An allylpalladium(IV) intermediate in the synthesis of highly substituted benzoxepines and benzopyrans via reactions of stable pallada(II)cycles with allyl bromides

Article abstract of DOI:10.1021/om7002865

Stable pallada(II)cycles L₂Pd-1-C₆H ₅-2-OCHCO₂Et, featuring a Pd-bonded sp³- hybridized stereogenic carbon and bipyridine or bis(imine) auxiliary ligands (L-L), reacted with allyl bromides via a Pd(II)Pd(IV)-mediated process involving a direct C(sp²)-H functionalization to afford highly substituted benzoxepines or benzopyrans. An allylpalladium(IV) complex, which was detected by low-temperature ¹H NMR analysis and characterized by X-ray crystallography, was shown to operate as an intermediate in the reaction sequence.

Full text of DOI:10.1021/om7002865

3874
Organometallics 2007, 26, 3874-3883
An Allylpalladium(IV) Intermediate in the Synthesis of Highly
Substituted Benzoxepines and Benzopyrans via Reactions of Stable
Pallada(II)cycles with Allyl Bromides
Ruiyun Guo, Janelle L. Portscheller, Victor W. Day, and Helena C. Malinakova*
Department of Chemistry, UniVersity of Kansas, 1251 Wescoe Hall DriVe, Lawrence, Kansas 66045
ReceiVed March 25, 2007
Stable pallada(II)cycles L2Pd-1-C6H5-2-OCHCO2Et, featuring a Pd-bonded sp3-hybridized stereogenic
carbon and bipyridine or bis(imine) auxiliary ligands (L-L), reacted with allyl bromides via a Pd(II)-
Pd(IV)-mediated process involving a direct C(sp2)-H functionalization to afford highly substituted
benzoxepines or benzopyrans. An allylpalladium(IV) complex, which was detected by low-temperature
1H NMR analysis and characterized by X-ray crystallography, was shown to operate as an intermediate
in the reaction sequence.
acterized, and shown to participate in the overall C-H func-
Introduction
1
tionalization sequences.5 Earlier, H NMR data for a Pd(IV)
Multistep cascade reactions catalyzed by palladium complexes
are extremely useful tools in organic synthesis.1 The traditional
processes rely on catalytic cycles featuring palladium in
oxidation states Pd(0) and Pd(II) and in most cases exploit
intermediates with C(sp2)-Pd bonds.1 Recent developments
have suggested that reactions involving Pd(IV) intermediates
could give rise to synthetically attractive transformations.2,3
Palladium(IV) complexes have been previously detected
spectroscopically,4a,g isolated,4b,d,h,k and in some cases character-
ized by X-ray crystallography.4b,c,e,i,l,m However, the successful
isolation and unambiguous characterization of a Pd(IV) inter-
mediate, which could be converted into a complex organic
molecule, remain extremely rare. Most recently, stable Pd(IV)
intermediates arising via oxidation of Pd(II) complexes with
hypervalent iodonium electrophiles have been isolated, char-
complex generated via oxidative addition with benzyl bromide
were reported,6a providing support for the proposed involvement
of analogous catalytic intermediates in synthetically useful Pd-
catalyzed cyclizations.6b Aiming to explore a formal annulation
between two polyfunctional organic electrophiles, we envisioned
that the hypothetical Pd(IV) intermediate I (Figure 1) with three
C-Pd bonds, including a Pd-bonded stereogenic center, and
an organic fragment featuring a reactive functional group (e.g.,
a double bond) could be generated and subsequently collapse
to afford complex cyclic molecules with multiple stereogenic
centers.
Herein, we provide a proof of concept for such a protocol,
including the evidence for the formation of the proposed Pd-
(IV) intermediate I via oxidative addition of allyl bromides to
the Pd(II) complexes II (Figure 1).7 The stable palladacycles
II, possessing a Pd-bonded sp3-hybridized stereogenic carbon,
reacted with allyl bromides to afford good yields of highly
substituted benzoxepines IV and V or benzopyrans VI through
a sequential formation of up to three C-C bonds, including a
C(sp2)-H functionalization event (Figure 1). Under optimized
conditions, the Pd-bonded stereocenter in intermediates I and
II was incorporated into the organic products V and VI.
Spectroscopic data (low-temperature 1H NMR) as well as X-ray
crystallographic evidence confirmed the involvement of the
reactive Pd(IV) intermediate I bearing the bipyridine ligand (L-
L) in the reaction sequence. Structures of complexes III bearing
both bipyridine and bis(imine) ligands and arising via C(sp2)-
C(sp3) bond-forming reductive elimination from the Pd(IV)
intermediates I were established by X-ray crystallography, and
* To whom correspondence should be addressed. E-mail: hmalina@ku.edu.
(1) Balme, G.; Bossharth, E.; Monteiro, N. Eur. J. Org. Chem. 2003,
4101.
(2) (a) Hull, K. L.; Lanni, E. L.; Sanford, M. S. J. Am. Chem. Soc. 2006,
128, 1407. (b) Kalyani, D.; Deprez, N. R.; Desai, L. V.; Sanford, M. S. J.
Am. Chem. Soc. 2005, 127, 7330. (c) Dick, A. R.; Hull, K. L.; Sanford, M.
S. J. Am. Chem. Soc. 2004, 126, 2300. A Pd(IV) intermediate was proposed
for the arylation of C-H bonds with aryl iodides, see: (d) Zaitsev, V. G.;
Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2005, 127, 13154.
(3) (a) Jafarpour, F.; Lautens, M. Org. Lett. 2006, 8, 3601. (b) Catellani,
M. Synlett 2003, 298.
(4) For examples of studies stoichiometric in palladium, in which distinct
Pd(IV) complexes were isolated or detected in solution, using aryl or alkynyl
hypervalent iodonium oxidants, alkyl or benzyl halides, propargyl bromides,
diaryl diselenide or halogens, see: (a) Canty, A. J.; Rodemann, T.; Skelton,
B. W.; White, A. H. Organometallics 2006, 25, 3996. (b) Dick, A. R.;
Kampf, J. W.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127, 12790. (c)
Campora, J.; Palma, P.; del Rio, D.; Lopez, J. A.; Valerga, P. Chem.
Commun. 2004, 1490. (d) Canty, A. J.; Patel, J.; Rodemann, T.; Ryan, J.
H.; Skelton, B. W.; White, A. H. Organometallics 2004, 23, 3466. (e)
Yamamoto, Y.; Kuwabara, S.; Matsuo, S.; Ohno, T.; Nishiyama, H.; Itoh,
K. Organometallics 2004, 23, 3898. (f) Canty, A. J.; Denney, M. C.; Patel,
J.; Sun, H.; Skelton, B. W.; White, A. H. J. Organomet. Chem. 2004, 689,
672. (g) van Belzen, R.; Elsevier, C. J.; Dedieu, A.; Veldman, N.; Spek, A.
L. Organometallics 2003, 22, 722. (h) Canty, A. J.; Jin, H.; Penny, J. D. J.
Organomet. Chem. 1999, 573, 30. (i) Canty, A. J.; Hoare, J. L.; Patel, J.;
Pfeffer, M.; Skelton, B. W.; White, A. H. Organometallics 1999, 18, 2660.
(j) Canty, A. J. Acc. Chem. Res. 1992, 25, 83 and references cited therein.
(k) Byers, P. K.; Canty, A. J. J. Chem. Soc., Chem. Commun. 1988, 639.
(l) Byers, P. K.; Canty, A. J.; Skelton, B. W.; White, A. H. J. Chem. Soc.,
Chem. Commun. 1987, 1093. (m) Byers, P. K.; Canty, A. J.; Skelton, B.
W.; White, A. H. J. Chem. Soc., Chem. Commun. 1986, 1722.
(5) Dick, A. R.; Kampf, J. W.; Sanford, M. S. J. Am. Chem. Soc. 2005,
127, 12790.
(6) (a) Bocelli, G.; Catellani, M.; Ghelli, S. J. Organomet. Chem. 1993,
458, C12. (b) However, an alternative mechanistic pathway relying on
transmetalation between two Pd(II) centers and lacking the involvement of
Pd(IV) intermediates in analogous Pd-catalyzed reactions involving aryl
halides as hypothetical oxidants for Pd(II) complexes was proposed and
supported by computational studies; see: Cardemas. D. J.; Martin-Matute,
B.; Echavarren, A. M. J. Am. Chem. Soc. 2006, 128, 5033.
(7) For rare reports on reactions of pallada(II)cycles with 2-propenyl
bromide, leading to the in situ (1H NMR) detection of a presumed Pd(IV)
complex, see: (a) Canty, A. J.; Hoare, J. L.; Davies, N. W.; Trail, P. R.
Organometallics 1998, 17, 2046. (b) de Graaf, W.; Boersma, J.; van Koten,
G. Organometallics 1990, 9, 1479.
10.1021/om7002865 CCC: $37.00 © 2007 American Chemical Society
Publication on Web 06/19/2007

An Allylpalladium(IV) Intermediate
Organometallics, Vol. 26, No. 15, 2007 3875
Table 1.
allyl bromide
entry R1 R2
product (% yield)
solvent/
additive
time (h)/
temp (°C)
1
2
3
4
5
6
7
8
H
COOMe DCE/t-BuOKb
20/95
1.5/85
2/95
2/115
60/115
3/100
60/105
2/115
4a (53)
NA/NaBra
4a (50)c 6 (15)
4a (62)
a
NA/Cs2CO3
NA/Cs2CO3
b
H
Me
4b (29)d 5a (35)
4b (40)d 5a (18)
5b (58)
b
MeCN/Cs2CO3
a
Figure 1. Overview of the results.
