Reactivity of ortho-palladated benzamides toward CO, isocyanides, and alkynes. synthesis of functionalized isoindolin-1-ones and 4,5-disubstituted benzo[ c ]azepine-1,3-diones

Article abstract of DOI:10.1021/om4006406

Aryl palladium complexes [Pd{C₆H₄C(O)NRR′-2} I(tmeda)] [NRR′ = NH₂ (1a), NHMe (1b), NMe₂ (1c); tmeda = N,N,N′,N′-tetramethylethylenediamine] are prepared by oxidative addition of the corresponding 2-iodophenylbenzamides to "Pd(dba)₂" ([Pd₂(dba)₃]·dba; dba = dibenzylideneacetone) in the presence of tmeda. Cationic cyclometalated derivatives [Pd{κ²C,O-C₆H₄C(O)NRR′- 2}(tmeda)]TfO (2a-c) are obtained by iodide abstraction from the appropriate complex 1 with AgTfO, while the deprotonation of the amide function of 1a or 1b with KO^tBu gives the neutral amidate complexes [Pd{κ ²C,N-C₆H₄C(O)NR-2}(tmeda)] [R = H (3a), Me (3b)]. Complexes 2a,b and 3a,b react with CO under mild conditions to yield phthalimide (4a) or N-methylphthalimide (4b), whereas the reactions of derivatives 1c and 2c with CO are very slow and give N¹,N ¹,N²,N²-tetramethylphthalamide and phthalic anhydride. The reaction of 1b with 1 equiv of XyNC (Xy = 2,6-dimethylphenyl) or ^tBuNC affords Pd(0), (tmedaH)I, and 3-(2,6-dimethylphenylimino)-2- methylisoindolin-1-one (5b) or 3-(tert-butylimino)-2-methylisoindolin-1-one (5b′), respectively, while complex 1c reacts with 3 equiv of XyNC to give trans-[Pd{C(i=NXy)C₆H₄C(O)NMe₂-2}I(CNXy) ₂] (6). The seven-membered palladacycles [Pd{κ²C,O- C(X)i=C(X′)C₆H₄C(O)NRR′-2}(tmeda)]TfO [NRR′ = NH₂ and X = Ph, X′ = Me (7a); NRR′ = NHMe and X = Ph, X′ = Me (7b), X = X′ = Ph (8b), Et (9b), CO ₂Me (10b), X = CO₂Me, X′ = Ph (11b), X = CO ₂Et, X′ = Ph (12b); NRR′ = NMe₂ and X = X′ = Ph (8c), Et (9c)] are obtained from the reactions of 2a-c with alkynes. Treatment of complexes 7a, 7b, 8b, and 9b with CO at room temperature gives the corresponding 2H-benzo[c]azepine-1,3-diones (14), resulting from the insertion of a molecule of CO into the Pd-C bond followed by a C-N reductive coupling. In contrast, the reactions of 11b or 12b with CO in the presence of residual water or 2 equiv of ROH (R = Me, Et) lead to 2-methyl-3- phenylisoindolin-1-one derivatives (15), resulting from a CO insertion followed by an intramolecular aza-Michael addition of the NHMe moiety to the activated vinyl group and subsequent hydrolysis or alcoholysis of the acyl-Pd bond. The neutral complex [Pd(κ²C,O-C₁₄H₁₃O ₅)(tmeda)] (18) was synthesized by reacting the cationic derivative 10b with NaOMe in MeOH. Depalladation of 18 gives (E)-4- [methoxy(methoxycarbonyl)methylene]-2-methylisoquinoline-1,3(2H,4H)-dione (19).

Full text of DOI:10.1021/om4006406

Article
pubs.acs.org/Organometallics
Reactivity of Ortho-Palladated Benzamides toward CO, Isocyanides,
and Alkynes. Synthesis of Functionalized Isoindolin-1-ones and 4,5-
Disubstituted Benzo[c]azepine-1,3-diones
Roberto Frutos-Pedreno, Pablo Gonzalez-Herrero,* and Jose Vicente*
́
́
̃
Grupo de Química Organometal
4021, 30071 Murcia, Spain
́
ica, Departamento de Química Inorgan
́
ica, Facultad de Química, Universidad de Murcia, Apartado
Peter G. Jones
Institut fur Anorganische und Analytische Chemie, Technische Universitat Braunschweig, Postfach 3329, 38023 Braunschweig,
̈
̈
Germany
S
* Supporting Information
ABSTRACT: Aryl palladium complexes [Pd{C6H4C(O)NRR′-
2}I(tmeda)] [NRR′ = NH2 (1a), NHMe (1b), NMe2 (1c);
tmeda = N,N,N′,N′-tetramethylethylenediamine] are prepared
by oxidative addition of the corresponding 2-iodophenylbenza-
mides to “Pd(dba)2” ([Pd2(dba)3]·dba; dba = dibenzylidenea-
cetone) in the presence of tmeda. Cationic cyclometalated
derivatives [Pd{κ2C,O-C6H4C(O)NRR′-2}(tmeda)]TfO (2a−
c) are obtained by iodide abstraction from the appropriate
complex 1 with AgTfO, while the deprotonation of the amide
function of 1a or 1b with KOtBu gives the neutral amidate complexes [Pd{κ2C,N-C6H4C(O)NR-2}(tmeda)] [R = H (3a), Me
(3b)]. Complexes 2a,b and 3a,b react with CO under mild conditions to yield phthalimide (4a) or N-methylphthalimide (4b),
whereas the reactions of derivatives 1c and 2c with CO are very slow and give N1,N1,N2,N2-tetramethylphthalamide and phthalic
anhydride. The reaction of 1b with 1 equiv of XyNC (Xy = 2,6-dimethylphenyl) or tBuNC affords Pd(0), (tmedaH)I, and 3-(2,6-
dimethylphenylimino)-2-methylisoindolin-1-one (5b) or 3-(tert-butylimino)-2-methylisoindolin-1-one (5b′), respectively, while
complex 1c reacts with 3 equiv of XyNC to give trans-[Pd{C(NXy)C6H4C(O)NMe2-2}I(CNXy)2] (6). The seven-membered
palladacycles [Pd{κ2C,O-C(X)C(X′)C6H4C(O)NRR′-2}(tmeda)]TfO [NRR′ = NH2 and X = Ph, X′ = Me (7a); NRR′ =
NHMe and X = Ph, X′ = Me (7b), X = X′ = Ph (8b), Et (9b), CO2Me (10b), X = CO2Me, X′ = Ph (11b), X = CO2Et, X′ = Ph
(12b); NRR′ = NMe2 and X = X′ = Ph (8c), Et (9c)] are obtained from the reactions of 2a−c with alkynes. Treatment of
complexes 7a, 7b, 8b, and 9b with CO at room temperature gives the corresponding 2H-benzo[c]azepine-1,3-diones (14),
resulting from the insertion of a molecule of CO into the Pd−C bond followed by a C−N reductive coupling. In contrast, the
reactions of 11b or 12b with CO in the presence of residual water or 2 equiv of ROH (R = Me, Et) lead to 2-methyl-3-
phenylisoindolin-1-one derivatives (15), resulting from a CO insertion followed by an intramolecular aza-Michael addition of the
NHMe moiety to the activated vinyl group and subsequent hydrolysis or alcoholysis of the acyl−Pd bond. The neutral complex
[Pd(κ2C,O-C14H13O5)(tmeda)] (18) was synthesized by reacting the cationic derivative 10b with NaOMe in MeOH.
