (C),
(CH), 121.4 (CH), 50.7 (CH), 38.2 (CH2), 30.5 (CH2), 28.4 (CH2),
26.6 (CH2), 25.4 (CH2) ppm. MS (ESI+): m/z = 229 [M + H]+, 251
[M + Na]+. HRMS (ESI+): calcd. for [C14H17N2O]+ [M + H]+
128.0 (CH), 126.6 (CH), 125.0 (CH), 122.8 (CH), 53.3 (CH), 35.8 229.1335; found 229.1337.
(CH2), 15.2 (CH2) ppm. MS (ESI+): m/z = 209 [M + Na]+. HRMS
Compound 9f: According to the general procedure (3 min), the reac-
(ESI+): calcd. for [C11H11N2O]+ [M + H]+ 187.2173; found
187.2169.
tion between 1a (84 mg, 0.51 mmol) and 8b (90 mg, 0.50 mmol)
afforded compound 9f (74 mg, 49%) as a yellow solid containing
the two regioisomeric forms in a 1:2 ratio. 9f (Imine Form): Rf (40%
EtOAc/petroleum ether) = 0.45. 1H NMR (300 MHz, [D6]DMSO):
δ = 10.55 (s, 1 H), 7.51 (s, 1 H), 7.35 (s, 1 H), 3.19 (dd, J = 6.9,
8.8 Hz, 1 H), 2.41 (dd, J = 6.9, 8.8 Hz, 1 H), 2.37 (s, 2 H), 1.75
(dd, J = 8.8, 13.2 Hz, 1 H), 1.12 (s), 0.99 (s) ppm. MS (ESI+): m/z
= 321/319 [M + Na]+. 9f (Enamine Form): Rf (40% EtOAc/petro-
leum ether) = 0.45. M.p. 230–231 °C. 1H NMR (300 MHz, [D6]-
DMSO): δ = 8.52 (s, 1 H), 8.33 (s, 1 H), 6.91 (s, 1 H), 6.79 (s, 1 H),
2.23 (s, 4 H), 1.03 (s, 6 H) ppm. 13C NMR (75 MHz/[D6]DMSO): δ
= 166.5 (C), 153.1 (C), 134.6 (C), 130.1 (C), 123.9 (C), 123.9 (C),
120.9 (CH), 119.5 (CH), 101.5 (C), 49.6 (CH2), 45.7 (CH2), 34.1
(C), 28.9 (CH3), 28.9 (CH3) ppm. MS (ESI+): m/z = 321/319 [M +
Na]+.
Compound 12d:[15] According to the general procedure (3 min), the
reaction between 1d (263 mg, 1.73 mmol) and 8a (194 mg,
1.80 mmol) afforded compound 12d as a white solid (222 mg,
59%). Rf (80% EtOAc/petroleum ether) = 0.18. M.p. 183–184 °C.
1H NMR (300 MHz, CDCl3): δ = 10.86 (m, 1 H), 7.15–7.11 (m, 1
H), 7.07–6.97 (m, 3 H), 6.00–5.97 (m, 1 H), 2.41–2.38 (m, 2 H),
2.33–2.28 (m, 2 H), 1.92–1.84 (m, 2 H), 1.79–1.74 (m, 2 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 154.9 (C), 132.0 (C), 130.6 (C),
128.5 (C), 127.6 (CH), 121.5 (CH), 121.0 (CH), 109.8 (CH), 108.6
(CH), 26.7 (CH2), 24.7 (CH2), 22.5 (CH2), 21.6 (CH2) ppm. MS
(ESI+): m/z = 237 [M + Na]+, 253 [M + K]+, 451 [2 M + Na]+.
Compound 9d:[11c,11f] A solution of 2-diazocycloheptane-1,3-dione
(1d; 102 mg, 0.67 mmol) and o-phenylenediamine (8a; 77 mg,
0.71 mmol) in anhydrous toluene (2 mL) was subjected to micro-
wave irradiation at 130 °C for 2 min (ramp up time: 2 min), after
which the reaction mixture was cooled to 50 °C with an air flow.
After removal of the volatiles under vacuum, the resulting crude
product was directly purified by flash chromatography eluting with
EtOAc/petroleum ether to afford compound 9d (88 mg, 62%) as a
pale-yellow solid. Rf (40% EtOAc/petroleum ether) = 0.18. M.p.