Me COOMe NA/Cs2CO3
Me Me
b
DCE/Cs2CO3
7 (56)
DCE/t-BuOKb
5c (28) 5d (14)
Scheme 1
a Method A: in neat allyl bromide, w/o Cs2CO3 (2.5 equiv) or t-BuOK
(3.5 equiv) or NaBr (2.0 equiv). b Method B: in solution with Cs2CO3 (2.5
equiv) or t-BuOK (3.5 equiv). c Trace of benzoxepine lacking the allyl
substituent in the aromatic ring was isolated.10 d Trace of a disubstituted
benzene was isolated.11
heterocycles 4, 5, and 7 in a single step (Table 1). It is notable
that 2 equiv of the allylic electrophiles participated in the
cyclization, resulting in functionalization of a C(sp2)-H bond
in the aromatic rings (vide infra). Bases and/or additives were
employed to facilitate the intramolecular cyclization presumably
terminated by â-hydride elimination (vide infra). The best results
in the reaction of palladacycle 3a with methyl 4-bromo-2-
butenoate were achieved in neat allyl bromide in the presence
of Cs2CO3, providing the benzoxepine 4a (62%) as a single
product via an unexpected 7-endo-trig cyclization (entry 3 of
Table 1).9 In the presence of NaBr, benzoxepine 4a (50%) was
accompanied by traces of a benzoxepine lacking the second allyl
substituent in the aromatic ring10 and the phenol 6 (15%) (entry
2 of Table 1). The reaction in solution (1,2-dichloroethane)
afforded benzoxepine 4a in a lower yield (53%; entry 1 of Table
1) as a single product. Palladium was recovered as complex 8
(45% yield; Chart 1) from reactions run in neat allyl bromides
via precipitation with methylene chloride and as complex 9 (11%
yield; Chart 1) after chromatographic separation of the meth-
complexes III were converted to the functionalized heterocycles
IV-VI under suitable conditions. The study documents the key
elemental events of the multistep sequence and demonstrates
the synthetic potential of reaction cascades exploiting Pd(0)-
Pd(II)-Pd(IV) cycles.
Results and Discussion
The stable palladacycle 3a, featuring a palladium-bonded sp3-
hybridized stereogenic carbon and the N,N′-dicyclohexylethyl-
enediimine ligand, was prepared from aryl iodide 1 via complex
2a by an established method8 (Scheme 1), and the molecular
structure of palladacycle 3a was confirmed by X-ray crystal-
lography. Palladacycle 3a was treated with substituted allyl
bromides at elevated temperatures (80-100 °C), either in
solution (6-10 equiv of allyl bromides in 1,2-dichloroethane
or acetonitrile) or in neat allyl bromide, to afford the racemic
(9) For examples of relatively rare 7-endo Heck reactions, and a
discussion of the competition between 7-endo and 6-exo cyclization
pathways in the Heck reactions, see: (a) Rigby, J. H.; Hughes, R. C.; Heeg,
M. J. J. Am. Chem. Soc. 1995, 117, 7834. (b) Gibson, S. E.; Middleton, R.
J. J. Chem. Soc., Chem. Commun. 1995, 1743.
(10) The benzoxepine with the structure shown below was isolated and
1
identified by H and 13C NMR spectroscopy.
(8) Pd(II) complexes bearing bipyridine and other N-based auxiliary
ligands were frequently employed in the studies generating Pd(IV)
complexes.4 For the method for the preparation of complexes 2 and 3, see:
(a) Lu, G.; Malinakova, H. C. J. Org. Chem. 2004, 69, 4701. (b) Portscheller,
J. L.; Malinakova, H. C. Org. Lett. 2002, 4, 3679.

3876 Organometallics, Vol. 26, No. 15, 2007
Guo et al.
Chart 1
ylene chloride extracts of the crude precipitate. Structures of
complexes 8 and 9 were determined by X-ray crystallography.
Replacement of the activating ester group with a methyl
substituent or the presence of an additional terminal methyl
group in the allyl bromide favored the 6-exo-trig cyclization
leading to benzopyrans 5 and 7 (entries 4-8 of Table 1).9
Treatment of palladacycle 3a with the least hindered 1-bromo-
2-butene in neat allyl bromide afforded comparable quantities
of the 7-endo and 6-exo products 4b (29%) and 5a (35%),
respectively, along with traces of a bis-allylated benzene
byproduct11 (entry 4 of Table 1). In contrast, the reaction in
solution (MeCN) afforded the benzoxepine 4b (40%) as a major
product along with the benzopyran 5a (18%) (entry 5, Table
1). The 3,3-disubstituted methyl 4-bromo-2-methyl-2-butenoate
and 1-bromo-3-methyl-2-butene yielded the benzopyran 5b
(58%), along with a trace of an isomer arising from double-
bond migration,12 and the benzopyran 7 (56%), respectively
(entries 6 and 7, Table 1). The application of a stronger base
(e.g., t-BuOK vs Cs2CO3) increased the extent of the additional
elaboration of the aromatic ring, providing the benzopyrans 5c
(28%) and 5d (14%) instead of heterocycle 7 (compare entries
7 and 8 of Table 1). The benzopyrans 5 and 7 were isolated as
Figure 2. Proposed mechanism of the annulation reaction.
Scheme 2
1
single diastereomers. However, H NMR NOE experiments13
did not provide sufficient evidence for an unequivocal assign-
ment of the relative stereochemistry in heterocycles 5 and 7
(Table 1).
palladation)14 in the ortho position to afford the palladacycle
VIII, under conditions favoring the C(sp2)-H activation over
an intramolecular Heck reaction. The resulting palladacycle VIII
is poised for a second oxidative addition of allyl bromide,7
yielding Pd(IV) intermediate IX, which collapses to complex
X, providing the elaborated heterocycles 4 and 5 via 7-endo
and 6-exo Heck cyclizations, respectively.9 Substitution at the
adjacent carbons (1, 2, 3) in products 4 and 5 supports the
proposed ortho-metalation pathway, rather than an intermolecu-
lar electrophilic substitution on the corresponding 1,2-disubsti-
tuted heterocycles.14
Assuming the involvement of the Pd(IV) complex I, a
plausible mechanism for the formation of heterocycles 4 and 5
is shown in Figure 2. Intermediate VII arising from I would
undergo an intramolecular C(sp2)-H activation (electrophilic
(11) The 1,2-disubstituted benzene, the structure of which is shown
1
below, was isolated and identified by H and 13C NMR spectroscopy. Its
formation can be rationalized via C-allylation of the palladium ester enolate
VII (Figure 2) with the allyl bromide.
In a search for evidence for the proposed mechanistic
pathway, isolation of the reactive intermediates VII-X was
attempted. Low-temperature (0-8 °C) diffusion-controlled
crystallization (EtOAc/pentane) of the crude product from the
reaction between palladacycle 3a and neat methyl 4-bromo-2-
butenoate (45 °C, 30 min) afforded a single crystal, which was
shown by X-ray crystallographic analysis to represent the
proposed intermediate VII: e.g., the (o-allyl)arylpalladium(II)
bromo complex 10 (Scheme 2). The solid-phase structure of
complex 10 features an aromatic C-H bond (C6 in Figure 3)
in close proximity to the palladium(II) center. A similar
conformation of complex 10 in solution might contribute to the
apparently facile palladation of the ortho position in the aromatic
ring, leading to the proposed complex VIII (Figure 2). When
palladacycle 3a was allowed to react with neat methyl 4-bromo-
2-butenoate for an extended time (45 °C, 20 h), formation of
(12) The benzopyran with the structure shown below was isolated and
identified by 1H and 13C NMR spectroscopy. Its formation can be
rationalized by â-hydride elimination following migratory insertion from
intermediate X (Figure 2) occurring with the regiochemistry, giving rise to
a benzopyran with an exocyclic double bond, which isomerizes to the more
stable structure shown below.
(13) 1H NMR NOE experiments performed on benzopyrans 5a,b detected
the following correlations: (i) the methine proton bonded to carbon C2
showed an NOE correlation to a proton on the vinylic carbon directly bonded
to C3 (for 5a) or to a terminal proton in the vinyl side chain bonded to
carbon C3 (for 5b). However, inspection of the molecular models of different
conformations of benzopyrans 5a,b revealed that these correlations could
be present in both cis and trans heterocycles.
(14) Examples of palladation of aromatic rings directed by a heteroatom-
containing substituent in the ortho position are well-known; see: Dupont,
J.; Consorti, C. S.; Spencer, J. Chem. ReV. 2005, 105, 2527.

An Allylpalladium(IV) Intermediate
Organometallics, Vol. 26, No. 15, 2007 3877
Scheme 3
Figure 3. Thermal ellipsoid diagram of complex 10. The ellipsoids
are drawn at the 50% probability level.
Aiming to detect or isolate the presumed Pd(IV) intermediate
en route from palladacycle 3b to complex 11, we treated the
palladacycle 3b with neat methyl 4-bromo 2-butenoate at 0 °C
(8.5 h), during which time the cloudy solution turned clear.