Depalladation of 18 gives (E)-4-[methoxy(methoxycarbonyl)methylene]-2-methylisoquinoline-1,3(2H,4H)-dione (19).
and five-membered C,O-palladacycles (II).6,8 Deprotonation of
INTRODUCTION
■
the amide function can lead to C,N-palladacyclic amidates
(III).2,7 To the best of our knowledge, there are no examples of
C,N-cyclopalladated arylamides; the coordination of an amide
through the nitrogen is highly unfavorable because the nitrogen
lone pair is conjugated with the carbonyl group, and therefore
amides usually coordinate through the oxygen atom. Several
pincer-type complexes containing the type III structure are also
known.9 Our research group has recently reported the synthesis
Ortho-palladated benzamides are involved as intermediates in
certain palladium-catalyzed C−C and C−heteroatom cross-
coupling processes, including methodologies for the arylation,1
trifluoromethylation,2 and alkenylation3 of benzamides and the
preparation of diverse heterocyclic systems.4−7 Most often, they
are produced by oxidative addition of 2-halobenzamides to
Pd(0) or amide-directed C−H activations by Pd(II). Despite
their important role, only a few of these complexes have been
isolated and structurally characterized, and studies of their
reactivity are very limited. Examples of isolated ortho-palladated
benzamides include acyclic complexes of the type I5,8 (Chart 1)
Received: July 1, 2013
Published: August 8, 2013
© 2013 American Chemical Society
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Chart 1
Scheme 1
of ortho-dipalladated benzamides, as well as C,O-cyclo-
palladated and C,O/C,N-dicyclopalladated (“akimbo”) deriva-
tives (IV−VI).10
As part of our ongoing research on the reactivity of ortho-
functionalized arylpalladium complexes, we have recently
shown that ortho-palladated phenylacetamides11 and 3-phenyl-
propanamides12 undergo C−N reductive coupling after the
insertion of CO or isocyanides into the Pd−C bond, leading to
six- or seven-membered heterocycles under mild conditions.
Eight- and nine-membered heterocycles were also obtained via
sequential insertion of alkynes and CO into the Pd−C bond
followed by reductive C−N coupling.12,13 In this paper, we
report the synthesis of a family of ortho-palladated benzamides
and their C,O- and C,N-palladacyclic derivatives and the study
of their reactivity toward CO, isocyanides, and alkynes, with the
main objective of exploring the feasibility of heterocycle
formation from these systems. A series of new functionalized
isoindoline-1-ones and 4,5-disubstituted benzazepine-1,3-di-
ones have been obtained. Both of these heterocyclic frame-
works are of great importance because they are found in a
variety of bioactive compounds displaying a wide range of
therapeutic activities.14 Benzazepine-1,3-diones are particularly
scarce,15 and, to the best of our knowledge, there are no
precedents for 4,5-disubstituted derivatives.
Complexes 2a,b and 3a,b were treated with CO (1.4 bar) in
order to verify the possible CO insertion/C−N reductive
coupling process. The reactions were complete in about 3 h at
room temperature in acetone-D6 (2a,b) or CDCl3 (3a,b),
quantitatively giving colloidal Pd, (tmedaH)TfO or free tmeda,
and phthalimide (4a, from 2a or 3a) or N-methylphthalimide
(4b, from 2b or 3b). On a preparative scale, these organic
compounds were isolated in ca. 80% yield from 2a or 2b,
respectively.
The reactions of the NMe2 derivative 1c or 2c with CO were
also carried out to check the possible activation of the methyl
groups, which has been shown to be catalyzed by Pd(0) for a
series of 2-bromo-N-alkyl-N-methylbenzamides.5 However,
complete decomposition of these complexes to Pd(0) required
3 days under CO (1.4 bar) at 68 °C in CHCl3 and resulted in
the formation of a mixture of (tmedaH)X (X = I− or TfO−),
phthalic anhydride,17 and N1,N1,N2,N2-tetramethylphthala-
mide,18 which were identified by their NMR data. In addition
to these products, the ESI(+) mass spectrum of the crude
reaction mixture showed a small amount of N,N-dimethyl-
phthalamic acid. It is reasonable to assume that this compound
arises from the hydrolysis of an acyl complex by residual water,
after which it undergoes internal O-cyclization to give phthalic
anhydride and dimethylamine (Scheme 2).19 Further molecules
of the acyl complex can then undergo aminolysis by
dimethylamine to give N1,N1,N2,N2-tetramethylphthalamide.
The reaction of 1b with 1 equiv of XyNC (Xy = 2,6-
RESULTS AND DISCUSSION
■
Synthesis of Ortho-Palladated Benzamides and Cyclo-
metalated Derivatives. Reactions with CO and Isocya-
nides. The aryl palladium complexes [Pd{C6H4C(O)NRR′-
2}I(tmeda)] [NRR′ = NH2 (1a), NHMe (1b), NMe2 (1c);
tmeda = N,N,N′,N′-tetramethylethylenediamine; Scheme 1]
were obtained in moderate yields by oxidative addition of the
corresponding 2-iodobenzamides to “Pd(dba)2” ([Pd2(dba)3]·
dba; dba = dibenzylideneacetone) in the presence of tmeda in
CH2Cl2 at room temperature.
