Palladium-catalyzed annulation of acyloximes with arynes (or alkynes): Synthesis of phenanthridines and isoquinolines

Article abstract of DOI:10.1002/anie.200804683

(Chemical Equation Presented) Intermolecular insertion: A palladium-catalyzed domino aminopalladation/C-H functionalization sequence has been developed, and provides access to functionalized phenanthridines and isoquinolines (see scheme; Tf = triflate, TM

Full text of DOI:10.1002/anie.200804683

Communications
DOI: 10.1002/anie.200804683
Domino Reactions
Palladium-Catalyzed Annulation of Acyloximes with Arynes (or
Alkynes): Synthesis of Phenanthridines and Isoquinolines**
Thibaud Gerfaud, Luc Neuville,* and Jieping Zhu*
Palladium-catalyzed carbon–heteroatom bond formation has
been the subject of intense research for the past decades.[1]
Kitamura and Narasaka have developed an elegant palla-
dium-catalyzed carbon–nitrogen bond-forming process by
exploring the chemistry of readily accessible acyloximes.[2] In
multiple bonds was known.[9] In connection with our research
À
program dealing with the transition-metal-catalyzed C X
bond formation[10] and domino processes,[11] we became
interested in exploring the reactivity of the transient
1
2
[12]
= À
{R R C N Pd} species in an intermolecular process. We
report herein the first example of such a process which leads
to a rapid construction of functionalized phenanthridines and
contrast to other palladium-catalyzed reactions where the
[3]
=
nitrogen atom of C N-containing substrates acted as a
À
nucleophile, the acyloximes act firstly as an electrophile to
add oxidatively to the Pd0 complex. The newly generated aza-
palladium(II) complex could then react with internal olefins
to form cyclic product [Scheme 1, Eq. (1)].[4] This novel
isoquinolines by a domino aminopalladation/C H function-
alization sequence.[13] The underlying principle is shown in
Scheme 1 [Eq. (2)]. The intermolecular aminopalladation of
1
2
= À
benzynes (and other alkynes) by a {R R C N Pd} species,
resulting from the oxidative addition of acyloxime to Pd0,
would afford the vinylpalladium intermediate 5. The subse-
À
quent C H functionalization would then provide the cyclic
product.
Benzynes have been widely used in organic synthesis.[14]
Since the seminal work of Guitiꢀn, Perez, and co-workers, it
has been established that arynes participate in palladium-
catalyzed processes[15] and the versatility of such transforma-
tions is rapidly expanding.[16] Combining the unstable and
1
2
= À
reactive {R R C N Pd} species with yet another highly
reactive benzyne intermediate seemed to be a highly
demanding endeavor—as many side reactions of both species
À
are known. However, we expected that the subsequent C H
functionalization step, which would afford the heteroaromatic
compound, could provide the driving force for the overall
heteroannulation process.
We used the reaction of benzophenone O-perfluoroben-
zoyl oxime[17] (3a) with O-(trimethylsilyl)phenyl triflate (7a)
as a probe for evaluating the reaction conditions. Under
reaction conditions previously reported for the carbopallada-
tion of benzynes ([Pd(dba)2] (5 mol%), P(o-tolyl)3 (5 mol%),
CsF (3.0 equiv), in MeCN/toluene 1:9, 1108C for 24 h),[18]
only a trace amount of the desired product 6a was detected
(Table 1, entry 1). A significant amount of triphenylene,
resulting from the palladium-catalyzed cyclotrimerization of
benzyne, was isolated using PdCl2 as a precatalyst (data not
shown). When allylpalladium(II) chloride dimer (APC =
[{(allyl)PdCl}2])[19,20] was used as a precatalyst, analytically
pure phenanthridine 6a was isolated, albeit in low yield
(Table 1, entry 2). Increasing the amount of MeCN in the
solvent system (MeCN/toluene 1:1) increased the yield of
product (Table 1, entries 4 and 5).[21] However, using MeCN
alone as the solvent (at reflux) led to the formation of
triphenylene as a major product and a significant amount of
acyloxime was recovered. Reasoning that the reaction
temperature may be a key factor for the desired trans-
formation, propiononitrile (b.p. 978C) and butyronitrile
(b.p. 115–1178C) were then examined, and the latter was
found to be optimum. This solvent not only allowed a slow
Scheme 1. Palladium-catalyzed transformation of acyloximes.