Compounds 13g and 14g: According to the general procedure
(3 min), the reaction between 1a (123 mg, 0.74 mmol) and 8c
(98 mg, 0.72 mmol) afforded crude 9g, which was not purified. This
material was dissolved in MeOH (3 mL) and acetic acid (43 μL,
0.75 mmol), and NaBH3CN (47 mg, 0.74 mmol) was added at
room temperature. After 5 h, the reaction mixture was concen-
trated, diluted with EtOAc and water, and the organic layer was
separated. The aqueous phase was extracted once with EtOAc, and
the combined organic layers were washed with brine, dried with
anhydrous Na2SO4, filtered, and concentrated to give the crude
product, which was purified by flash chromatography eluting with
EtOAc/petroleum ether to afford first compound 13g (72 mg, 51%)
as a white solid and then 14g (25 mg, 18%) as a white solid. 13g: Rf
1
180–181 °C. H NMR (300 MHz, [D6]DMSO): δ = 10.37 (s, 1 H),
7.28–7.23 (m, 1 H), 7.18–7.10 (m, 3 H), 2.73–2.62 (m, 2 H), 2.29–
2.12 (m, 2 H), 1.86–1.47 (m, 5 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 167.6 (C), 165.5 (C), 138.5 (C), 129.9 (C), 126.7 (CH),
125.1 (CH), 123.7 (CH), 121.5 (CH), 44.3 (CH), 34.4 (CH2), 22.7
(CH2), 22.5 (CH2), 21.1 (CH2) ppm. MS (ESI+): m/z = 215 [M +
H]+, 237 [M + Na]+.
1
(30% EtOAc/petroleum ether) = 0.18. M.p. 211–212 °C. H NMR
(300 MHz, CDCl3): δ = 7.59 (s, 1 H), 6.53 (s, 1 H), 6.43 (s, 1 H),
3.88 (ddd, J = 9.0, 9.0, 9.0 Hz, 1 H), 3.81 (s, 1 H), 2.95 (ddd, J =
9.0, 9.0, 9.0 Hz, 1 H), 2.18–2.10 (m, 7 H), 2.05 (dd, J = 7.2,
12.4 Hz, 1 H), 1.76 (dd, J = 9.0, 13.6 Hz, 1 H), 1.45 (dd, J = 9.0,
12.1 Hz, 1 H), 1.10 (s, 3 H), 1.09 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 174.0 (C), 135.0 (C), 133.5 (C), 126.8 (C), 123.7 (CH),
120.6 (C), 119.8 (CH), 59.6 (CH), 50.3 (CH), 50.1 (CH2), 39.9
(CH2), 37.1 (C), 30.8 (CH3), 30.4 (CH3), 18.9 (CH3), 18.3 (CH3)
ppm. MS (ESI+): m/z = 259 [M + H]+, 281 [M + Na]+, 297 [M +
K]+. HRMS (ESI+): calcd. for [C16H23N2O]+ [M + H]+ 259.1805;
found 259.1806. 14g: Rf (30% EtOAc/petroleum ether) = 0.15. M.p.
Compounds 9e and 12e: According to the general procedure (4 min),
the reaction between 1e (39 mg, 0.24 mmol) and 8a (27 mg,
0.25 mmol) afforded an inseparable mixture of compounds 12e and
9e (43 mg, 80%, 12e/9e = 19:61). 12e: Rf (50% EtOAc/petroleum
1
ether) = 0.11. H NMR (300 MHz, CDCl3, selected resonances): δ
= 9.96 (s, 1 H), 6.07 (dd, J = 6.3, 6.3 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl3, selected resonances): δ = 131.7 (CH), 121.0
(CH), 109.4 (CH), 108.7 (CH), 32.6 (CH2), 31.4 (CH2), 27.0 (CH2),
26.7 (CH2), 26.1 (CH2) ppm. 9e: Rf (50% EtOAc/petroleum ether)
1
= 0.11. H NMR (300 MHz, CDCl3, selected resonance): δ = 9.14
(s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 171.0 (C), 168.9
(C), 139.4 (C), 129.0 (C), 127.1 (CH), 125.8 (CH), 124.7 (CH),
121.5 (CH), 50.7 (CH), 38.1 (CH2), 30.5 (CH2), 28.4 (CH2), 26.6
(CH2), 25.4 (CH2) ppm.