The cationic derivatives [Pd{κ2C,O-C6H4C(O)NRR′-2}-
(tmeda)]TfO (2a−c) were obtained in high yields from 1a−
c via iodide abstraction with AgTfO. In these complexes, the
amide function is coordinated through the oxygen atom, as
usually observed for amide complexes,8,10−13,16 thus forming
five-membered palladacycles.
t
dimethylphenyl) or BuNC at room temperature gave colloidal
Pd, (tmedaH)I, and 3-(2,6-dimethylphenyimino)-2-methyl-
isoindolin-1-one (5b) or 3-(tert-butylimino)-2-methylisoindo-
lin-1-one (5b′), respectively (Scheme 1), which resulted from
the insertion of a molecule of isocyanide into the Pd−C bond
and a subsequent intramolecular C−N coupling. The
intermediate iminoacyl complex could not be isolated because
it rapidly decomposed to give the organic product. Compound
5b was also obtained from 2b and XyNC, but in this case 2
equiv of the isocyanide was required. In contrast, the reaction
of the NH2 derivative 1a or 2a with 1 or 2 equiv, respectively,
Treatment of complex 1a or 1b with KOtBu in MeOH led to
the deprotonation of the amide function and the formation of
the neutral palladacyclic derivatives [Pd{κ2C,N-C6H4C(O)NR-
2}(tmeda)] [R = H (3a), Me (3b)]. These complexes result
from the displacement of the iodo ligand by the nitrogen of the
amidate group and can be isolated in moderate to good yields.
Attempts to deprotonate the methyl group in the NMe2
derivative 1c with KOtBu were unsuccessful.
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TfO (n = 1,13 212). The insertion of alkynes into the Pd−C
bond of aryl complexes requires the coordination of the alkyne
and the migration of the aryl group to the coordinated alkyne.
This process has been shown to be faster as the nucleophilicity
of the metalated arylic carbon increases and when alkynes
bearing smaller substituents or of a higher electron-withdrawing
character are employed.20 The slower alkyne-monoinsertion
reactions of 2a−c can be ascribed to the higher stability of the
five-membered palladacycle, which makes the alkyne coordina-
tion step more difficult, and the lower nucleophilicity of the
metalated arylic carbon caused by the electron-withdrawing
amide function directly bonded to the aryl ring. The required
reaction conditions for each case (Table 1) clearly reflect the
effects of the NRR′ group and the alkyne. For example, the
NMe2 derivative 2c required a lower excess of the alkyne (5-
fold) and a shorter reaction time (1 day) than did the NHMe
derivative 2b for the insertion of diphenylacetylene (10-fold
excess, 5 days), while in the case of the NH2 derivative 2a no
reaction was observed with a 10-fold excess of this alkyne at
room temperature. The attempts to obtain the monoinsertion
products by reacting 2a or 2b with diphenylacetylene at higher
temperatures led to partial decomposition to metallic Pd and
complex mixtures. The increasing reactivity toward the
insertion of alkynes in the order 2a < 2b < 2c can thus be
associated with an increasing nucleophilicity of the metalated
arylic carbon as the number of methyl substituents of the amide
function increases. The effect of the alkyne is also in line with
previously observed trends,20 as the reactions of more
electrophilic or less sterically demanding alkynes with 2a or
2b were faster. Thus, the insertion of 1-phenylpropyne into the
Pd−C bond of 2a was feasible at room temperature, and the
reaction times required in the case of 2b decreased in the
sequence diphenylacetylene > methyl phenylpropiolate ∼ ethyl
phenylpropiolate > 1-phenylpropyne ∼ 3-hexyne ∼ dimethyl-
acetylenedicarboxylate. Compound 2a also reacted with 3-
Scheme 2
of XyNC gave mixtures of two products that could not be
separated, while the NMe2 derivative 1c reacted with 3 equiv of
XyNC to give trans-[Pd{C(NXy)C6H4C(O)NMe2-2}I-
(CNXy)2] (6), resulting from the displacement of the tmeda
ligand by two of the isocyanide molecules and the insertion of a
third isocyanide into the Pd−C bond. Complex 6 was also
obtained when only 1 equiv of isocyanide was employed,
leaving part of the starting complex unreacted.
Insertion of Alkynes. The reactions of palladacycles 2a−c
with a series of internal alkynes XCCX′ at room temperature
afforded good yields of the seven-membered palladacycles
[Pd{κ2C,O-C(X)C(X′)C6H4C(O)NRR′-2}(tmeda)]TfO
[NRR′ = NH2, X = Ph, X′ = Me (7a); NRR′ = NHMe, X = Ph,
X′ = Me (7b), X = X′ = Ph (8b), Et (9b), CO2Me (10b), X =
CO2Me, X′ = Ph (11b), X = CO2Et, X′ = Ph (12b); NRR′ =
NMe2, X = X′ = Ph (8c), Et (9c)], resulting from the insertion
of one molecule of the alkyne into the Pd−C bond (Scheme 3).
These reactions required an excess of the alkyne and reaction
times in the range of 1−5 days to complete and were thus
considerably slower than those of the six- and seven-membered
palladacycles [Pd{κ2C,O-C6H4(CH2)nC(O)NRR′-2}(tmeda)]-
Scheme 3
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Table 1. Molar Ratios, Reaction Times, and Yields of the Alkyne-Monoinsertion Reactions
starting complex
alkyne
1-phenylpropyne
molar ratio
reaction time (h)
product
yield (%)
2a
2b
1:10
1:10
1:10
1:10
1:10
1:10
1:10
1:5
64
24
7a
65
76
74
53
96
71
67
88
87
1-phenylpropyne
diphenylacetylene
3-hexyne
7b
120
24
8b
9b
dimethylacetylenedicarboxylate
methyl phenylpropiolate
ethyl phenylpropiolate
diphenylacetylene
3-hexyne
24
10b
11b
12b
8c
48
48
2c
24
1:5
24
9c
hexyne at room temperature, although the resulting mono-
insertion product is unstable and could not be obtained in pure
form; when the reaction mixture was heated at 40 °C for 24 h, a
partial decomposition to colloidal Pd, (tmedaH)TfO, and 3,4-
diethylisoquinolin-1(2H)-one21 (13) was observed.
at 50 °C gave mixtures of decomposition products. The
complex with inserted DMAD, 10b, also reacted with CO in
CHCl3 at room temperature, but gave a mixture of at least three
compounds that could not be properly identified.