Precipitation with pentane and solvent decantation performed
rapidly at -10 °C afforded a yellow solid, the 1H NMR
spectrum of which was recorded at -10 °C (see trace c in Figure
5). In addition to indicative signals for the remaining pallada-
cycle 3b (labeled # in traces a and c of Figure 5) and the
emerging “open form” complex 11 (labeled % in traces b and
c of Figure 5), as well as residual signals for allylic bromide
and/or alcohol16 (labeled × in trace c), signals (labeled V)
indicating the presence of a significant concentration16 of a
distinct palladium complex containing the allyl substituent (CH2-
CHdCHCO2Me) were detected (compare traces a-c of Figure
5). When it stood at room temperature, the CDCl3 solution of
the yellow solid (shown in trace c of Figure 5) was cleanly
Figure 4. Thermal ellipsoid diagram of complex 11. The ellipsoids
are drawn at the 50% probability level.
benzoxepine 4a was detected by GC analysis. However, due to
the labile nature of the reactive intermediates, no evidence for
the formation of a Pd(IV) intermediate en route from 3a to 10
could be obtained.
Reasoning that less sterically demanding and more rigid
bipyridine ligand will stabilize the reactive intermediates,
palladacycle 3b was prepared from aryl iodide 1 via complex
2b by an established method8 (Scheme 3). Indeed, the treatment
of palladacycle 3b with methyl 4-bromo-2-butenoate (2.0 equiv,
16 h, 80 °C) afforded the stable and robust arylpalladium(II)
bromo complex 11 (Scheme 3). Molecular structures of palla-
dacycle 3b and complex 11 were confirmed by X-ray crystal-
lographic analyses (Figure 4). The conversion of complex 11
into a benzoxepine via an intramolecular 7-endo-trig Heck
reaction9 required rather strenuous conditions, giving rise to
byproducts 13b and 13c. The addition of bases (DABCO) and
auxiliary phosphine ligands (PPh3) allowed for a successful
conversion of complex 11 into the single benzoxepine 13a
(MeCN, 100 °C, DABCO, PPh3)15 in good yield. Despite the
loss of the stereogenic center via double-bond isomerization,
the high-yielding formation of heterocycle 13a demonstrates
that complex 11 engages in reaction steps analogous to those
proposed for the more labile complex 10.
(15) The minor benzoxepine products 13b,c were isolated in variable
quantities, depending on the reaction conditions, and were identified by 1H
and 13C NMR spectroscopy. Heterocycle 13b may arise via Pd-mediated
decarboxylation following the formation of a benzoxepine substituted with
the Pd atom at C-3 via readdition of the H-Pd-X complex to the double
bond formed via â-hydride elimination. The heterocycle 13c could arise
via air oxidation of 13b.
(16) A partial hydrolysis of the excess allyl bromide during the washing
and decantation steps could account for the presence of the signal (singlet
at 4.93 ppm) in 1H NMR spectra in traces c and d. The ratios of Pd(IV)
complex 12, pallada(II)cycle 3b, and the “open form” complex 11 in the
yellow solid varied depending on the reaction conditions chosen. For
o
example, reaction for 5 min at 30 C afforded a mixture with a 12:3b:11
molar ratio of 3:4:1 (by 1H NMR). Under optimum conditions (8.5 h, 0
°C) the molar ratio 12:3b:11 was 10:2:1.

3878 Organometallics, Vol. 26, No. 15, 2007
Guo et al.
Figure 5. 1H NMR (400 MHz, CDCl3) of substrates and intermediates en route from 3b to 11.
converted to a solution of complex 11 (compare the spectral
traces b-d of Figure 5). The key 1H NMR signals (labeled V in
trace c of Figure 5) were assigned as follows: proton at 6.02
ppm (s, 1 H) as OCHa(COOEt)Pd; protons at 4.22 ppm (t, J )
7.2 Hz, 1 H) and 3.85 (ddd, J ) 15.6, 10.0, 6.8 Hz, 1 H) as the
two protons Hb and Hc in the allyl fragment -CHbHcCHd
CHCOOMe; protons at 3.15 ppm (dq, J ) 7.2, 3.2 Hz, 1 H)
and 2.82 (dq, J ) 7.2, 2.8 Hz, 1 H) as methylene protons Hf
and Hg in the ethyl ester group -C(dO)OCHfHgCH3, in the
structure of the Pd(IV) complex 12 (Scheme 3 and Figures 5
and 7)17 operating as an intermediate en route from palladacycle
3b to complex 11.
Encouraged by these results, we attempted the purification
and further characterization of complex 12. The yellow solid
obtained by the protocol described above was subjected to low-
temperature (-30 °C), diffusion-controlled crystallization (ethyl
acetate/pentane or ethyl acetate/hexane) to afford small and
twinned single crystals of a palladium complex,18 distinct from
the palladacycle 3b and the “open form” complex 11. Single-
domain crystals were obtained for two different solvent poly-
morphs. The asymmetric unit for one of these polymorphs
contains two crystallographically independent Pd(IV)-containing
molecules, and the asymmetric unit of the second polymorph
contains just one.18 Gratifyingly, the X-ray crystallographic
analysis unequivocally indicated that a cis isomer of the
Figure 6. Thermal ellipsoid diagram of the allylpalladium(IV)
complex 12. The ellipsoids are drawn at the 50% probability level.
Selected bond lengths (Å) and angles (deg): Pd(1)-C(2), 2.002-
(13); Pd(1)-C(7), 2.029(12); Pd(1)-C(11), 2.079(12); Pd(1)-N(1),
2.179(10); Pd(1)-N(2), 2.139(11); Pd(1)-Br(1), 2.606(2); C(2)-
Pd(1)-C(7), 78.6(6); C(2)-Pd(1)-Br(1), 97.1(4); C(2)-Pd(1)-
C(11), 88.4(5); C(11)-Pd(1)-N(2), 96.7(5); N(2)-Pd(1)-N(1),
75.7(4); N(1)-Pd(1)-C(2), 99.3(5).
(17) The assignments of protons in the structure of complex 12 as outlined
in Figures 5 and 7 are supported by 2D NMR experiments (COSY, HSQC)
recorded on the isolated complex 12. Thus, COSY spectroscopy revealed
correlations between (i) signals at 0.76 (t, J ) 6.8 Hz, 3 H, CH3), 3.15 (dq,
J ) 7.2, 3.2 Hz, 1 Hf), and 2.82 ppm (dq, J ) 7.2, 2.8 Hz, 1 Hg) and (ii)
signals at 7.36 (dt, J ) 15.2, 9.0 Hz, 1 Hd), 4.22 (t, J ) 7.2 Hz, 1 Hb), and
3.85 ppm (ddd, J ) 15.6, 10.0, 6.8 Hz, 1 Hc). HSQC spectroscopy revealed
correlations between (i) signals at 3.15 (Hf) and 2.82 ppm (Hg) and a single
carbon at 59.8 ppm and (ii) signals at 4.22 (Hb) and 3.85 ppm (Hc) and a
single carbon at 38.1 ppm.
(18) Although repeated attempts to grow larger high-quality single
crystals of 12 were unsuccessful, the acquired small ((0.12-0.19) × (0.08-
0.010) × 0.03 mm3) single-domain crystals obtained for the two different
solvent polymorphs gave acceptable yields of data to 2θ(Mo KR) ) 45.0°.
Even though the lower yield of data for both polymorphs necessarily reduces
the precision of the resulting structural parameters, all three molecules have
the same Pd stereochemistry and consistent Pd-ligand bond lengths.
proposed allylpalladium(IV) intermediate 12 was indeed formed
(Scheme 3 and Figure 6).18 All three molecules of 12 possess
a distorted-octahedral geometry with the phenyl-o-(ethoxycar-
bonylmethyleneoxo) groups forming a five-membered chelate
ring that contains the palladium and two (sp3-hybridized carbon
atom C7 and sp2-hybridized carbon atom C(2)) of the three
carbon atoms bonded to it. The five non-hydrogen atoms
comprising this chelate ring in each of these three molecules
are slightly noncoplanar (rms deviations from the respective
least-squares mean planes range from 0.07 to 0.14 Å). The sp3-
hybridized carbon atom C7 deviates the most from each mean

An Allylpalladium(IV) Intermediate
Organometallics, Vol. 26, No. 15, 2007 3879
Figure 7. 1H NMR spectra recorded for the crystallized complex 12 (400 MHz, CDCl3, -10 °C).