1
224–225 °C. H NMR (300 MHz, CDCl3): δ = 7.61 (s, 1 H), 6.71
(s, 1 H), 6.69 (s, 1 H), 4.10 (ddd, J = 6.3, 9.0, 9.0 Hz, 1 H), 3.25
(br. s, 1 H), 3.01 (ddd, J = 6.3, 9.0, 9.0 Hz, 1 H), 2.32 (dd, J = 6.3,
13.2 Hz, 1 H), 2.18 (s, 6 H), 1.79–1.53 (m, 3 H), 1.16 (s, 3 H), 0.98
(s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 175.0 (C), 138.7
(C), 133.6 (C), 131.6 (C), 128.7 (C), 123.0 (CH), 122.8 (CH), 66.7
(CH), 48.1 (CH2), 46.9 (CH), 40.8 (CH2), 36.6 (C), 30.1 (CH3),
30.1 (CH3), 19.0 (CH3), 18.9 (CH3) ppm. MS (ESI+): m/z = 259
[M + H]+, 281 [M + Na]+, 297 [M + K]+. HRMS (ESI+): calcd.
for [C16H23N2O]+ [M + H]+ 259.1805; found 259.1802.
Compound 9e: A solution of 2-diazocyclooctane-1,3-dione (1e;
85 mg, 0.51 mmol) and o-phenylenediamine (8a; 56 mg, 0.52 mmol)
in anhydrous toluene (2 mL) was subjected to microwave irradia-
tion at 130 °C for 2 min (ramp up time: 2 min), after which the
reaction mixture was cooled to 50 °C with an air flow. After re-
moval of the volatiles under vacuum, the resulting crude product
was directly purified by flash chromatography eluting with EtOAc/
petroleum ether to afford compound 9e (65 mg, 57%) as a yellow Compound 12h: According to the general procedure (5 min), the
solid. Rf (50% EtOAc/petroleum ether) = 0.11. M.p. 180–181 °C.
reaction between 1d (95 mg, 0.62 mmol) and 8b (111 mg,
0.62 mmol) afforded compound 12h as a pink solid (124 mg, 70%).
1H NMR (300 MHz, CDCl3): δ = 8.83 (s, 1 H), 7.38–7.34 (m, 1
Eur. J. Org. Chem. 2012, 2338–2345
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2343

J.-C. Castillo, M. Presset, R. Abonia, Y. Coquerel, J. Rodriguez
FULL PAPER
Rf (50% EtOAc/petroleum ether) = 0.22. M.p. 256–257 °C. 1H
NMR (300 MHz, [D6]DMSO): δ = 11.19 (s, 1 H), 7.17 (s, 1 H),
7.16 (s, 1 H), 5.88–5.86 (m, 1 H), 2.28–2.20 (m, 4 H), 1.77–1.61 (m,
4 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 152.7 (C), 131.2
(C), 130.1 (C), 128.3 (C), 126.7 (CH), 122.8 (C), 122.6 (C), 110.0
= 1.2, 8.2 Hz, 1 H), 8.04 (dd, J = 1.2, 8.5 Hz, 1 H), 7.83 (ddd, J =
1.5, 7.6, 8.5 Hz, 1 H), 7.75 (ddd, J = 1.5, 7.5, 8.2 Hz, 1 H), 2.96 (s,
3 H), 2.84 (s, 3 H) ppm; NH resonances not detected. 13C NMR
(75 MHz, CDCl3): δ = 201.3 (C), 153.0 (C), 147.1 (C), 142.5 (C),
139.7 (C), 132.0 (CH), 129.8 (CH), 129.5 (CH), 128.3 (CH), 27.7
(CH), 109.3 (CH), 25.9 (CH2), 23.9 (CH2), 21.9 (CH2), 20.9 (CH2) (CH3), 24.3 (CH3) ppm. MS (ESI+): m/z = 189 [M + H]+, 211 [M
ppm. MS (ESI+): m/z = 307/305 [M + Na]+. HRMS (ESI+): calcd.
+ Na]+, 227 [M + K]+. 9j: Rf (40% EtOAc/petroleum ether) = 0.15.
for [C13H13N2OCl2]+ [M + H]+ 283.0399; found 283.0400.
M.p. 167–168 °C. H NMR (300 MHz, CDCl3): δ = 9.16 (br. s, 1
1
H), 7.35–7.32 (m, 1 H), 7.22–7.15 (m, 2 H), 7.10–7.05 (m, 1 H),
2.81 (q, J = 6.9 Hz, 1 H), 2.24 (s, 3 H), 1.47 (d, J = 6.9 Hz, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 168.8 (C), 166.3 (C), 139.1
(C), 128.8 (C), 127.0 (CH), 125.9 (CH), 124.8 (CH), 121.5 (CH),
44.0 (CH), 23.0 (CH3), 10.9 (CH3) ppm. MS (ESI+): m/z = 189 [M
+ H]+, 211 [M + Na]+, 227 [M + K]+. HRMS (ESI+): calcd. for
[C11H13N2O]+ [M + H]+ 189.1022; found 189.1020.