The palladacycles containing inserted phenylpropiolate
derivatives showed a different behavior. Thus, the room-
temperature reaction of 11b with CO (1.4 bar) in CH2Cl2 gave
colloidal Pd, (tmedaH)TfO, and 3-[carboxy-
(methoxycarbonyl)methyl]-2-methyl-3-phenylisoindolin-1-one
(15a). The NMR data of this compound showed two sets of
signals in approximately 1:1 ratio corresponding to the two
possible diastereomeric pairs of enantiomers (see the
Supporting Information). The cyclization to give the
isoindolinone ring is formally the result of an aza-Michael
addition of the NHMe moiety to the vinyl group originating
from the alkyne. This process probably takes place from the
amidate intermediate B (Scheme 3) and is certainly favored
because the vinyl group is highly activated toward conjugated
additions. Similar intramolecular aza-Michael additions of an
amine or amide function to an α,β-unsaturated ester, ketone, or
aldehyde moiety are a key step in several methodologies
employed for the synthesis of isoindolines or isoindolinones.29
Finally, the depalladation step takes place through the
hydrolysis of the acyl−Pd bond by residual water. Our attempts
to isolate compound 15a from the reaction mixture were
unsuccessful because decarboxylation easily occurred to give 3-
(methoxycarbonylmethyl)-2-methyl-3-phenylisoindolin-1-one
(16); indeed, the latter compound was obtained in pure form
after refluxing the reaction mixture in CH2Cl2 for 24 h. The
facile decarboxylation of phenylmalonic diacids and hemiesters
is well known.30
When the reaction of 11b with CO was carried out in the
presence of 2 equiv of MeOH or EtOH, the same process took
place, but in these cases the depalladation step is an alcoholysis
leading to the diester 3-[di(methoxycarbonyl)methyl]-2-meth-
yl-3-phenylisoindolin-1-one (15b) or 3-[ethoxycarbonyl-
(methoxycarbonyl)methyl]-2-methyl-3-phenylisoindolin-1-one
(15c), respectively. Analogously, the reactions of 12b with CO
in the presence of 2 equiv of MeOH or EtOH gave 15c or 3-
[di(ethoxycarbonyl)methyl]-2-methyl-3-phenylisoindolin-1-
one (15d), respectively.
The use of MeOH as solvent for the reaction of 11b and CO
led to the formation of dimethyl 2-((2-(methylcarbamoyl)-
phenyl)(phenyl)methylene)malonate (17), resulting from the
methanolysis of the intermediate acyl complex A, and only trace
quantities of the heterocyclic compound 15b were detected in
the reaction mixture. Logically, in the presence of a large excess
of MeOH, the methanolysis of A is much faster than the
cyclization. The attempt to cyclize 17 by heating a CDCl3
solution at 70 °C for 24 h in the presence of an excess of tmeda
Di- or triinsertion products were not observed in any of the
cases, which is striking considering the presence of an excess of
alkyne and the larger size of palladacycles 7−12, which should
facilitate the ring-opening and the coordination of additional
alkyne molecules. This is possibly associated with the relatively
low nucleophilicity of the vinylic carbon bonded to Pd, because
of the electron-withdrawing effect of the amide carbonyl group.
The regiochemistry of the insertions of the unsymmetrical
alkynes 1-phenylpropyne, methyl phenylpropiolate, and ethyl
phenylpropiolate was established by means of 1H/13C
heteronuclear multiple-bond correlation (HMBC) experiments
and confirmed by the crystal structures of 7a and 11b (see
below). We have reviewed the regiochemistry of the insertion
of alkynes into the Pd−C bond of aryl palladium complexes.22
The insertion of 1-phenylpropyne led to only the regioisomer
with the most sterically demanding substituent in the α-
position with respect to the metal (7a,b), which is the usual
pattern observed for the insertion of unsymmetrical
alkynes.23,24 However, methyl and ethyl phenylpropiolate led
to an approximately 1:0.2 mixture of regioisomers, the major
one with the ester group in the α-position, and only this
regioisomer was isolated after workup (11b, 12b). The
insertion of phenylpropiolate derivatives into the Pd−C bond
of five-membered palladacycles has previously been shown to
give preferentially the regioisomer with the ester group in the β-
position.25 We have recently shown this also to be the case for
six-membered palladacycles.24 Nevertheless, this pattern can be
reversed for palladacycles with weakly chelating aryl
ligands,22,26,27 such as 2a−c, or a highly electron-deficient
character.27,28
Reactions of Alkyne-Monoinsertion Products with
CO. Palladacycles 7a, 7b, 8b, and 9b reacted with CO (1.4
bar) at room temperature in CHCl3 to give colloidal Pd,
(tmedaH)TfO, and the corresponding 4,5-disubstituted benzo-
[c]azepine-1,3-diones 14 (Scheme 3), resulting from a CO
insertion/C−N reductive coupling sequence. The formation of
these derivatives probably involves an eight-membered cyclic
acyl intermediate A, in equilibrium with the amidate B,
resulting from the deprotonation of the amide function. The
latter would ultimately undergo the C−N reductive coupling.
In line with our previous observations,11−13 the NHMe
derivatives 7−9b required a longer reaction time (24 h) than
did the NH2 derivative 7a (3 h), because the steric repulsion of
the methyl substituent makes the C−N coupling slower. The
reactions of the NMe2 derivatives 8c and 9c with CO in CHCl3
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was unsuccessful, suggesting that the aza-Michael addition
leading to 15a−d is assisted by the Pd(II) center, which is
consistent with the participation of an amidate intermediate.
Formation and Depalladation of a Neutral Alkyl-
Alcoholate Complex. The deprotonation of the amide
function in complex 10b with NaOMe was attempted in
order to obtain a seven-membered cyclic amidate and use it as a
precursor for the preparation of an additional benzo[c]azepine-
1,3-dione derivative. However, the reaction of this complex
with excess NaOMe in MeOH led to the formation of the
unexpected neutral complex [Pd(κ2C,O-C14H13O5)(tmeda)]
(18), which contains a chelating alkyl-alcoholate ligand based
on the isoquinoline-1,3-dione scaffold (Scheme 4). The
formation of this ligand must involve the nucleophilic attack
of an amidate group (intermediate C) to the ester group in β
with respect to the metal to generate a six-membered cyclic
imide (D). Subsequently a methoxide anion would attack the
metalated carbon atom.