plane (ranging from 0.11 to 0.23 Å) in one direction, and the
oxygen atom has the next largest deviation (ranging from 0.10
to 0.19 Å), but in the opposite direction from the least-squares
mean plane. The allyl substituent in complex 12 resides cis to
the bromide ligand and cis to the aromatic carbon (C2) of the
chelate ring. Both the allyl group and the coordinated aromatic
carbon (C2) are positioned trans to the nitrogen atoms of the
bipyridine ligand. The Pd-N, Pd-Br, and Pd-CH2(allyl) bond
lengths are in agreement with those found in related com-
plexes,19 and the Pd-C(sp2) (aryl) and Pd-C(sp3) (methylene)
bond lengths Pd-C2 and Pd-C7, respectively, as well as the
Pd-N bond lengths, are comparable to those found for the
analogous square-planar pallada(II)cycle 3b.19
The preferential formation of the cis isomer of complex 12
is in agreement with the cis structure assigned for a related
benzylpallada(IV)cyclic complex by Catelani on the basis of
NMR spectroscopic studies6 but is in contrast with the genera-
tion of cis/trans isomer mixtures detected by NMR in reactions
of palladacyclopentane with [Ph2I][OTf].4d 1H NMR spectra
recorded on CDCl3 solutions of the single crystals of complex
12 at low temperatures (-10 °C) (Figure 7) showed signals
identical with those highlighted in trace c of Figure 5 and
revealed that no isomerization of complex 12 occurred for 5 h
at subzero temperatures in the CDCl3 solution. Rather, a slow
conversion of complex 12 into complex 11 was detected to occur
even at subzero temperatures. In the spectrum of pure crystal-
lized complex 12 (Figure 7) further assignments of the indicative
1H NMR signals could be made for protons Hd (7.36 ppm (dt,
J ) 15.2, 9.0 Hz, 1 Hd)) and He (6.00 ppm (d, J ) 15.2 Hz))
in the allyl fragment (-CH2CHddCHeCOOMe).17 The palla-
dium(IV) complex 12 was sufficiently stable in solution to
permit the collection of 13C NMR data (CDCl3, -10 °C), and
the solid complex 12 could be handled at room temperature for
short time periods, although prolonged standing of solid 12 at
room temperature resulted in its conversion to complex 11.20
Conclusions
In conclusion, a formal annulation between two electrophiles
was studied in a stoichiometric mode exploiting the reactivity
of stable pallada(II)cycles bearing bis(imine) or bipyridine
ligands with allyl bromides. Highly substituted benzoxepines
and benzopyrans featuring three new C-C bonds and up to two
stereogenic centers were obtained in good yields via a multistep
cascade sequence involving functionalization of a C(sp2)-H
bond. Studies of this transformation with a palladacycle bearing
a rigid bipyridine ligand led to isolation of the rare reactive
allylpalladium(IV) complex 12, which was characterized by low-
1
temperature H and 13C NMR analyses as well as by X-ray
crystallography and could be converted into the stable palla-
dium(II) complex 11 and subsequently into a benzoxepine
heterocycle. Isolation of reactive palladium(IV) complexes that
can give rise to complex organic products remains rare, and
the present study demonstrates the potential of the protocols
involving Pd(0)-Pd(II)-Pd(IV) interconversions for the gen-
eration of complex heterocyclic products.
Experimental Section
(19) Data published in ref 4m for complex Me3PdIV(bipyridine)I indicate
Pd-C(a-c) ) 2.046, 2.034, and 2.040 Å, Pd-N(a,b) ) 2.188 and 2.173
Å, and Pd-I ) 2.834 Å. X-ray crystallographic analyses on pallada(II)-
cycles 3a,b (see the Supporting information) indicated the following.
Complex 3a: Pd-C(sp2) ) 2.013 Å, Pd-C(sp3) ) 2.026 Å, Pd-N(1,2) )
2.162, 2.123 Å. Complex 3b: Pd-C(sp2) ) 1.991 Å, Pd-C(sp3) ) 2.043
Å, Pd-N(1,2) ) 2.114, 2.126 Å.
General Method for the Synthesis of Arylpalladium(II) Iodo
Complexes 2a,b. To a solution of tris(dibenzylideneacetone)-
dipalladium(0) (Pd2(dba)3; 1.0 mmol) in benzene (30-45 mL) at
room temperature under argon was added the appropriate ligand
(20) The half-life is approximately 3 h.

3880 Organometallics, Vol. 26, No. 15, 2007
Guo et al.
(3-4 mmol) followed by a solution of 2-{[(ethoxycarbonyl)-
methylene]oxy}-1-iodobenzene (1; 2.2 mmol) in benzene (10 mL).
The reaction mixture was warmed to the indicated temperature,
stirred for the indicated time period, and filtered through a plug of
Celite, and solvents were removed under reduced pressure to afford
a crude product. The crude product was purified by flash chroma-
tography over silica, with EtOAc/hexane (1:5) as eluent to remove
dibenzylideneacetone (dba) and subsequently with EtOAc/hexane
(1:1) to afford arylpalladium(II) complexes 2a,b as bright yellow
solids.
crystallographic analysis (see data in the Supporting Information):
mp 152-155 °C (CDCl3, decomp); Rf ) 0.29 (EtOAc/hexane 1:1);
1H NMR (500 MHz, CDCl3) δ 8.09 (s, 1 H), 8.05 (s, 1 H), 7.13 (d,
J ) 7.5, 1 H), 6.98 (t, J ) 7.6 Hz, 1 H), 6.77 (d, J ) 7.9 Hz, 1 H),
6.67 (t, J ) 7.4 Hz, 1 H), 6.03 (s, 1 H), 4.56 (t br, J ) 9.5 Hz,
1 H), 4.17 (t br, J ) 9.5 Hz, 1 H), 4.08 (q, J ) 7.1 Hz, 2 H), 2.67
(d, J ) 9.2 Hz, 1 H), 2.39 (d, J ) 7.2 Hz, 1 H), 2.24 (d, J )
10.0 Hz, 1 H), 2.00-1.70 (m br, 8 H), 1.55-1.45 (m, 5 H), 1.32-
1.16 (m, 4 H), 1.14 (t, J ) 7.0 Hz, 3 H); 13C NMR (125 MHz,
CDCl3) δ 177.1, 174.6, 157.9, 157.4, 137.5, 133.8, 126.4, 117.8,
108.6, 87.4, 65.11, 64.7, 59.5, 36.1, 33.6, 33.5, 31.5, 25.8, 25.6,
25.6, 25.5, 25.4, 25.3, 14.4; IR (KBr, cm-1) 2929 (s), 1697 (s),
1166 (s); HRMS (ES+) calcd for C24H35N2O3Pd (M + H+) m/z
505.1682, found m/z 505.1685.
{2-[(Ethoxycarbonyl)methoxy]phenyl}iodo(N,N′-bis(cyclo-
hexyl)ethylenediimine)palladium (2a). The treatment of Pd2(dba)3
(1.832 g, 2.0 mmol), N,N′-bis(cyclohexyl)ethylenediimine
(1.320 g, 6.0 mmol), and 2-{[(ethoxycarbonyl)methylene]oxy}-1-
iodobenzene (1; 1.346 g, 4.4 mmol) for 2 h at room temperature
according to the method described above afforded the arylpalla-
dium(II) iodo complex 2a as a bright yellow solid (1.845 g, 73%):
mp 126-128 °C (EtOAc/hexane 1:1); Rf ) 0.43 (EtOAc/hexane
{[(Ethoxycarbonyl)methineoxy]-1,2-phenylene}[N,N′-2,2′-
dipyridyl]palladium (3b). Treatment of palladium complex 2b
(1.721 g, 3.0 mmol) and a 1 M solution of t-BuOK in THF
(3.6 mL, 3.6 mmol) as described above, followed by removal of
the solvents under reduced pressure, addition of CH2Cl2 (20 mL),
filtration through Celite and a small plug of basic alumina with
methylene chloride as eluent, final removal of solvents under
reduced pressure, and trituration with ethyl ether, afforded palla-
dacycle 3b (1.177 g, 88%). A single crystal for X-ray crystal-
lographic analysis was prepared by diffusion-controlled crystalli-
zation from an EtOAc/hexane mixture: mp 192-195 °C (EtOAc/
hexane); Rf ) 0.38 (EtOAc/CH2Cl2 2:1); 1H NMR (500 MHz,
CDCl3) δ 9.38 (d, J ) 4.8 Hz, 1 H), 9.20 (d, J ) 5.2 Hz, 1 H),
8.09 (t, J ) 6.8 Hz, 2 H), 8.04 (td, J ) 7.6, 1.6 Hz, 1 H), 8.00 (td,
J ) 7.6, 1.2 Hz, 1 H), 7.61 (t, J ) 6.8 Hz, 1 H), 7.56 (t, J )
6.8 Hz, 1 H), 7.25 (d, J ) 7.6 Hz, 1 H), 7.04 (t, J ) 8.0 Hz, 1 H),
6.82 (dd, J ) 8.0, 0.8 Hz, 1 H), 6.77 (t, J ) 7.6 Hz, 1 H), 6.31 (s,
1 H), 4.18-4.02 (m, 2 H), 1.13 (t, J ) 7.0 Hz, 3 H); 13C NMR
(125 MHz, CDCl3) δ 178.1, 174.5, 155.4, 154.4, 152.3, 150.8,
139.6, 138.6, 138.3, 133.7, 126.0, 125.9, 125.8, 122.1, 121.5, 118.2,
108.5, 87.9, 59.6, 14.2; IR (KBr, cm-1) 1697 (s), 1441 (s), 1168
(s), 756 (s); HRMS (ES+) calcd for C20H19O3N2Pd (M + H+) m/z
441.0430, found m/z 441.0442.