Compound 9h: A solution of 2-diazocycloheptane-1,3-dione (1d;
100 mg, 0.66 mmol) and diamine 8b (116 mg, 0.65 mmol) in anhy-
drous toluene (2 mL) was subjected to microwave irradiation at
130 °C for 2 min (ramp up time: 2 min), after which the reaction
mixture was cooled to 50 °C with an air flow. After removal of the
volatiles under vacuum, the resulting crude product was directly
purified by flash chromatography eluting with EtOAc/petroleum
ether to afford compound 9h (112 mg, 61%) as a yellow solid con-
taining the two regioisomeric forms of 9h in a 1:5 ratio. Rf (50%
EtOAc/petroleum ether) = 0.45. 1H NMR (300 MHz, [D6]DMSO):
δ = 10.5 (s, 1 H, enamine form), 8.95 (s, 1 H, imine form), 7.51 (s,
1 H), 7.46 (s, 1 H), 7.33 (s, 1 H, enamine form), 7.00 (s, 1 H), 6.97
(s, 1 H), 2.79–2.65 (m), 2.30–2.07 (m), 1.85–1.82 (m), 1.71–1.45 (m)
ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 169.5 (C), 168.3 (C),
167.4 (C), 152.3 (C), 138.3 (C), 138.0 (C), 131.0 (C), 130.0 (C),
127.8 (CH), 126.8 (C), 125.3 (C), 124.4 (C), 123.9 (C), 122.5 (CH),
120.6 (CH), 119.9 (CH), 105.2 (C), 44.8 (CH), 34.5 (CH2), 30.4
(CH2), 25.0 (CH2), 22.6 (CH2), 22.3 (CH2), 21.8 (CH2), 21.7 (CH2),
20.9 (CH2) ppm. MS (ESI+): m/z = 307/305 [M + Na]+.
Compounds 9k and 16b: According to the general procedure
(3 min), the reaction between 1f (118 mg, 0.94 mmol) and 8b
(166 mg, 0.93 mmol) afforded first 16b (21 mg, 9%) and then 9k
(106 mg, 44%) as yellow and white solids, respectively. 16b: Rf
1
(30% EtOAc/petroleum ether) = 0.80. M.p. 144–145 °C. H NMR
(300 MHz, CDCl3): δ = 8.24 (s, 1 H), 8.15 (s, 1 H), 2.94 (s, 3 H),
2.80 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 200.6 (C),
154.4 (C), 147.8 (C), 141.3 (C), 138.4 (C), 136.7 (C), 134.3 (C),
130.2 (CH), 129.1 (CH), 27.7 (CH3), 24.4 (CH3) ppm. MS (ESI+):
m/z = 279/277 [M + Na]+. 9k: Rf (30% EtOAc/petroleum ether) =
0.20. M.p. 205–206 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 10.6
(s, 1 H), 7.47 (s, 1 H), 7.33 (s, 1 H), 2.81 (q, J = 6.9 Hz, 1 H), 2.12
(s, 3 H), 1.31 (d, J = 6.9 Hz, 3 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 168.3 (C), 167.2 (C), 138.6 (C), 129.8 (C), 127.5 (CH),
126.9 (C), 125.3 (C), 122.5 (CH), 44.2 (CH), 22.6 (CH3), 10.7 (CH3)
ppm. MS (ESI+): m/z = 259/257 [M + H]+, 281/279 [M + Na]+.
HRMS (ESI+): calcd. for [C11H11Cl2N2O]+ [M + H]+ 257.0243;
found 257.0247.
Compound 12i: According to the general procedure (4 min), the re-
action between 1d (158 mg, 1.04 mmol) and 8c (147 mg,
1.08 mmol) afforded compound 12i as a white solid (156 mg, 62%).
Rf (40% EtOAc/petroleum ether) = 0.15. M.p. 256–257 °C. 1H
NMR (300 MHz, CDCl3): δ = 10.5 (br. s, 1 H), 6.93 (s, 1 H), 6.76
(s, 1 H), 5.97–5.94 (m, 1 H), 2.40–2.38 (m, 2 H), 2.34–2.26 (m, 8
H), 1.92–1.84 (m, 2 H), 1.80–1.74 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 155.0 (C), 132.2 (C), 129.6 (C), 129.1 (C),
128.7 (C), 127.2 (CH), 126.3 (C), 110.9 (CH), 109.5 (CH), 26.7
(CH2), 24.6 (CH2), 22.5 (CH2), 21.6 (CH2), 19.8 (CH3), 19.7 (CH3)
ppm. MS (ESI+): m/z = 265 [M + Na]+, 281 [M + K]+. HRMS
(ESI+): calcd. for [C15H19N2O]+ [M + H]+ 243.1492; found
243.1490.