The depalladation of complex 18 was achieved by refluxing it
in CHCl3 for 2 d and led to the organic compound (E)-4-
[methoxy(methoxycarbonyl)methylene]-2-methylisoquinoline-
1,3(2H,4H)-dione (19). The same product was observed by 1H
NMR after reacting complex 18 with CO (1.4 bar) in CDCl3
for 6 h at room temperature (93%). In this case the insertion of
CO into the Pd−C bond did not take place, but probably the
excess CO assisted the reduction process.
Crystal Structures. The structure of 2a is shown in Figure
1. The amide group is coordinated to the Pd atom through the
oxygen, forming a practically planar five-membered C,O-
palladacycle [mean deviation from plane Pd−C1−C2−C7−
O1: 0.03 Å]. The square-planar coordination environment
around the Pd center is slightly distorted, because of the small
bite of both the chelating benzamide unit [angle C(1)−Pd−
O(1): 82.38(6)°] and the tmeda ligand [angle N(2)−Pd−
N(3): 85.43(7)°]. The Pd−O(1) bond distance of 2.0220(12)
Å is similar to that found for the ortho-palladated benzamide
derivative [Pd{κ2C,O-C6H4{C(O)NHtBu}-6-(OMe)3-2,3,4}-
(bpy)]TfO [2.009(2) Å].8 The two H atoms of the NH2
group are involved in hydrogen bonds with two oxygen atoms
of different triflate anions, forming infinite chains parallel to
[110].
Scheme 4
The amidate group of 3a is coordinated to the Pd atom
through the nitrogen atom, forming an almost planar (mean
deviation: 0.05 Å) five-membered ring (Figure 2). The Pd−
N(1) bond distance of 1.9943(16) Å is similar to or slightly
shorter than that found for previously reported five-,10,31
six-,11,32 or seven-membered12 cyclic palladium amidate
complexes. The O(1)−C(7) bond distance of 1.252(2) Å is
longer than the average C−O distance found in amides (1.234
Å),33 as expected because of the delocalization of the negative
charge over the N−CO group. The molecules are connected
Figure 1. Left: Thermal ellipsoid plot (50% probability) of complex 2a. Selected bond distances (Å) and angles (deg): Pd−C(1) 2.0025(18), Pd−
O(1) 2.0220(12), Pd−N(2) 2.0728(15), Pd−N(3) 2.1494(16), O(1)−C(7) 1.272(2), N(1)−C(7) 1.318(2); C(1)−Pd−O(1) 82.38(6), N(2)−
Pd−N(3) 85.43(7), C(7)−O(1)−Pd 114.03(11), O(1)−C(7)−C(2) 118.02(15), N(1)−C(7)−C(2) 123.10(16). Right: Chain of residues
connected by hydrogen bonds (dashed bonds).
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Figure 2. Thermal ellipsoid plot (50% probability) of complex 3a.
Selected bond distances (Å) and angles (deg): Pd−N(1) 1.9943(16),
Pd−C(1) 2.0058(15), Pd−N(2) 2.1228(16), Pd−N(3) 2.1575(14),
O(1)−C(7) 1.252(2), N(1)−C(7) 1.328(2); N(1)−Pd−C(1)
80.56(6), N(2)−Pd−N(3) 84.15(6), C(7)−N(1)−Pd(1)
119.03(12), O(1)−C(7)−C(2) 122.59(15), N(1)−C(7)−C(2)
110.83(15).
to form inversion-symmetric dimers by a hydrogen bond N1−
H01···O1.
The crystal structures of complexes 7a (Figure 3) and 11b
(Figure 4) show that the 1-phenylpropyne or methyl
phenylpropiolate molecule, respectively, has inserted in a syn
fashion and the amide function remains coordinated to the
metal through the oxygen. The resulting ring shows a folded
conformation dictated by the constraints of the planar vinyl,
benzene, and amide groups; the atoms C1, C2, C9, and O1 are
essentially coplanar, with the atoms Pd, C3, and C4 lying ca.
1.2, 0.9, and 0.9 Å to the same side of the plane. The Pd atom is
in a square planar environment, slightly distorted by the small
bite of the tmeda ligand and the strain of the seven-membered
ring. The latter leads to a C(1)−Pd−O(1) angle of 86.17(7)°
(7a) or 85.50(6)° (11b), which is appreciably narrower than
the corresponding angle in the larger palladacycles [Pd{κ2C,O-
C(Ph)C(Ph)C6H4(CH2)nC(O)NH2-2}(tmeda)]TfO (n = 1,
94.00°;13 n = 2, 90.47°12). In 7a, the H atoms of the NH2 group
are involved in hydrogen bonds with one oxygen atom of a
triflate anion and another oxygen atom of an adjacent molecule,
forming inversion-symmetric dimers. In 11b, the NHMe group
is connected to the triflate anion through a hydrogen bond.
The crystal structure of compound 14b is shown in Figure 5.
The seven-membered ring shows a twisted conformation (N2,
C3, C4 lie 0.7, 1.4, 0.65 Å to the same side of the plane C1−
C9A−C5A−C5) involving a nonplanar imide group (angle of
48° between the C(9A)−C(1)−O(1)−N(2) and C(4)−C(3)−
O(2)−N(2) mean planes). Only a few structures of cyclic
imides of this size have been reported to date, and these display
a similar conformation.34
Figure 3. Above: Thermal ellipsoid plot (50% probability) of complex
7a. Selected bond distances (Å) and angles (deg): Pd−C(1)
1.9936(19), Pd−O(1) 2.0525(13), Pd−N(2) 2.0672(16), Pd−N(3)
2.1715(17), O(1)−C(9) 1.266(2), N(1)−C(9) 1.317(3), C(1)−C(2)
1.344(3); C(1)−Pd−O(1) 86.17(7), N(2)−Pd−N(3) 85.37(6),
C(9)−O(1)−Pd 120.42(13), C(2)−C(1)−Pd 118.94(15), C(1)−
C(2)−C(3) 120.85(18), O(1)−C(9)−C(4) 122.54(17), N(1)−
C(9)−C(4) 118.43(18). Below: Inversion-symmetric dimer of 7a
connected by hydrogen bonds (dashed lines).