1
1:1); H NMR (400 MHz, CDCl3) δ 7.99 (s, 1 H), 7.96 (s, 1 H),
7.33 (d, J ) 7.6 Hz, 1 H), 6.86 (t, J ) 7.2 Hz, 1 H), 6.71 (t, J )
7.2 Hz, 1 H), 6.52 (d, J ) 8.0 Hz, 1 H), 4.93 (d, J ) 16.8 Hz,
1 H), 4.62 (d, J ) 16.8 Hz, 1 H), 4.41 (t, J ) 7.2 Hz, 1 H), 4.22-
4.17 (m, 2 H), 3.11 (t, J ) 7.2 Hz, 1 H), 2.24 (d, J ) 11.2 Hz,
2 H), 2.02-1.83 (m, 4 H), 1.72 (t, J ) 6.8 Hz, 2 H), 1.65-1.38
(m, 4 H), 1.29 (t, J ) 6.8 Hz, 3 H), 1.29-1.13 (m, 4 H), 1.05-
0.75 (m, 3 H), 0.75-0.55 (m, 1 H); 13C NMR (125 MHz, CDCl3)
δ 170.3, 160.2, 158.8, 157.0, 138.8, 130.3, 124.3, 121.3, 114.2,
67.2, 66.1, 65.4, 60.7, 34.5, 33.4, 33.3, 32.2, 25.6, 25.5, 25.4, 25.3,
25.1, 25.0, 14.3; IR (KBr, cm-1) 2929 (s), 1757 (s), 1448 (s), 1186
(s); HRMS (ES+) calcd M - I C24H35N2O3Pd m/z 505.1682, found
m/z 505.1675.
{2-[(Ethoxycarbonyl)methoxy]phenyl}iodo(N,N′-2,2′-dipyridyl)-
palladium (2b). The treatment of Pd2(dba)3 (2.003 g, 2.18 mmol).
2,2′-dipyridyl (1.367 g, 8.75 mmol), and 2-{[(ethoxycarbonyl)-
methylene]oxy}-1-iodobenzene (1a; 1.475 g, 4.817 mmol) for
1.6 h at 55 °C (oil bath) according to the method described above
afforded the arylpalladium(II) iodo complex 2b as a bright yellow
solid (1.738 g, 70%): mp 195-198 °C (EtOAc/hexane 1:1); Rf )
0.59 (EtOAc/CH2Cl2 1:1); 1H NMR (400 MHz, CDCl3) δ 9.61 (dd,
J ) 5.2, 0.8 Hz, 1 H), 8.14 (t, J ) 8.0 Hz, 2 H), 8.02 (td, J ) 7.6,
1.6 Hz, 1 H), 7.96 (td, J ) 7.6, 1.6 Hz, 1 H), 7.77 (dd, J ) 5.2,
0.8 Hz, 1 H), 7.48 (m, 2 H), 7.30 (t, J ) 6.8 Hz, 1 H), 6.98 (t, J
) 8.8 Hz, 1 H), 6.82 (td, J ) 7.2, 1.2 Hz, 1 H), 6.64 (dd, J ) 8.0,
1.2 Hz, 1 H), 4.95 (d, J ) 16.4 Hz, 1 H), 4.72 (d, J ) 16.8 Hz,
1 H), 4.16 (dq, J ) 7.2, 3.6 Hz, 2 H), 1.23 (t, J ) 7.2 Hz, 3 H);
13C NMR (100 MHz, CDCl3) δ 170.3, 160.2, 155.6, 154.0, 153.0,
151.0, 138.8, 138.7, 138.5, 132.1, 126.6, 126.4, 124.6, 122.1, 121.8,
121.5, 114.0, 67.0, 60.7, 14.2; IR (KBr, cm-1) 1748 (s), 1442 (s),
1187 (s), 759 (s); HRMS (ES+) calcd for C20H19O3PdN2 (M - I)
m/z 441.0430, found m/z 441.0436.
{1-(Ethoxycarbonyl)-1-{2-(3-(methoxycarbonyl)-2-propenyl)-
phenoxy]methyl}bromo[N,N′-bis(cyclohexyl)ethylenediimine]-
palladium (10). A suspension of pallada(II)cycle 3a (0.020 g, 0.040
mmol) in methyl trans-4-bromo-2-butenoate (0.20 mL, 1.67 mmol)
was stirred for 20 min at 45 °C until a clear solution was formed.
The reaction mixture was stirred for an additional 10 min and cooled
to room temperature, and pentane (3 mL) was added. The liquid
was decanted, and the remaining yellow solid was washed with
pentane (2 × 3 mL) to afford complex 10 free of unreacted
1
palladacycle 3a (by H NMR) as a yellow solid (0.026 g, 95%),
which decomposed upon standing for several hours in CDCl3
solution at room temperature under argon. A diffusion-controlled
crystallization from EtOAc/pentane (3 days, 0 -5 °C) afforded a
single crystal that was used for X-ray crystallographic analysis (data
provided in the Supporting Information): mp 138-140 °C dec
General Procedure for the Synthesis of Pallada(II)cycles 3a,b.
To a solution of the arylpalladium(II) iodo complex (1.0 mmol) in
THF (22-40 mL) was injected simultaneously a 1 M solution of
t-BuOK in THF (1.1-1.2 mmol). The resulting suspension was
stirred for 5-15 min at room temperature under argon. Following
a workup protocol specific for each pallada(II)cycle, palladacycles
3a,b were obtained as yellow solids.
1
(EtOAc/pentane), Rf ) 0.35 (EtOAc/hexanes 1:1); H NMR (500
MHz, CDCl3) δ 7.96 (d, J ) 8.0 Hz, 1 H), 7.93 (s, 1 H), 7.79 (s,
1 H), 7.18 (t, J ) 8.0 Hz, 1 H), 7.02 (dt, J ) 15.5, 6.5 Hz, 1 H),
6.96 (d, J ) 7.5 Hz, 1 H), 6.83 (t, J ) 7.5 Hz, 1 H), 6.28 (s, 1 H),
5.79 (dd, J ) 15.5, 0.5 Hz, 1 H), 4.56 (t, J ) 11.5 Hz, 1 H), 4.31
(t, J ) 11.5 Hz, 1 H), 4.15 (q, J ) 7.0 Hz, 2 H), 3.61 (s, 3 H),
3.62-3.60 (m, 1 H), 3.47 (dd, J ) 16.5, 6.5 Hz, 1 H), 2.20 (d, J
) 11.5 Hz, 1 H), 2.03 (s br, 2 H), 1.82-1.64 (m, 9 H), 1.50-1.00
(m, 8 H), 1.25 (t, J ) 7.0 Hz, 3 H); 13C NMR (125 MHz, CDCl3)
δ 173.5, 167.0, 161.7, 156.9, 156.0, 147.6, 129.5, 128.3, 126.5,
121.8, 121.0, 115.3, 65.0, 64.4, 60.3, 60.1, 51.3, 35.9, 33.6, 33.5,
32.9, 32.6, 25.5 (2 carbons), 25.4, 25.2, 25.16, 25.1, 14.5; IR (KBr,
cm-1) 1714 (s), 1652 (s); HRMS (ES+) calcd for C29H41N2O5Pd
(M+ - Br) m/z 603.2050, found m/z 603.2053.
{[(Ethoxycarbonyl)methineoxy]-1,2-phenylene}[N,N′-bis(cy-
clohexyl)ethylenediimine]palladium (3a). Treatment of the pal-
ladium complex 2a (0.632 g, 1.0 mmol) and a 1 M solution of
t-BuOK in THF (1.1 mL, 1.1 mmol) as described above, followed
by filtration through Celite and a small plug of basic alumina with
methylene chloride as eluent, removal of solvents under reduced
pressure, and trituration of the crude product with a hexane and
ethyl acetate mixture, afforded palladacycle 3a (0.370 g, 73%) as
a yellow powder. Slow crystallization from a solution in CDCl3
(0-10 °C) afforded a single crystal of 3a suitable for X-ray

An Allylpalladium(IV) Intermediate
Organometallics, Vol. 26, No. 15, 2007 3881
{1-(Ethoxycarbonyl)-1-[2-(3-(methoxycarbonyl)-2-propenyl)-
phenoxy]methyl}bromo(N,N′-2,2′-dipyridyl)palladium (11). To
a solution of the pallada(II)cycle 3b (1.149 g, 2.608 mmol) in 1,2-
dichloroethane (36 mL) was added methyl trans-4-bromo-2-
butenoate (0.62 mL, 5.188 mmol). The reaction mixture was heated
to 80 °C and stirred for 16 h. The solvent was partially removed
under reduced pressure to afford a yellow powder, which was
collected by filtration and washed with ethyl ether to afford complex
11 as a light yellow solid (1.478 g, 91%). Diffusion-controlled
crystallization (EtOAc/pentane) at room temperature (3 days)
afforded a single crystal of complex 11, which was used for X-ray
crystallographic analysis (data provided in the Supporting Informa-
tion): mp 172-174 °C (EtOAc/pentane); Rf ) 0.44 (EtOAc/CH2-
Cl2 2:1); 1H NMR (400 MHz, CDCl3) δ 9.87 (d, J ) 5.2 Hz, 1 H),
9.59 (d, J ) 5.6 Hz, 1 H), 8.22 (d, J ) 8.0 Hz, 1 H), 8.00-7.97
(m, 4 H), 7.61 (dt, J ) 6.8, 2.4 Hz, 1 H), 7.51 (q, J ) 4.8 Hz, 1
H), 7.30 (t, J ) 8.4 Hz, 1 H), 7.13 (dt, J ) 15.6, 6.4 Hz, 1 H), 7.03
(dd, J ) 7.2, 0.8 Hz, 1 H), 6.91 (td, J ) 7.2, 0.8 Hz, 1 H), 6.68 (s,
1 H), 5.77 (d, J ) 15.6 Hz, 1 H), 4.33 (dq, J ) 7.2, 10.2 Hz, 1 H),
4.18 (dq, J ) 7.2, 10.2 Hz, 1 H), 3.74 (dd, J ) 16.0, 6.4 Hz, 1 H),
3.73 (s, 3 H), 3.57 (dd, J ) 16.0, 6.4 Hz, 1 H), 1.33 (t, J ) 7.0 Hz,
3 H); 13C NMR (100 MHz, CDCl3) δ 174.3, 167.0, 155.5, 155.2,
153.6, 153.4, 151.6, 148.0, 138.9, 138.6, 129.8, 128.5, 126.9, 126.3,
125.9, 121.6, 121.5, 121.2, 120.9, 114.9, 60.2, 58.4, 51.3, 32.8,
14.4; IR (KBr, cm-1) 1724 (s), 1701 (s), 1488 (s), 1444 (s), 1193
(s), 1035 (s), 765 (s); HRMS (ES+) calcd for C25H25N2O5Pd (M+
- Br) m/z 539.0798, found m/z 539.0817.