Compounds 9l and 16c:[13] According to the general procedure
(3 min), the reaction between 1f (160 mg, 1.27 mmol) and 8c
(173 mg, 1.27 mmol) afforded first 16c (34 mg, 12%) and then 9l
(132 mg, 48%) as white solids. 16c: Rf (40% EtOAc/petroleum
1
ether) = 0.59. M.p. 130–131 °C. H NMR (300 MHz, CDCl3): δ =
7.85 (s, 1 H), 7.77 (s, 1 H), 2.93 (s, 3 H), 2.81 (s, 3 H), 2.50 (s, 3
H), 2.49 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 201.5 (C),
152.1 (C), 146.3 (C), 143.0 (C), 141.6 (C), 140.1 (C), 138.7 (C),
128.7 (CH), 127.4 (CH), 27.7 (CH3), 24.3 (CH3), 20.6 (CH3), 20.1
(CH3) ppm. MS (ESI+): m/z = 237 [M + Na]+. 9l: Rf (40% EtOAc/
petroleum ether) = 0.12. M.p. 181–182 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.72 (s, 1 H), 7.10 (s, 1 H), 6.80 (s, 1 H), 2.80 (q, J =
6.9 Hz, 1 H), 2.24 (s, 6 H), 2.22 (s, 3 H), 1.45 (d, J = 6.9 Hz, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 168.5 (C), 165.1 (C), 137.2
(C), 134.8 (C), 133.5 (C), 127.5 (CH), 126.5 (C), 121.9 (CH), 43.9
(CH), 22.9 (CH3), 19.2 (CH3), 19.1 (CH3), 11.0 (CH3) ppm. MS
(ESI+): m/z = 217 [M + H]+, 239 [M + Na]+, 255 [M + K]+. HRMS
Compound 9i: A solution of 2-diazocycloheptane-1,3-dione (1d;
98 mg, 0.65 mmol) and diamine 8c (89 mg, 0.65 mmol) in anhy-
drous toluene (2 mL) was subjected to microwave irradiation at
130 °C for 2 min (ramp up time: 2 min), after which the reaction
mixture was cooled to 50 °C with an air flow. After removal of the
volatiles under vacuum, the resulting crude product was directly
purified by flash chromatography eluting with EtOAc/petroleum
ether to afford compound 9i as a yellow solid (115 mg, 73%). Rf
1
(50% EtOAc/petroleum ether) = 0.25. M.p. 173–174 °C. H NMR
(300 MHz, [D6]DMSO): δ = 10.19 (s, 1 H), 7.03 (s, 1 H), 6.86 (s, 1
H), 2.68–2.59 (m, 2 H), 2.25–2.14 (m, 8 H), 1.85–1.45 (m, 5 H)
ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 167.2 (C), 164.3 (C),
136.5 (C), 133.5 (C), 131.9 (C), 127.6 (C), 127.1 (CH), 121.8 (CH),
44.3 (CH), 34.4 (CH2), 22.7 (CH2), 22.6 (CH2), 21.2 (CH2), 18.8
(CH3), 18.6 (CH3) ppm. MS (ESI+): m/z = 243 [M + H]+, 265 [M
+ Na]+. HRMS (ESI+): calcd. for [C15H19N2O]+ [M + H]+
243.1492; found 243.1492.
(ESI–): calcd. for [C13H15N2O]– [M
215.1195.
–
H]– 215.1190; found
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra of all new compounds.
Acknowledgments
Compounds 9j and 16a:[13] According to the general procedure
(3 min), the reaction between 1f (93 mg, 0.73 mmol) and 8a (80 mg,
0.74 mmol) afforded first 16a (20 mg, 14%) and then 9j (59 mg,
Financial support from Aix-Marseille Université, the Centre
National de la Recherche Scientifique (CNRS), Departamento Ad-
ministrativo de Ciencia, Tecnología e Innovación (COLCIEN-
43%) as yellow solids. 16a: Rf (40% EtOAc/petroleum ether) =
1
0.65. M.p. 86–87 °C. H NMR (300 MHz, CDCl3): δ = 8.11 (dd, J CIAS), and Universidad del Valle is gratefully acknowledged. M. P.
2344
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2338–2345

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Received: January 27, 2012
Published Online: March 12, 2012
Eur. J. Org. Chem. 2012, 2338–2345
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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