Compound 15b crystallized with two independent molecules
in the asymmetric unit (Figure 6), for which a least-squares fit
gave an rms deviation of 0.28 Å. The bond distances and angles
within the isoindoline fragment are comparable to those found
in analogous compounds.35
The structure of complex 18 (Figure 7) proved to be a
CH2Cl2 monosolvate. It shows the isoquinoline-1,3-dione-
based ligand coordinated through one of the oxygen atoms and
the deprotonated methoxy(methoxycarbonyl)methyl group,
forming a nearly planar five-membered palladacycle (mean
deviation 0.04 Å). The Pd−O(1) distance of 2.0267(11) Å is
Figure 4. Thermal ellipsoid plot (50% probability) the cation of
complex 11b. Selected bond distances (Å) and angles (deg): Pd−C(1)
1.9962(18), Pd−O(1) 2.0580(12), Pd−N(2) 2.0628(15), Pd−N(3)
2.1474(15), C(1)−C(2) 1.345(3), C(9)−O(1) 1.265(2); C(1)−Pd−
O(1) 85.50(6), N(2)−Pd−N(3) 85.14(6), C(2)−C(1)−C(10)
124.58(17), C(2)−C(1)−Pd 119.59(14), C(9)−O(1)−Pd
117.92(12), C(1)−C(2)−C(3) 119.39(17), O(1)−C(9)−N(1)
120.28(17), O(1)−C(9)−C(4) 123.27(16).
comparable to that found in some Pd(II) phenolato
complexes.36
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Figure 5. Thermal ellipsoid plot (50% probability) of compound 14b.
Selected bond distances (Å) and angles (deg): C(1)−O(1)
1.2194(12), C(1)−N(2) 1.3901(13), C(1)−C(9A) 1.4982(14),
N(2)−C(3) 1.4036(13), C(3)−O(2) 1.2164(12), C(3)−C(4)
1.4941(13), C(4)−C(5) 1.3458(14); O(1)−C(1)−N(2) 119.25(9),
O(1)−C(1)−C(9A) 120.27(9), N(2)−C(1)−C(9A) 120.06(8),
C(1)−N(2)−C(3) 126.46(8), O(2)−C(3)−N(2) 119.37(9), O(2)−
C(3)−C(4) 120.86(9), N(2)−C(3)−C(4) 118.85(8), C(5)−C(4)−
C(3) 125.71(9), C(4)−C(5)−C(5A) 123.11(9).
Figure 7. Thermal ellipsoid plot (50% probability) of complex 18.
Selected bond distances (Å) and angles (deg): Pd−O(1) 2.0267(11),
Pd−C(10) 2.0635(14), Pd−N(3) 2.1058(12), Pd−N(4) 2.1783(12),
C(1)−O(2) 1.2422(19), C(1)−N(2) 1.388(2), N(2)−C(3)
1.3967(19), C(3)−O(1) 1.3075(18), C(3)−C(4) 1.368(2), C(4)−
C(10) 1.507(2); O(1)−Pd−C(10) 84.38(5), N(3)−Pd−N(4)
83.42(5), C(4)−C(10)−Pd(1) 105.48(9), C(3)−O(1)−Pd
110.72(10), C(1)−N(2)−C(3) 122.90(13), O(1)−C(3)−C(4)
122.66(15), O(1)−C(3)−N(2) 116.22(14), C(4)−C(3)−N(2)
121.10(15), C(3)−C(4)−C(10) 115.87(14), C(3)−C(4)−C(4A)
119.76(15).
Figure 6. Thermal ellipsoid plot (50% probability) of compound 15b.
Selected bond distances (Å) and angles (deg): O(1)−C(3)
1.2290(15), C(1)−N(2) 1.4877(15), C(1)−C(7A) 1.5303(17),
N(2)−C(3) 1.3591(16), C(3)−C(3A) 1.4763(18), C(3A)−C(7A)
1.3883(17); N(2)−C(1)−C(7A) 100.41(9), N(2)−C(1)−C(21)
109.52(9), C(7A)−C(1)−C(21) 113.89(10), N(2)−C(1)−C(8)
107.48(9), C(7A)−C(1)−C(8) 112.89(10), C(21)−C(1)−C(8)
111.81(10), C(3)−N(2)−C(2) 121.38(10), C(3)−N(2)−C(1)
113.92(10), C(2)−N(2)−C(1) 124.33(10), O(1)−C(3)−N(2)
125.31(12), O(1)−C(3)−C(3A) 128.18(12), N(2)−C(3)−C(3A)
106.50(10).
Figure 8. Thermal ellipsoid plot (50% probability) of compound 19.
Selected bond distances (Å) and angles (deg): O(1)−C(1)
1.2194(14), O(2)−C(3) 1.2285(14), C(1)−N(2) 1.3917(14),
C(1)−C(8A) 1.4820(15), N(2)−C(3) 1.3823(14), C(3)−C(4)
1.4838(15), C(4)−C(9) 1.3573(16), C(4)−C(4A) 1.4707(15);
O(1)−C(1)−N(2) 120.45(10), O(1)−C(1)−C(8A) 122.68(10),
N(2)−C(1)−C(8A) 116.86(9), C(3)−N(2)−C(1) 125.01(9),
C(3)−N(2)−C(2) 116.94(9), C(1)−N(2)−C(2) 118.03(9), O(2)−
C(3)−N(2) 119.41(10), O(2)−C(3)−C(4) 122.24(10), N(2)−
C(3)−C(4) 118.34(10), C(9)−C(4)−C(4A) 126.22(10), C(9)−
C(4)−C(3) 114.69(10), C(4A)−C(4)−C(3) 119.08(10).
The crystal structure of compound 19 (Figure 8) reveals that
the C4−C9 double bond has an E configuration, which must be
the most sterically favored.
conditions, leading to the formation of isoindoline-1,3-diones
(phthalimides) or 3-iminoisoindolin-1-ones.
Cationic C,O-cyclopalladated benzamides react with internal
alkynes to give seven-membered palladacycles resulting from
the insertion of the alkyne into the Pd−C bond. These
insertions are, in general, much slower than those from
analogous cyclopalladated phenylacetamides and 3-phenyl-
propanamides previously reported by us, presumably because
of the higher stability of the five-membered palladacyclic
precursors and the lower nucleophilicity of the metalated
carbon of the benzamide. In addition, the substitution degree of
the amidic nitrogen clearly affects the rate of the insertion
CONCLUSIONS
■
Ortho-palladated benzamides can be obtained by oxidative
addition of 2-iodobenzamide or its N-methyl- or N,N-dimethyl-
substituted derivatives to Pd(dba)2 in the presence of tmeda.