palladium-catalyzed intramolecular amino-Heck process
allows rapid elaboration of pyrroles,[5] pyridines,[6] and various
aza-heterocycles.[7] This process has recently been used in a
total synthesis of cycloheptylprodigiosin.[8] However, to the
best of our knowledge, this chemistry has been limited to
intramolecular processes and no report on the intermolecular
1
2
= À
trapping of a {R R C N Pd} species by carbon–carbon
[*] T. Gerfaud, Dr. L. Neuville, Dr. J. Zhu
Institut de Chimie des Substances Naturelles, CNRS
91198 Gif-sur-Yvette Cedex (France)
Fax: (+33)1-6907-7247
E-mail: zhu@icsn.cnrs-gif.fr
neuville@icsn.cnrs-gif.fr
Homepage:
http://www.icsn.cnrs-gif.fr/article.php3?id_article=122
[**] Financial support from CNRS and the Institut de Chimie des
Substances Naturelles are gratefully acknowledged. T.G. thanks the
institute for a doctoral fellowships.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200804683.
572
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 572 –577

Angewandte
Chemie
Table 1: A survey of the reaction conditions.[a]
not observed, 5) the presence of
palladium catalyst is necessary,
because in its absence the same
reaction afforded a complex mix-
ture
of
products
(Table 1,
entry 16),[25] 6) during the optimiza-
tion studies 6-propylphenanthridine
(8) was frequently observed as a
side product, especially when xphos
and dppp were used as supporting
ligands.[26] Indeed, compound 8 can
be produced in up to 50% yield
when the oxime was omitted, as
illustrated in Scheme 2. The reac-
tion most probably goes via the h2-
metallocyclopropene intermediate
9[27] which reacted with a second
equivalent of benzyne to form the
palladacycle 10. Subsequent inser-
tion of butyronitrile into 10 would
then afford the observed product 8.
The generality of this novel
Entry
Pd
Ligand
Pd/ligand
Solvent (ratio)
T [8C]
Yield [%][b]
1
2
[Pd(dba)2]
APC
APC
APC
APC
P(o-tolyl)3
P(o-tolyl)3
P(o-tolyl)3
P(o-tolyl)3
xphos
1:1
1:2
1:2
1:2
1:2
CH3CN/tol (1:9)
CH3CN/tol (1:9)
CH3CN/tol (1:9)
CH3CN/tol (1:1)
CH3CN/tol (1:1)
CH3CN
C2H5CN
C3H7CN
C3H7CN
C3H7CN
C3H7CN
C3H7CN
C3H7CN
C3H7CN
C3H7CN
C3H7CN
110
110
110
110
110
80
100
100
120
120
120
120
120
120
120
120
trace
10[g]
trace
27
30
trace
40
40
67
65
53
3[c]
4
5
6[c]
7[d]
8[d]
9[d]
10[d]
11[d]
12[d]
13[d]
14
APC
dppp
APC
P(o-tolyl)3
P(o-tolyl)3
P(o-tolyl)3
1:2
1:2
1:2
–
1:1
1:2
APC[e]
APC
[Pd(PPh3)4]
APC[e]
APC[e]
APC[e]
APC[e]
APC[e]
–
dppp
xphos
–
P(o-tolyl)3
P(o-tolyl)3
–
53
60
70
74
1:2
1:2
15[f]
16
0
domino transformation was exam-
ined by varying the electronic and
steric properties of each reactant,
and the results are summarized in
Table 2. The required ketoxime O-
pentafluorobenzoates were easily
prepared by the condensation of
ketones[28] with hydroxylamine and
[a] All reactions were carried out under an argon atmosphere using Pd (5 mol%), 7a (2 equiv), CsF
(3 equiv), c=0.42m for 20 hours. [b] Yield of isolated product. [c] Slow addition of 7a over 4 h. [d] 7a
(3 equiv) and CsF (4 equiv). [e] 2.5 mol%. [f] c=0.25m in the presence of M.S. (4 ꢀ). [g] Similar yields
were obtained when dppe, P(2-furyl)3, dppp, and johnphos were used as supporting ligands. dba=
trans,trans-dibenzylideneacetone, dppe=ethane-l,2-diylbis(diphenylphosphane), dppp=propane-l,3-
diylbis(diphenylphosphane), johnphos=2-(di-tert-butylphosphino)biphenyl, Tf=triflate, tol=toluene,
TMS=trimethylsilyl, xphos=2-dicyclohexylphosphino-2’,4’,6’-triisopropylbiphenyl.
generation of the benzyne resulting from the poorer solubility
of CsF in butyronitrile (as compared with the solubility in
MeCN), but also allowed us to carry out the reaction at a
higher temperature than the reactions in acetonitrile and
propionitrile (Table 1, entries 8 and 9 versus entries 6 and 7).