of the complex at room temperature precluded the collection of
melting point, HRMS, and IR data.
2-(Ethoxycarbonyl)-3-(methoxycarbonyl)-9-[3-(methoxycar-
bonyl)-2-trans-propenyl]-2,5-dihydro-1-benzoxepine (4a). Entry
1 (Table 1). To a solution of the pallada(II)cycle 3a (0.025 g, 0.050
mmol) in 1,2-dichloroethane (0.5 mL) in a pressure tube equipped
with a magnetic stirring bar was added neat methyl trans-4-
bromobutenoate (0.036 mL, 0.300 mmol) and solid freshly sublimed
t-BuOK (0.020 g, 0.178 mmol). The tube was purged with argon
and capped, and the contents were stirred for 20 h at 95 °C (oil
bath). The reaction mixture was cooled, diluted with methylene
chloride, and filtered though a short plug of Celite, and solvents
were removed under reduced pressure to afford the crude product,
which was separated by flash chromatography over silica with
EtOAc/hexane (1:9) as eluent to afford the benzoxepine 4a
(0.010 g, 53%) as a light yellow oil.
Entry 2 (Table 1). To a suspension of the pallada(II)cycle 3a
(0.050 g, 0.100 mmol) in neat methyl trans-4-bromobutenoate
(0.20 mL, 1.674 mmol) in a pressure tube equipped with a magnetic
stirring bar was added NaBr (0.021 g, 0.200 mmol). The reaction
(1.5 h at 85 °C) and the workup were performed as described above
to afford benzoxepine 4a (0.019 g, 50%) as a light yellow oil and
phenol 6 (0.003 g, 15%) as a colorless oil.
Entry 3 (Table 1). To a suspension of the pallada(II)cycle 3a
(0.050 g, 0.100 mmol) in neat methyl trans-4-bromobutenoate (0.20
mL, 1.674 mmol) in a pressure tube equipped with a magnetic
stirring bar was added Cs2CO3 (0.090 g, 0.277 mmol). The reaction
(2 h at 95 °C) and the workup were performed as described above
to afford the benzoxepine 4a (0.023 g, 62%) as a light yellow oil.
Analytical data for benzoxepine 4a are as follows: Rf ) 0.33
(EtOAc/hexane 1:5); 1H NMR (500 MHz, CDCl3) δ 7.15 (dt, J )
15.5, 7.0 Hz, 1 H), 6.96 (d, J ) 7.5 Hz, 1 H), 6.87 (d, J ) 6.5 Hz,
1 H), 6.82 (t, J ) 7.5 Hz, 1 H), 6.41 (s, 1 H), 5.83 (d, J ) 15.5 Hz,
1 H), 5.43 (s, 1 H), 4.13 (q, J ) 7.0 Hz, 2 H), 3.74 (s, 3 H), 3.70
(s, 3 H), 3.59 (dd, J ) 15.7, 6.8 Hz, 1 H), 3.52 (dd, J ) 16.0, 6.5
Hz, 1 H), 3.45 (d, J ) 16 Hz, 1 H), 3.29 (d, J ) 16.5 Hz, 1 H),
1.19 (t, J ) 7.0 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 170.6,
169.2, 167.1, 149.8, 147.3, 130.5, 125.5, 125.3, 124.9, 124.6, 121.6
(two carbons), 120.9, 74.9, 61.5, 52.2, 51.4, 38.9, 32.3, 14.0; IR
(neat, cm-1) 1732 (s), 1275 (s), 1192 (s); HRMS (ES+) calcd for
C20H22O7K (M + K+) m/z 413.1003, found m/z 413.0983.
cis-[(Ethoxycarbonyl)methineoxy-1,2-phenylene][N,N′-2,2′-
dipyridyl][3-(methoxycarbonyl)-2-propenyl]bromopalladium (12).
The pallada(II)cycle 3b (0.020 g, 0.0455 mmol) was treated with
neat methyl trans-4-bromobutenoate (0.400 mL, 3.34 mmol) at 0
°C for 8.5 h, during which time the yellow solid of palladacycle
3b gradually dissolved, forming a clear yellow solution. Cold
pentane (5.0 mL, -10 °C) was added, and the resulting light yellow
precipitate was separated by decantation, washed with cold pentane
1
(3 × 5 mL, -10 °C), and dried in vacuo at -10 °C. H NMR
analysis on the solid indicated that it consisted of a mixture of the
pallada(II)cycle 3b, the arylpalladium(II)bromo complex 11, and
a new complex, e.g., the pallada(IV)cycle 12 in the molar ratio
12:3b:11 ) 10:2:1, as well as some remaining allyl bromide and
the corresponding allylic alcohol (see trace c in Figure 5). A portion
(0.005 g) of the yellow solid prepared by this method was dissolved
in cold ethyl acetate (-20 °C, 1.6 mL) and the solution was layered
with cold pentane or hexane (5.0 mL) to establish diffusion-
controlled crystallization conditions. On standing at -20 °C for 3
days, small light yellow crystals of pallada(IV)cycle 12 were
formed, collected, and fully characterized (1H NMR, 13C NMR,
COSY, HSQC recorded at -10 °C), including a single-crystal X-ray
crystallographic analysis (data provided in the Supporting Informa-
tion). In solution (CDCl3) complex 12 underwent a slow conversion
into the arylpalladium(II) bromide complex 11 both at -20 °C and
at room temperature (over 16 h periods). The solid complex 12
has limited thermal stability at room temperature and undergoes a
slow conversion into complex 11 (half-life approximately 3 h).
Analytical data for the phenol 6 are as follows: Rf ) 0.34
1
(hexane/EtOAc 5:1); H NMR (500 MHz, CDCl3) δ 7.20-7.13
(m, 2 H), 7.11 (d, J ) 7.5 Hz, 1 H), 6.91 (t, J ) 7.5 Hz, 1 H), 6.78
(d, J ) 8.0 Hz, 1 H), 5.83 (td, J ) 16.0 Hz, 1.8 Hz, 1 H), 4.96 (s,
1 H), 3.73 (s, 3 H) 3.55 (dd, J ) 6.5 Hz, 1.5 Hz, 2 H); 13C NMR
(125 MHz, CDCl3) δ 167.1, 153.5, 147.1, 130.7, 128.2, 124.1,
121.7, 121.1, 115.5, 51.5, 32.9; IR (neat, cm-1) 3250 (w br), 1720
(s), 1456 (m), 1274 (m); HRMS (ES+) calcd for C11H13O3 (M +
H+) m/z 193.0865, found m/z 193.0861.
2-(Ethoxycarbonyl)-3-methyl-9-(trans-2-butenyl)-2,5-dihydro-
1-benzoxepine (4b) and 2-(Ethoxycarbonyl)-3-ethenyl-8-(trans-
2-butenyl)-3,4-dihydro-2H-1-benzopyran (5a). Entry 4 (Table
1). To a suspension of the pallada(II)cycle 3a (0.051 g, 0.100 mmol)
in neat crotyl bromide (0.60 mL, 5.830 mmol) in a pressure tube
equipped with a magnetic stirring bar was added Cs2CO3 (0.081 g,
0.250 mmol). The tube was purged with argon and capped, and
the contents were stirred for 2 h at 115 °C (oil bath). The reaction
mixture was cooled, diluted with methylene chloride, and filtered
though a short plug of Celite. Solvents were removed under reduced
pressure to afford a crude product, which was separated by flash
chromatography over silica with methylene chloride/hexane (1:1)
as eluent to afford benzoxepine 4b (0.083 g, 29%) and benzopyran
5a (0.010 g, 35%) as colorless oils.