Five-membered cationic C,O- or neutral C,N-palladacyclic
derivatives are easily accessible via iodide abstraction or
deprotonation of the NH2 or NHMe group, respectively. The
insertion of CO or isocyanides into the Pd−C bond of some of
these complexes triggers C−N reductive coupling under mild
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formation of a precipitate, which was filtered off, washed with a 1:2
MeOH/Et2O mixture (3 × 5 mL) (1a) or Et2O (3 × 5 mL) (1b,c),
and vacuum-dried to give the corresponding complex 1.
reaction, which increases significantly with the number of
methyl substituents. Two different types of heterocyclic
compounds can be obtained from the reactions of the enlarged
palladacycles with CO, depending on the nature of the inserted
alkyne. Thus, the complexes containing inserted 1-phenyl-
propyne, diphenylacetylene, or 3-hexyne (NH2 or NHMe
derivatives) lead to 4,5-disubstituted benzo[c]azepine-1,3-
diones, resulting from a CO insertion into the Pd−C bond
followed by a C−N reductive coupling. For the complexes with
inserted methyl or ethyl phenylpropiolate (NHMe derivatives),
an aza-Michael addition of the NHMe moiety to the vinyl
group takes place after the insertion of CO, finally leading to
the formation of isoindolin-1-one derivatives.
1a. Yellow solid. Yield: 53%. Anal. Calcd for C13H22IN3OPd: C,
33.25; H, 4.72; N, 8.95. Found: C, 33.34; H, 4.80; N, 8.60. Mp: 130−
1
132 °C (dec). IR (Nujol, cm−1): ν(NH), 3307; ν(CO), 1647. H
NMR (400.9 MHz, CDCl3): δ 8.26 (br s, 1 H, NH), 7.63 (dd, 4JHH
=
3
4
3
1.6 Hz, JHH = 7.6 Hz, 1 H, Ar), 7.55 (dd, JHH = 1.2 Hz, JHH = 7.6
Hz, 1 H, Ar), 7.03 (td, 4JHH = 1.6 Hz, 3JHH = 7.6 Hz, 1 H, Ar), 6.93 (td,
4JHH = 1.2 Hz, 3JHH = 7.6 Hz, 1 H, Ar), 6.02 (br s, 1 H, NH), 2.73 (br
s, 6 H, Me), 2.82−2.59 (m, 4 H, CH2), 2.27 (br s, 6 H, Me). 13C{1H}
NMR (50.3 MHz, CDCl3): δ 172.7 (CO), 144.0, 140.1 (C, Ar), 137.6,
129.3, 128.7, 123.4 (CH, Ar), 62.2, 58.5 (CH2), 50.0 (br, Me).
1b. Yellow solid. Yield: 62%. Anal. Calcd for C14H24IN3OPd: C,
34.76; H, 5.00; N, 8.69. Found: C, 34.77; H, 4.68; N, 8.66. Mp: 158−
1
161 °C (dec). IR (Nujol, cm−1): ν(NH), 3321; ν(CO), 1650. H
3
EXPERIMENTAL SECTION
NMR (400.9 MHz, CDCl3): δ 8.22 (br q, JHH = 4.8 Hz, 1 H, NH),
■
7.56 (dd, 4JHH = 1.6 Hz, 3JHH = 7.6 Hz, 1 H, Ar), 7.50 (dd, 4JHH = 0.8
Hz, 3JHH = 7.6 Hz, 1 H, Ar), 6.99 (td, 4JHH = 1.6 Hz, 3JHH = 7.6 Hz, 1
H, Ar), 6.91 (td, 4JHH = 0.8 Hz, 3JHH = 7.6 Hz, 1 H, Ar), 3.08 (d, 3JHH
= 4.8 Hz 1 H, NHMe), 2.72 (br s, 6 H, Me, tmeda), 2.72−2.58 (m, 4
H, CH2, tmeda), 2.22 (br s, 6 H, Me, tmeda). 13C{1H} APT NMR
(100.8 MHz, CDCl3): δ 171.0 (CO), 142.6, 140.9 (C, Ar), 137.4,
128.9, 128.2, 123.3 (CH, Ar), 62.2, 58.4 (CH2), 50.1 (br, Me, tmeda),
26.3 (NHMe).
General Considerations, Materials, and Instrumentation.
Unless otherwise noted, all preparations were carried out at room
temperature under atmospheric conditions. Synthesis grade solvents
were obtained from commercial sources. CH2Cl2 was degassed and
dried using a Pure Solv MD-5 solvent purification system from
Innovative Technology, Inc. The compound [Pd2(dba)3]·dba was
prepared according to the published procedure.37 The preparations of
2-iodo-N-methylbenzamide and 2-iodo-N,N-dimethylbenzamide are
given in the Supporting Information. All other reagents were obtained
from commercial sources and used without further purification. NMR
spectra were recorded on Bruker Avance 200, 300, or 400
spectrometers at 298 K. Chemical shifts are referred to internal
1c. Pale orange solid. Yield: 51%. Anal. Calcd for C15H26IN3OPd:
C, 36.20; H, 5.27; N, 8.44. Found: C, 36.25; H, 5.18; N, 8.40. Mp:
1
165−168 °C (dec). IR (Nujol, cm−1): ν(CO), 1612. H NMR (400.9
MHz, CDCl3): δ 7.27 (dd, 4JHH = 1.2 Hz, 3JHH = 7.2 Hz, 1 H, Ar), 6.96
(m, 1 H, Ar), 6.86 (m, 1 H, Ar), 6.80 (td, 4JHH = 1.2 Hz, 3JHH = 7.2 Hz,
1 H, Ar), 3.27−3.20 (m, 1 H, CH2), 3.08 (s, 3 H, Me, benzamide),
2.93 (s, 3 H, Me, benzamide), 2.77 (m, 1 H, CH2), 2.71 (s, 3 H, Me,
tmeda), 2.68 (s, 3 H, Me, tmeda), 2.61 (s, 3 H, Me, tmeda), 2.37−2.30
(m, 2 H, CH2), 2.19 (s, 3 H, Me, tmeda). 13C{1H} APT NMR (100.8
MHz, CDCl3): δ 175.0 (CO), 144.3, 143.1 (C, Ar), 135.4, 127.0,
125.0, 121.8 (CH, Ar), 61.5, 58.4 (CH2), 51.4, 51.2, 48.3, 47.7 (Me,
tmeda), 40.4, 35.4 (Me, benzamide).