By performing the reaction in butyronitrile at reflux in the
presence of 0.025 equivalents of APC, the yield of 6a was not
significantly affected by the structure of the supporting
ligands, and the reaction occurred even without the ligand
(Table 1, entry 13). Nonetheless, P(o-tolyl)3 stood out as the
ligand of choice. The addition of 4-ꢁ molecular sieves (M.S.)
into the mixture further improved the efficiency of the
Scheme 2. Synthesis of 6-propylphenanthridine.
reaction and led to 6a in 74% yield (Table 1, entry 15).
Overall, the optimal reaction conditions were: [{(allyl)PdCl}2]
(2.5 mol%), P(o-tolyl)3 (5 mol%), CsF (3.0 equiv) in butyr-
onitrile (c = 0.42m) at 1208C, in the presence of M.S. (4 ꢁ).
Several points deserved further comment regarding this
transformation: 1) less reactive benzophenone O-benzoylox-
ime was a poor substrate that afforded a low yield of the
annulation product, 2) use of the butyronitrile soluble tetra-
butylammonium triphenyldifluorosilicate (TBAT), instead of
CsFonly led to the formation of triphenylene and degradation
products, 3) the Beckmann rearrangement product was not
isolated under the optimized reaction conditions,[22] 4) we
were initially concerned that the product might interfere with
benzyne because a variety of nitrogen-containing hetero-
cycles, including pyridines[23] and quinolines,[24] have been
shown to react with benzynes, however, this side reaction was
subsequent acylation with pentafluorobenzoyl chloride.
Symmetrical 4,4’-substituted benzophenone-derived
oximes bearing electron-withdrawing groups smoothly under-
went the annulation process to generate the expected
phenanthridines (Table 2, entries 1–4). In the case of 3c, an
appreciable amount of ketone was isolated, thus explaining
the somewhat reduced yield of 6c (Table 2, entry 2). The
presence of a chlorine atom did not alter the reaction
pathway, thus indicating that acyloxime 3 is more prone to
undergo oxidative addition to Pd0 than the aryl chloride
(Table 2, entry 3). A weakly electron-donating methyl group
was tolerated in the reaction (Table 2, entry 5), but a strongly
electron-donating group like a methoxy group was incompat-
ible with the domino sequence as no desired compound could
Angew. Chem. Int. Ed. 2009, 48, 572 –577
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
573

Communications
Table 2: Scope of the palladium-catalyzed annulations.[a]
Entry Oxime
Aryne Product
Yield
[%][b]
Entry
Oxime
Aryne
Product
Yield
[%][b]
(E)- or (Z)-3h:
1
7a
69
7
7a
67
R1 =NO2, R2 =OMe
2
3
3c: R1 =R2 =CF3
7a
6c: R1 =R2 =CF3
43
66
8
9
7a
41
43
3d: R1 =R2 =Cl
7a
6d: R1 =R2 =Cl
7a
4
5
3e: R1 =R2 =CN
7a
7a
6e: R1 =R2 =CN
70
30
10
11
3a
3a
67
51
3 f: R1 =R2 =CH3
6 f: R1 =R2 =CH3
6
7a
45
12
3a
44
[a] All reactions were carried out under an argon atmosphere using benzyne precursor (7; 2 equiv), CsF (3 equiv), c=0.42m in the presence of M.S.
(4 ꢀ) for 24 hours. [b] Yield of isolated product.
be isolated (not shown). When meta-substituted 3,3’-trifluoro-
methyl 3g was employed, 8-(trifluoromethyl)phenanthridine
6g was obtained at the expense of 10-(trifluoromethyl)phe-
nanthridine, possibly because of steric reason (Table 2,
entry 6). 2,2’-dithienyl and -dibenzofuranyl acylketoximes 3j
and 3k have also successfully been employed in this reaction,
thus affording reasonable yields of the corresponding hetero-
cyclic compounds (Table 2, entries 8 and 9). These results are
574
www.angewandte.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 572 –577

Angewandte
Chemie
noteworthy as both the starting materials and the products
could act as ligands to sequester the palladium catalyst.