Analytical data for complex 12 are as follows: 1H NMR (400
MHz, CDCl3, -10 °C) δ 8.88 (d, J ) 4.8 Hz, 1 H), 8.29 (d, J )
8.0 Hz, 1 H), 8.25-8.14 (m, 3 H), 8.11 (d, J ) 7.6 Hz, 1 H), 8.04
(t, J ) 7.8 Hz, 1 H), 7.74 (t, J ) 6.4 Hz, 1 H), 7.46 (t, J ) 6.4 Hz,
1 H), 7.36 (dt, J ) 15.2, 9.0 Hz, 1 H), 7.12 (t, J ) 7.6 Hz, 1 H),
6.90 (t, J ) 9.0 Hz, 2 H), 6.02 (s, 1 H), 6.00 (d, J ) 15.2 Hz, 1 H),
4.22 (t, J ) 7.2 Hz, 1 H), 3.85 (ddd, J ) 15.6, 10.0, 6.8 Hz, 1 H),
3.66 (s, 3 H), 3.15 (dq, J ) 7.2, 3.2 Hz, 1 H), 2.82 (dq, J ) 7.2,
2.8 Hz, 1 H), 0.76 (t, J ) 6.8 Hz, 3 H); 13C NMR (CDCl3, 100
MHz, -10 °C) δ 170.9, 167.2, 153.8, 153.6, 153.3, 150.2, 148.8,
147.9, 139.5, 139.2, 135.0, 127.4, 126.3, 126.2, 123.2, 122.3, 122.1,
121.3, 118.8, 111.4, 95.9, 59.8, 51.4, 38.1, 13.5. The limited stability
Entry 5 (Table 1). To a solution of the pallada(II)cycle 3a (0.051
g, 0.100 mmol) in acetonitrile (0.8 mL) in a pressure tube equipped
with a magnetic stirring bar was added neat crotyl bromide

3882 Organometallics, Vol. 26, No. 15, 2007
Guo et al.
(0.100 mL, 1.00 mmol) and solid Cs2CO3 (0.081 g, 0.250 mmol).
The reaction (60 h at 115 °C) and the workup were performed as
described above (for entry 4) to afford the benzoxepine 4b
(0.012 g, 40%) and the benzopyran 5a (0.005 g, 18%), both as
colorless oils.
7.03 (d, J ) 7.0 Hz, 1 H), 6.89 (d, J ) 8.5 Hz, 1 H), 6.87 (t, J )
7.5 Hz, 1 H), 4.89 (t, J ) 1.5 Hz, 1 H), 4.85 (s, 1 H), 4.64 (d, J )
7.5 Hz, 1 H), 4.23 (q, J ) 7.5 Hz, 2 H), 2.89-2.81 (m, 3 H), 1.82
(s, 3 H), 1.27 (t, J ) 7.5 Hz, 3 H); 13C NMR (125 MHz, CDCl3)
δ 170.0, 152.8, 143.3, 129.2 (CH), 127.5 (CH), 120.9 (CH), 120.7,
116.5 (CH), 113.7 (CH2), 76.9 (CH), 61.2 (CH2), 41.9 (CH), 28.5
(CH2), 20.2 (CH3), 14.1 (CH3); IR (neat, cm-1) 1753 (s br), 1488
(m), 1197 (m); HRMS (ES+) calcd for C15H19O3 (M + H+) m/z
247.1334, found m/z 247.1330.
2-(Ethoxycarbonyl)-3-(1-methyl-1-ethenyl)-8-(3-methyl-2-buten-
1-yl)-3,4-dihydro-2H-1-benzopyran (5c) and 2-(Ethoxycarbo-
nyl)-3-isopropyl-8-(3-methyl-2-buten-1-yl)-2H-1-benzopyran (5d).
Entry 8 (Table 1). To a solution of the pallada(II)cycle 3a (0.051
g, 0.100 mmol) in 1,2-dichloroethane (1.0 mL) in a pressure tube
equipped with a magnetic stirring bar was added 1-bromo-3-methyl-
2-butene (0.070 mL, 0.60 mmol) and freshly sublimed t-BuOK
(0.046 g, 0.410 mmol). The tube was purged with argon and capped,
and the contents were stirred for 2 h at 115 °C (oil bath). The
reaction mixture was cooled, diluted with methylene chloride, and
filtered though a short plug of Celite, and solvents were removed
under reduced pressure to afford a crude product, which was
separated by flash chromatography over silica with methylene
chloride/hexane (1:5) as eluent to afford benzopyrans 5c (0.009 g,
28%) and 5d (0.004 g, 14%), both as colorless oils.
Analytical data for benzoxepine 4b are as follows: Rf ) 0.60
(EtOAc/hexane 1:5); 1H NMR (500 MHz, CDCl3) δ 6.99 (dd, J )
6.5, 2.5 Hz, 1 H), 6.86-6.80 (m, 2 H), 6.26 (s, 1 H), 5.65 (pent q,
J ) 7.5, 1.5 Hz, 1 H), 5.35 (pent t, J ) 7.0, 1.0 Hz, 1 H), 5.21 (s,
1 H), 4.20-4.10 (m, 2 H), 3.49-3.28 (m, 2 H), 2.42 (sext, J ) 7.5
Hz, 1 H), 2.27 (sext, J ) 8.0 Hz, 1 H), 1.69 (dq, J ) 6.0, 1.5 Hz,
3 H), 1.22 (s, 3 H), 1.20 (t, J ) 7.5 Hz, 3 H); 13C NMR (125 MHz,
CDCl3) δ 169.7, 149.5, 133.7 (two carbons), 129.3, 129.2, 127.9,
125.9, 124.2, 121.2, 119.4, 76.1, 61.2, 32.4, 26.1, 17.9, 14.1, 11.4;
IR (neat, cm-1) 1751 (s), 1731 (s), 1456 (s); HRMS (ES+) calcd
for C18H23O3 (M + H+) m/z 287.1647, found m/z 287.1650.
Analytical data for benzopyran 5a are as follows: Rf ) 0.59
1
(EtOAc/hexane 1:5); H NMR (400 MHz, CDCl3) δ 7.00 (d, J )
6.0 Hz, 1 H), 6.93 (d, J ) 7.6 Hz, 1 H), 6.83 (t, J ) 7.6 Hz, 1 H),
5.83 (ddd, J ) 16.8, 10.4, 8.0 Hz, 1 H), 5.69-5.58 (m, 1 H), 5.56-
5.48 (m, 1 H), 5.24 (dt, J ) 16.8, 1.2 Hz, 1 H), 5.16 (dd, J ) 10.4,
0.8 Hz, 1 H), 4.57 (d, J ) 6.8 Hz, 1 H), 4.24 (qd, J ) 7.2, 2.8 Hz,
2 H), 3.45-3.25 (m, 2 H), 2.97 (dt, J ) 13.2, 7.2 Hz, 1 H), 2.89
(dd, J ) 16.0, 5.2 Hz, 1 H), 2.74 (dd, J ) 16.4, 7.6 Hz, 1 H), 1.69
(dd, J ) 6.0, 1.6 Hz, 3 H), 1.29 (t, J ) 7.2 Hz, 3 H); 13C NMR
(100 MHz, CDCl3) δ 170.3, 150.6, 136.8, 129.3, 128.7, 127.7,
127.3, 125.9, 120.5, 119.8, 117.2, 77.7, 61.2, 38.7, 32.8, 29.3, 17.9,
14.2; IR (neat, cm-1) 1751 (s), 1464 (s), 1194 (s); HRMS (ES+)
calcd for C18H23O3 (M + H+) m/z 287.1647, found m/z 287.1652.
Analytical data for benzopyran 5c are as follows: Rf ) 0.63
1
(EtOAc/hexane 1:5); H NMR (400 MHz, CDCl3) δ 6.99 (d, J )
7.6 Hz, 1 H), 6.90 (d, J ) 7.6 Hz, 1 H), 6.82 (t, J ) 7.6 Hz, 1 H),
5.33 (tt, J ) 6.0, 1.6 Hz, 1 H), 4.90 (t, J ) 1.6 Hz, 1 H), 4.88 (s,
1 H), 4.67 (dd, J ) 5.6, 2.0 Hz, 1 H), 4.24 (dq, J ) 7.2, 2.8 Hz,
2 H), 3.38-3.30 (m, 2 H), 2.93-2.76 (m, 3 H), 1.84 (s, 3 H), 1.76
(s, 3 H), 1.71 (s, 3 H), 1.29 (t, J ) 7.2 Hz, 3 H); 13C NMR (100
MHz, CDCl3) δ 170.4, 150.6, 143.6, 132.2, 129.8, 127.4, 126.8,
122.5, 120.5, 120.4, 113.6, 77.2, 61.2, 42.0, 29.7, 28.3, 25.8, 20.3,
17.8, 14.2; IR (neat, cm-1) 1751 (s), 1463 (s), 1194 (s); HRMS
(ES+) calcd for C20H27O3 (M + H+) m/z 315.1960, found m/z
315.1955.
2-(Ethoxycarbonyl)-3-[1-(methoxycarbonyl)-1-ethenyl]-8-[trans-
3-methyl-3-(methoxycarbonyl)-2-propenyl]-3,4-dihydro-2H-1-
benzopyran (5b). Entry 6 (Table 1). To a suspension of the
pallada(II)cycle 3a (0.051 g, 0.100 mmol) in neat methyl (E)-4-
bromo-2-methyl-1-butenoate (0.15 mL, 0.214 g, 1.11 mmol) in a
pressure tube equipped with a magnetic stirring bar was added Cs2-
CO3 (0.081 g, 0.25 mmol). The tube was purged with argon and
capped, and the contents were stirred for 3 h at 100 °C (oil bath).