Unsymmetrical acylketoximes were also evaluated. In the
case of 3h, bearing two groups that have opposing electronic
properties, the reaction proceeded with good overall yield:
À
the C H annulation step occurring on both electron-rich and
electron-poor aryl group, and afforded 6h and 6i in a 1:1 ratio
Scheme 4. Synthesis of dimethyl isoquinoline-3,4-dicarboxylates.
(Table 2, entry 7).[29]
Substituted O-(trimethylsilyl)aryl triflates were also
briefly examined. 4,5-dimethyl-2-(trimethylsilyl)phenyl tri-
flate (7b) and 3-(trimethylsilyl)naphthalen-2-yl triflate (7c)
furnished the desired product 6l and 6m in 67 and 51% yields,
respectively (Table 2, entries 10 and 11). When the 3-
methoxy-2-trimethylsilyl trifluorosulfonate (7d) reacted
with benzophenone O-perfluorobenzoyl oxime (3a), two
isomers (6n and 6o) were obtained in a 2.2:1 ratio (Table 2,
entry 12). Similar results were obtained when 3a reacted with
2-methoxy-6-trimethylsilyl trifluorosulfonate (7e), which is a
regioisomer of 7d. These results clearly suggest the interme-
diacy of an aryne species in the annulation process.[30]
Acetophenone-type acyloximes bearing an aryl and an
alkyl group (3p–3r) were also subjected to the domino
process (Scheme 3). They proved to be poor substrates and
Scheme 5. Possible reaction pathways of the domino aminopallada-
À
tion/C H functionalization sequence.
À
Narasaka, oxidative insertion of palladium into the N O
bond of an acyloxime should lead to compound A. Two
possible pathways can then be considered: 1) cis-Amino-
palladation of benzyne or alkyne species would generate a
second PdII intermediate B that could evolve into complex C
Scheme 3. Synthesis of 6-alkylphenanthridines.
À
by an intramolecular C H activation process. A reductive
elimination would close the catalytic cycle thereby producing
afforded the expected phenanthridines in low yields. Since the
the nitrogen-containing heterocycles. 2) Alternatively, a
= À
angle of the C N M moiety is almost linear, the geometry of
cyclopalladated intermediate B’ could be formed from com-
plex A. Such a complex is related to the numerous aza-
palladacycles which are well documented,[33] even if they
usually bear a neutral nitrogen ligand. Triple bond insertion
into complex B’ could then lead to intermediate C, which after
reductive elimination would afford the annulated compound.
Another catalytic cycle involving the h2-metallocyclopropene
intermediate 9 may also be operative (see Scheme 2).[34]
However, we believed that this kinetically viable pathway
might not be responsible for the formation of the desired
product.[35] Rather, it accounts for the formation of the side
products such as triphenylene and 6-propylphenanthridine.
In summary, we have developed a novel palladium-
catalyzed domino annulation process for the formation of
biologically relevant phenanthridines and isoquinolines. To
the best of our knowledge, this represented the first example
the starting N-acyloxime should not be a concern. Indeed,
control experiments using geometrically pure acyloxime (E)-
3h and (Z)-3h afforded the same ratio of compounds 6h and
6i (Table 2, entry 7). We hypothesized that the presence of an
enolizable alkyl substituent provided an opportunity for
imine–enamine tautomerization, which could in turn led to
some unproductive reaction pathways.[31]
Encouraged by the successful reaction between benzynes
and acyloximes, the reaction of 3a with dimethyl acetylene-
dicarboxylate (DMAD) was next examined. The best reaction
conditions consisted of APC as a catalyst under microwave
irradiation conditions.[32] Under optimal reaction conditions
(APC, butyronitrile, MW, 1508C), the desired isoquinoline
12a was isolated in 50% yield (Scheme 4). The addition of
ligand reduced the yield of 12a, while the presence of CsF led
to a complete degradation of the starting materials. Unfortu-
nately, diphenylacetylene failed to participate in this annula-
tion reaction.
1
2
= À
wherein a {R R C N Pd} species generated by oxidative
addition of acyloxime to Pd0 underwent intermolecular
aminopalladation reaction of alkynes. The use of butyronitrile
as the solvent was determinant to the success of the present
A possible scenario that could account for the formation
of phenanthridine 6 and isoquinoline 12 is illustrated in
Scheme 5. According to the proposal by Kitamura and
À
aminopalladation/C H functionalization process and we
assumed that it could well be an effective solvent in other
Angew. Chem. Int. Ed. 2009, 48, 572 –577
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
575

Communications
2005, 7, 609 – 611; isoxazolines: f) P. J. Thomas, A. T. Axtell, J.
Klosin, W. Peng, C. L. Rand, T. P. Clark, C. R. Landis, K. A.
Abboud, Org. Lett. 2007, 9, 2665 – 2668.
palladium-catalyzed transformations involving benzyne inter-
mediates.
[8] A. Fꢃrstner, K. Radkowski, H. Peters, Angew. Chem. 2005, 117,
2837 – 2841; Angew. Chem. Int. Ed. 2005, 44, 2777 – 2781.
[9] The copper-catalyzed reaction of acyloxime involving intermo-
lecular transmetalation with boronic acid is known, see: S. Liu,
L. S. Liebeskind, J. Am. Chem. Soc. 2008, 130, 6918 – 6919.
[10] a) F. Bonnaterre, M. Bois-Choussy, J. Zhu, Org. Lett. 2006, 8,
4351 – 4354; b) A. Salcedo, L. Neuville, J. Zhu, J. Org. Chem.
2008, 73, 3600 – 3603.
Experimental Section
Typical procedure for the synthesis of phenanthridines: Benzophe-
none O-pentafluorobenzoyloxime 3a (100 mg, 0.255 mmol, 1.0 equiv)
and tri(o-tolyl)phosphine (3.9 mg, 0.013 mmol, 0.05 equiv) were
added to
a
stirred suspension of [{(allyl)PdCl}2] (2.3 mg,
0.006 mmol, 0.025 equiv) and molecular sieves (4 ꢁ) in freshly
distilled and degassed butyronitrile (0.6 mL) under argon. Then
anhydrous CsF (116.4 mg, 0.770 mmol, 3.0 equiv) and 2-(trimethylsi-
lyl)phenyltriflate 7a (152.5 mg, 0.510 mmol, 2.0 equiv) were added.
After stirring at reflux overnight, the reaction mixture was diluted
with water and the aqueous phase was extracted with EtOAc. The
combined organic extracts were washed with a saturated solution of
NH4Cl, dried over sodium sulfate and concentrated under reduced
pressure. Purification by flash column chromatography on silica gel
(dichloromethane) afforded 6-phenylphenantridine 6a as a white
solid (49 mg, 74%).
[11] a) G. Cuny, M. Bois-Choussy, J. Zhu, Angew. Chem. 2003, 115,
4922 – 4925; Angew. Chem. Int. Ed. 2003, 42, 4774 – 4777; b) G.
Cuny, M. Bois-Choussy, J. Zhu, J. Am. Chem. Soc. 2004, 126,
14475 – 14484; c) A. Pinto, L. Neuville, P. Retailleau, J. Zhu, Org.
Lett. 2006, 8, 4927 – 4930; d) A. Pinto, L. Neuville, P. Retailleau,
J. Zhu, Angew. Chem. 2007, 119, 3355 – 3359; Angew. Chem. Int.
Ed. 2007, 46, 3291 – 3295; e) A. Pinto, Y. Jia, L. Neuville, J. Zhu,
Chem. Eur. J. 2007, 13, 961 – 967; f) A. Salcedo, L. Neuville, C.
Rondot, P. Retailleau, J. Zhu, Org. Lett. 2008, 10, 857 – 860.
[12] Only limited examples of catalytic intermolecular aminopalla-
dation of alkynes (alkenes) that involve amides, carbamates, and
sulfonamides are known; for general reviews, see: a) S. Cacchi,
G. Fabrizi, Chem. Rev. 2005, 105, 2873 – 2920; b) A. Minatti, K.
Muꢄiz, Chem. Soc. Rev. 2007, 36, 1142 – 1152; for recent
examples, see: c) T. Shimada, Y. Yamamoto, J. Am. Chem. Soc.
2002, 124, 12670 – 12671; d) S. Tang, P. Peng, S.-F. Pi, Y. Liang, N.-
X. Wang, J.-H. Li, Org. Lett. 2008, 10, 1179 – 1182; for selected
aminopalladation of alkenes and dienes, see: e) T. Hosokawa, M.
Takano, Y. Kuroki, S.-I. Murahashi, Tetrahedron Lett. 1992, 33,
6643 – 6646; f) V. I. Timokhin, N. R. Anastasi, S. S. Stahl, J. Am.