The reaction mixture was cooled, diluted with methylene chloride,
and filtered though a short plug of Celite, and solvents were
removed under reduced pressure to afford a crude product, which
was separated by flash chromatography over silica with EtOAc/
hexane as eluent ((0.5-1):(9.5-9)) to afford the benzopyran 5b
(0.023 g, 58%) as a colorless oil: Rf ) 0.20 (EtOAc/hexane 1:5);
1H NMR (500 MHz, CDCl3) δ 6.98 (d, J ) 7.5 Hz, 1 H), 6.95-
6.91 (m, 2 H), 6.83 (t, J ) 7.5 Hz, 1 H), 6.32 (s, 1 H), 5.69 (s, 1
H), 4.93 (d, J ) 5.0 Hz, 1 H), 4.21 (q, J ) 7.0 Hz, 2 H), 3.81 (s,
3 H), 3.74 (s, 3 H), 3.53-3.49 (m, 3 H), 2.95 (t, J ) 6.0 Hz, 2 H),
1.95 (d, J ) 1.0 Hz, 3 H), 1.25 (t, J ) 7.0 Hz, 3 H); 13C NMR
(125 MHz, CDCl3) δ 170.1, 168.7, 166.6, 150.5, 140.5, 139.3,
127.9, 127.8, 127.7, 127.4, 126.5, 120.9, 120.0, 76.0, 61.4, 52.1,
51.7, 35.8, 29.2, 28.1, 14.1, 12.5; IR (neat, cm-1) 1716 (br s), 1267
(s), 1195 (s), 740 (s); HRMS (ES+) calcd for C22H27O7 (M + H+)
m/z 403.1757, found m/z 403.1762.
Analytical data for benzopyran 5d are as follows: Rf ) 0.64
1
(EtOAc/hexanes 1:1); H NMR (400 MHz, CDCl3) δ 6.99 (dd, J
) 6.8, 2.0 Hz, 1 H), 6.88-6.82 (m, 2 H), 6.29 (s, 1 H), 5.37 (tt, J
) 7.2, 1.6 Hz, 1 H), 5.28 (s, 1 H), 4.20-4.11 (m, 2 H), 3.38 (d, J
) 7.2 Hz, 2 H), 2.62 (sept, J ) 6.8 Hz, 1 H), 1.76 (s, 3 H), 1.74
(s, 3 H), 1.26-1.18 (m, 9 H); 13C NMR (100 MHz, CDCl3) δ 169.9,
149.6, 138.2, 132.4, 129.0, 128.5, 124.3, 122.5, 121.3, 121.2, 118.3,
75.1, 61.1, 30.7, 27.9, 25.8, 22.1, 20.3, 17.8, 14.0; IR (neat, cm-1
)
1751 (s), 1454 (s), 1184 (s); HRMS (ES+) calcd for C20H27O3 (M
+ H+) m/z 315.1960, found m/z 315.1953.
Procedure for the Recovery of the Palladium(II) Complexes
[N,N′-Bis(cyclohexyl)ethylenediimine]palladium Dibromide (8)
and Bis[bromo(methyl η3-butenoate)palladium(II)] (9). The
crude reaction mixture obtained from the reaction of the pallada-
cycle 3a (0.051 g, 0.100 mmol) with neat methyl trans-4-
bromobutenoate (0.15 mL) at 95 °C for 2 h as described in the
protocols above in the absence of any additive was diluted with
methylene chloride (3.0 mL). The resulting solid was collected by
filtration and washed with cold methylene chloride to afford
complex 8 (0.022 g, 45%) as an orange powder possessing minimal
solubility in common organic solvents: mp 260 °C dec; 1H NMR
(400 MHz, DMSO-d6) δ 7.69 (s br, 2 H), 2.95-1.85 (m, 2 H),
1.87 (d, J ) 7.3 Hz, 4 H), 1.80-1.71 (m, 4 H), 1.58 (d, J ) 12.0
Hz, 2 H), 1.27-1.06 (m, 10 H); IR (KBr, cm-1) 3097 (s), 2937
(s), 2854 (s), 1591 (s), 1473 (s), 1001 (m).
Diffusion-controlled crystallization of complex 8 (N,N-dimethy-
lacetamide/pentane, room temperature, 3 days) afforded a single
crystal suitable for X-ray crystallographic analysis (data provided
in the Supporting Information).
The filtrate obtained by the filtration of the original crude reaction
mixture was collected, and solvents were removed under reduced
2-(Ethoxycarbonyl)-3-(1-methyl-1-ethenyl)-3,4-dihydro-2H-
1-benzopyran (7). Entry 7 (Table 1). To a solution of the pallada-
(II)cycle 3a (0.051 g, 0.10 mmol) in 1,2-dichloroethane (1.0 mL)
in a pressure tube equipped with a magnetic stirring bar was added
neat 3-methyl-1-bromo-2-butene (0.20 mL, 1.70 mmol) and solid
Cs2CO3 (0.050 g, 0.150 mmol). The tube was purged with argon
and capped, and the contents were stirred for 60 h at 105 °C (oil
bath). The reaction mixture was cooled, diluted with methylene
chloride, and filtered though a short plug of Celite, and solvents
were removed under reduced pressure to afford a crude product,
which was separated by flash chromatography over silica with
methylene chloride/hexane (1:9) as eluent to afford the benzopyran
7 (0.014 g, 56%) as a colorless oil: Rf ) 0.57 (EtOAc/hexane 1:5);
1H NMR (500 MHz, CDCl3) δ 7.11 (td, J ) 7.8 Hz, 1.5 Hz, 1 H),

An Allylpalladium(IV) Intermediate
Organometallics, Vol. 26, No. 15, 2007 3883
pressure to afford a crude product, which was separated by flash
chromatography over silica with EtOAc/hexane mixtures as eluent,
with the composition gradually changing from 5% EtOAc to 10%
EtOAc to afford the benzoxepine 4a (0.018 g, 49%), phenol 6 (0.003
g, 17%), and complex 9 (0.004 g, 11%) as a bright yellow solid:
7.32 (t, J ) 7.2 Hz, 1 H), 4.46 (q, J ) 7.1 Hz, 2 H), 3.65 (s, 3 H),
3.39 (t, J ) 7.8 Hz, 2 H), 2.72 (t, J ) 7.8 Hz, 2 H), 1.45 (t, J )
7.2 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 173.0, 160.0, 154.5,
141.1, 128.3, 128.0, 127.9, 123.3, 121.2, 112.3, 61.3, 51.7, 33.9,
19.7, 14.4; IR (neat, cm-1) 1728 (s), 1298 (s), 740 (s); HRMS (ES+)
calcd for C15H17O5 (M + H+) m/z 277.1076 found m/z 277.1068.
1
mp 185 °C dec; Rf ) 0.30 (EtOAc/hexanes 1:5); H NMR (400
MHz, CDCl3) δ 6.16-6.08 (m, 2 H), 4.35 (s br, 2 H), 3.78 (s, 6
H), 3.70 (d, J ) 8.4 Hz, 2 H), 3.32 (d, J ) 13.2 Hz, 2 H); IR
(KBr, cm-1) 1718 (s).
Acknowledgment. Support for this work from the National
Science Foundation via a CAREER Award (Grant No. CHE-
0239123) to H.C.M. is gratefully acknowledged. We thank Dr.
Piyali Datta-Chaudhuri for contributions to earlier stages of this
research and Dr. Douglas R. Powell (University of Oklahoma,
Norman, OK) for his assistance with the crystallographic
analysis of compound 3b.
Diffusion-controlled crystallization of complex 9 (EtOAc/hexane,
room temperature, 3 days) afforded a single crystal suitable for
X-ray crystallographic analysis (data provided in the Supporting
Information).
2-(Ethoxycarbonyl)-3-(methoxycarbonyl)-4,5-dihydro-1-ben-
zoxepine (13a). To a solution of complex 11 (0.100 g, 0.16 mmol)
in acetonitrile (5 mL) in a pressure tube at room temperature under
argon was added 1,4-diazabicyclo[2.2.2]octane (DABCO; 0.0921
g, 0.82 mmol) and triphenylphosphine (0.099 g, 0.38 mmol). The
pressure tube was purged with argon, capped, and heated in an oil
bath (100 °C) for 24 h. The reaction mixture was cooled and filtered
and the solvent was removed under reduced pressure to provide
the crude product, which was purified by flash chromatography
over silica with EtOAc/hexane (1:10) as eluent to afford the
benzoxepine 13a (0.034 g, 76%) as a colorless oil/solid: Rf ) 0.34
Supporting Information Available: Text, figures, tables, and
CIF files giving the general experimental protocol, a description
of X-ray crystallographic studies on compounds 3a,b and 8-12
and their crystal data, 1H and 13C NMR spectra of all new
compounds prepared in this study, including data from 2D NMR
experiments on complex 12, and a description of the experiments
described in Figure 5. This material can be found free of charge
via the Internet at http://pubs.acs.org.
1
(EtOAc/hexane 1:5); H NMR (500 MHz, CDCl3) δ 7.70 (d, J )
7.9 Hz, 1 H), 7.55 (d, J ) 8.3 Hz, 1 H), 7.45 (t, J ) 6.6 Hz, 1 H),
OM7002865