Chem. Soc. 2003, 125, 12996 – 12997; g) G. L. J. Bar, G. C. Lloyd-
Jones, K. I. Booker-Milburn, J. Am. Chem. Soc. 2005, 127, 7308 –
7309; h) H. Du, B. Zhao, Y. Shi, J. Am. Chem. Soc. 2007, 129,
762 – 763; for a review on aza-Wacker reactions, see: i) V. Kotov,
C. C. Scarborough, S. S. Stahl, Inorg. Chem. 2007, 46, 1910 –
1923.
Received: September 24, 2008
Published online: December 9, 2008
Keywords: arynes · domino reactions · heterocycles · oximes ·
.
palladium
[1] a) J. F. Hartwig in Handbook of Organopalladium Chemistry for
Organic Synthesis, Vol. 1 (Eds.: E.-I. Negishi, A. de Meijere),
Wiley-Interscience, New York, 2002, pp. 1051 – 1096; b) A. R.
Muci, S. L. Buchwald in Topics in Current Chemistry, Vol. 219
(Ed.: N. Miyaura), Springer, Berlin, 2002, pp. 133 – 205; c) S. L.
Buchwald, C. Mauger, G. Mignani, U. Scholz, Adv. Synth. Catal.
2006, 348, 23 – 39.
[2] a) M. Kitamura, K. Narasaka, Chem. Rec. 2002, 2, 268 – 277;
b) K. Narasaka, M. Kitamura, Eur. J. Org. Chem. 2005, 4505 –
4519.
À
[13] For recent reviews dealing with C H activation, see: a) L.-C.
Campeau, K. Fagnou, Chem. Commun. 2006, 1253- 1264; b) D.
Alberico, M. E. Scott, M. Lautens, Chem. Rev. 2007, 107, 174 –
=
[3] Selected C N-containing coupling partner: benzophenone
À
238; for a monograph, see: Handbook of C H Transformations
imine a) J. P. Wolfe, J. Khman, J. P. Sadighi, R. A. Singer, S. L.
Buchwald, Tetrahedron Lett. 1997, 38, 6367 – 6370; b) G. Mann,
J. F. Hartwig, M. S. Driver, C. Fernandez-Rivas, J. Am. Chem.
Soc. 1998, 120, 827 – 828; sulfoximines: c) C. Bolm, J. P. Hilde-
brand, J. Org. Chem. 2000, 65, 169 – 175; N-trialkylsilylimines:
d) J. Barluenga, F. Aznar, C. Valdꢂs, Angew. Chem. 2004, 116,
347 – 349; Angew. Chem. Int. Ed. 2004, 43, 343 – 345.
(Ed.: G. Dyker), Wiley-VCH, Weinheim, 2005.
[14] For reviews on arynes, see: a) S. Saito, Y. Yamamoto, Chem. Rev.
2000, 100, 2901 – 2916; b) H. H. Wenk, M. Winkler, W. Sander,
Angew. Chem. 2003, 115, 518 – 546; Angew. Chem. Int. Ed. 2003,
42, 502 – 528; c) H. Pellissier, M. Santelli, Tetrahedron 2003, 59,
701 – 730; d) R. Sanz, Org. Prep. Proced. Int. 2008, 40, 215 – 291.
[15] a) D. Peꢄa, S. Escudero, D. Pꢂrez, E. Guitiꢅn, L. Castedo,
Angew. Chem. 1998, 110, 2804 – 2806; Angew. Chem. Int. Ed.
1998, 37, 2659 – 2661; for a review, see: b) E. Guitiꢀn, D. Pꢂrez,
D. Peꢄa in Topics in Organometallic Chemistry, Vol. 14 (Ed.: J.
Tsuji), Springer, Weinheim, 2005, pp. 109 – 146.
À
[4] b C C bond cleavage from alkylideneaminopalladium(II) spe-
cies have also been reported: a) T. Nishimura, S. Uemura, J. Am.
Chem. Soc. 2000, 122, 12049 – 12050; b) T. Nishimura, Y.
Nishiguchi, Y. Maeda, S. Uemura, J. Org. Chem. 2004, 69,
5342 – 5347.
[16] a) K. V. Radhakrishnan, E. Yoshikawa, Y. Yamamoto, Tetrahe-
dron Lett. 1999, 40, 7533 – 7535; b) D. Peꢄa, S. Escudero, D.
Pꢂrez, E. Guitiꢅn, L. Castedo, J. Am. Chem. Soc. 1999, 121,
5827 – 5828; c) E. Yoshikawa, Y. Yamamoto, Angew. Chem.
2000, 112, 185 – 187; Angew. Chem. Int. Ed. 2000, 39, 173 – 175;
d) D. Peꢄa, D. Pꢂrez, D. E. Guitiꢀn, L. Castedo, J. Org. Chem.
2000, 65, 6944 – 6950; e) N. Chatani, A. Kamitani, M. Oshita, Y.
Fukumoto, S. Murai, J. Am. Chem. Soc. 2001, 123, 12686 – 12687;
f) Y. Sato, T. Tamura, M. Mori, Angew. Chem. 2004, 116, 2490 –
2494; Angew. Chem. Int. Ed. 2004, 43, 2436 – 2440; g) M.
Jeganmohan, C. H. Cheng, Org. Lett. 2004, 6, 2821 – 2824;
h) C. H. Cheng, M. Jeganmohan, Synthesis 2005, 1693 – 1697;
i) T. T. Jayanth, M. Jeganmohan, C. H. Cheng, Org. Lett. 2005, 7,
2921 – 2924; j) J. L. Henderson, A. S. Edwards, M. F. Greaney, J.
Am. Chem. Soc. 2006, 128, 7426 – 7427; k) Z. J. Liu, R. C.
[5] a) H. Tsutsui, K. Narasaka, Chem. Lett. 1999, 45 – 56; b) H.
Tsutsui, K. Narasaka, M. Kitamura, Bull. Chem. Soc. Jpn. 2002,
75, 1451 – 1460; c) J. Ichikawa, K. Sakoda, J. Mihara, N. Ito, J.
Fluorine Chem. 2006, 127, 489 – 504; d) S. Zaman, M. Kitamura,
A. D. Abell, Aust. J. Chem. 2007, 60, 624 – 626; e) J.-L. Zhu, Y.-
H. Chan, Synlett 2008, 1250 – 1254.
[6] a) H. Tsutsui, K. Narasaka, Chem. Lett. 2001, 526 – 527; b) M.
Kitamura, D. Kudo, K. Narasaka, ARKIVOC 2006, Part (iii),
148 – 162.
[7] a) M. Kitamura, S. Zaman, K. Narasaka, Synlett 2001, 974 – 976;
b) M. Kitamura, S. Chiba, O. Saku, K. Narasaka, Chem. Lett.
2002, 606 – 607; c) S. Zaman, M. Kitamura, K. Narasaka, Bull.
Chem. Soc. Jpn. 2003, 76, 1055 – 1062; d) S. Chiba, M. Kitamura,
O. Saku, K. Narasaka, Bull. Chem. Soc. Jpn. 2004, 77, 785 – 796;
imidazoles: e) S. Zaman, K. Mitsuru, A. D. Abell, Org. Lett.
576
www.angewandte.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 572 –577

Angewandte
Chemie
Larock, Angew. Chem. 2007, 119, 2587 – 2590; Angew. Chem. Int.
Ed. 2007, 46, 2535 – 2538; l) Z. J. Liu, R. C. Larock, Tetrahedron
2007, 63, 347 – 355; m) Y. Sato, T. Tamura, A. Kinbara, M. Mori,
Adv. Synth. Catal. 2007, 349, 647 – 661; n) C. S. Xie, Y. H. Zhang,
Z. D. Huang, P. X. Xu, J. Org. Chem. 2007, 72, 5431 – 5434.
[17] Y. Himeshima, T. Sonoda, H. Kobayashi, Chem. Lett. 1983,
1211 – 1214.
[28] Some ketones were prepared according to: P.-A. Enquist, P.
Nilsson, M. Larhed, Org. Lett. 2003, 5, 4875 – 4878.
[29] a) D. Garcia-Cuadrado, A. A. C. Braga, F. Maseras, A. M.
Echavarren, J. Am. Chem. Soc. 2006, 128, 1066 – 1067; b) F.
Bonnaterre, M. Bois-Choussy, J. Zhu, Beilstein J. Org. Chem.
2008, 4, 1 – 6. Note that no annulation product was formed in the
case of bis(4-methoxyphenyl)methanone acyloxime.
[18] Z. Liu, X. Zhang, R. C. Larock, J. Am. Chem. Soc. 2005, 127,
15716 – 15717.
[30] We thank the referee for suggesting this control experiment; see
also: a) T. T. Jayanth, M. Jeganmohan, M.-J. Cheng, S.-Y. Chu,
C.-H. Cheng, J. Am. Chem. Soc. 2006, 128, 2232 – 2233; b) I.
Quintana, A. J. Boersma, D. Peꢄa, D. Pꢂrez, E. Guitiꢅn, Org.
Lett. 2006, 8, 3347 – 3349.
[31] a) C. M. P. Ferreira, M. Fꢅtina, C. Guesda de Silva, V. Y.
Kukushkin, J. J. R. Frafflsto da Silva, A. J. L. Pombeiro, J.
Chem. Soc. Dalton Trans. 1998, 325 – 326; b) V. Y. Kukushkin,
A. J. L. Pombeiro, Coord. Chem. Rev. 1999, 181, 147 – 175; c) A.
Tillack, P. Arndt, A. Spannenberg, R. Kempe, U. Rosenthal, Z.
Anorg. Allg. Chem. 1998, 624, 737 – 740.
[32] Microwave experiments were conducted by using a Discover
microwave reactor from CEM. All experiments were performed
in sealed tubes under an argon atmosphere. Microwave irradi-
ation of 300 W was used, the temperature was ramped from
room temperature to 1508C in 1 minute. Once this temperature
was reached, the reaction mixture was held at 1508C for the
indicated time. For recent reviews, see: a) C. O. Kappe, Angew.
Chem. 2004, 116, 6408 – 6443; Angew. Chem. Int. Ed. 2004, 43,
6250 – 6284; b) A. de La Hoz, A. Diaz-Ortiz, A. Moreno, Chem.
Soc. Rev. 2005, 34, 164 – 178.
[19] CsF is able to reduce PdII to Pd0, see: M. R. Mason, J. G.
Verkade, Organometallics 1992, 11, 2212 – 2220.
[20] For reduction of the [{(allyl)PdCl}2], see: S. E. Denmark, R. C.
Smith, Synlett 2006, 2921 – 2928; and references therein.
[21] For an exemple of solvent induced divergent behavior, see: E.
Yoshikawa, K. V. Radhakrishnan, Y. Yamamoto, J. Am. Chem.
Soc. 2000, 122, 7280 – 7286.
[22] For a review, see: R. E. Gawly, Org. React. 1988, 35, 1 – 420.
[23] a) E. K. Fields, S. Meyerson, J. Org. Chem. 1966, 31, 3307 – 3309;
b) N. Dennis, A. R. Katritzky, S. K. Parton, J. Chem. Soc. Perkin
Trans. 1 1976, 2285 – 2288; c) D. K. Rayabarapu, K. K. Majum-
dar, T. Sambaiah, C.-H Cheng, J. Org. Chem. 2001, 66, 3646 –
3649.
[24] M. Jeganmohan, C.-H. Cheng, Chem. Commun. 2006, 2454 –
2456.
[25] Microwave- or light-induced transformation of oximes deriva-
tives to phenanthridines or isoquinolines have been reported:
a) R. Alonso, P. J. Campos, B. Garcia, M. A. Rodriguez, Org.
Lett. 2006, 8, 3521 – 3523; b) F. Portela-Cubillo, J. S. Scott, J. C.
Walton, J. Org. Chem. 2008, 73, 5558 – 5565.
[26] Very recently, cyclocondensation between arynes and nitriles
have been reported under nickel catalysis conditions: J.-C.
Hsieh, C.-H. Cheng, Chem. Commun. 2008, 2992 – 2994.
[27] M. Retboll, A. J. Edwards, A. D. Rae, A. C. Willis, M. A.
Bennett, E. Wenger, J. Am. Chem. Soc. 2002, 124, 8348 – 8360.
[33] For a recent review, see: J. Dupont, C. S. Consorti, J. Spencer,
Chem. Rev. 2005, 105, 2527 – 2572.
[34] a) Ref: [18] and b) J. L. Henderson, A. S. Edwards, M. F. Grea-
ney, Org. Lett. 2007, 9, 5589 – 5592.
[35] H. Yoshida, K. Tanino, J. Ohshita, A. Kunai, Angew. Chem. 2004,
116, 5162 – 5165; Angew. Chem. Int. Ed. 2004, 43, 5052 – 5055.
Angew. Chem. Int. Ed. 2009, 48, 572 –577
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
577