1
TMS. The assignments of the H and 13C{1H} NMR spectra were
made with the help of HMBC and HMQC experiments. Inserted and
coordinated XyNC are denoted by XyNCi and XyNCc, respectively,
and the 1,2-C6H4 arylene group is denoted by Ar. Melting points were
determined on a Reichert apparatus and are uncorrected. Elemental
analyses were carried out with Carlo Erba 1106 and LECO CHNS-932
microanalyzers. Infrared spectra were recorded in the range 4000−200
cm−1 on a Perkin-Elmer Spectrum 100 spectrophotometer using Nujol
mulls between polyethylene sheets or CH2Cl2 solutions. High-
resolution ESI mass spectra were recorded on an Agilent 6220
Accurate-Mass TOF LC/MS.
Synthesis of [Pd{κ2C,O-C6H4C(O)NRR′-2}(tmeda)]TfO [NRR′ =
NH2 (2a), NHMe (2b), NMe2 (2c)]. To a suspension of the
appropriate complex 1 (1.02 mmol) in acetone (15 mL) was added
AgTfO (1.02 mmol). The mixture was stirred for 30 min and filtered
through Celite. Partial evaporation of the filtrate (2 mL) and addition
of Et2O (20 mL) led to the precipitation of a colorless solid, which was
collected by filtration, washed with Et2O (5 × 3 mL), and vacuum-
dried to give 2.
X-ray Structure Determinations. Crystals suitable for X-ray
diffraction studies were obtained by liquid−liquid diffusion from
acetone/Et2O (2a), CH2Cl2/Et2O (3a), CH2Cl2/Et2O (7a), CDCl3/
Et2O (11b), CDCl3/n-hexane (15b), or CH2Cl2/n-hexane (18·
CH2Cl2) or by sublimation at low pressure (14b and 19). Numerical
details are given in the Supporting Information (Tables S1 and S2).
The data for 3a, 7a, 11b, 15b, and 18·CH2Cl2 were collected on an
Oxford Diffraction Xcalibur E diffractometer using monochromated
Mo Kα radiation in ω-scan mode. The data for 2a, 14b, and 19 were
collected on an Oxford Diffraction Nova A diffractometer using
mirror-focused Cu Kα radiation in ω-scan mode. Absorption
corrections were based on multiscans. The structures were solved by
direct methods and refined anisotropically on F2 using the program
2a. Yield: 94%. Anal. Calcd for C14H22F3N3O4PdS: C, 34.19; H,
4.51; N, 8.54; S, 6.52. Found: C, 34.10; H, 4.77; N, 8.42; S, 6.08. Mp:
179−181 °C (dec). IR (Nujol, cm−1): ν(NH), 3334, 3215, 3180;
1
ν(CO), 1663. H NMR (400.9 MHz, (CD3)2CO): δ 8.76 (br, 1 H,
NH), 8.34 (br, 1 H, NH), 7.66 (m, 1 H, Ar), 7.40−7.35 (m, 2 H, Ar),
7.22−7.18 (m, 1 H, Ar), 3.13−3.10 (m, 2 H, CH2), 3.06 (s, 6 H, Me),
2.92−2.89 (m, 2 H, CH2), 2.75 (s, 6 H, Me). 13C{1H} APT NMR
(75.5 MHz, (CD3)2CO): δ 183.8 (CO), 153.8, 142.0 (C, Ar), 133.2,
133.0, 127.8, 125.9 (CH, Ar), 65.9, 58.2 (CH2), 52.1, 47.8 (Me).
2b. Yield: 91%. Anal. Calcd for C15H24F3N3O4PdS: C, 35.62; H,
4.78; N, 8.31; S, 6.34. Found: C, 35.65; H, 4.87; N, 8.31; S, 6.12. Mp:
209−210 °C (dec). IR (Nujol, cm−1): ν(NH), 3283; ν(CO), 1615. 1H
NMR (400.9 MHz, (CD3)2CO): δ 9.04 (br, 1 H, NH), 7.57 (m, 1 H,
Ar), 7.36−7.31 (m, 2 H, Ar), 7.21−7.14 (m, 1 H, Ar), 3.14−3.11 (m, 2
SHELXL-97 (G. M. Sheldrick, University of Gottingen).38 Treatment
̈
of hydrogen atoms was as follows: NH (where present) freely refined,
methyls as idealized rigid groups allowed to rotate but not tip, other H
using a riding model starting from calculated positions.
Exceptions and Special Features. The Flack parameter refined to
−0.019(4) for 2a and −0.025(12) for 18. For 15b, no absorption
correction was applied. For 3a, a significant isolated difference peak
near the 2-fold axis was tentatively refined as a water oxygen, but no
water hydrogens were located.
Synthesis of [Pd{C6H4C(O)NRR′-2}I(tmeda)] [NRR′ = NH2 (1a),
NHMe (1b), NMe2 (1c)]. To a suspension of Pd(dba)2 (1234 mg,
2.15 mmol) in CH2Cl2 (20 mL) were added tmeda (0.4 mL, 2.66
mmol) and 2-iodobenzamide, 2-iodo-N-methylbenzamide, or 2-iodo-
N,N-dimethylbenzamide (2.15 mmol), and the mixture was stirred for
90 min under an N2 atmosphere. The resulting black suspension was
filtered through anhydrous MgSO4, and the clear orange filtrate was
concentrated (1 mL). The addition of Et2O (20 mL) led to the
3
H, CH2), 3.07 (s, 6 H, Me, tmeda), 3.06 (d, JHH = 4.4 Hz, 3 H,
NHMe), 2.94−2.91 (m, 2 H, CH2), 2.82 (s, 6 H, Me, tmeda). 13C{1H}
APT NMR (75.5 MHz, (CD3)2CO): δ 180.7 (CO), 152.6, 142.3 (C,
Ar), 132.9, 132.7, 126.5, 125.9 (CH, Ar), 66.0, 58.1 (CH2), 52.1, 48.0
(Me, tmeda), 27.1 (NHMe).
2c. Yield: 91%. Anal. Calcd for C16H26F3N3O4PdS: C, 36.97; H,
5.04; N, 8.08; S, 6.17. Found: C, 36.90; H, 4.75; N, 8.09; S, 6.54. Mp:
132−133 °C. IR (Nujol, cm−1): ν(CO), 1586. 1H NMR (400.9 MHz,
4
(CD3)2CO): δ 7.64 (dd, JHH = 1.2 Hz, 3JHH = 7.6 Hz, 1 H, Ar), 7.39
4
3
4
(dd, JHH = 1.2 Hz, JHH = 7.6 Hz, 1 H, Ar), 7.33 (td, JHH = 1.2 Hz,
3JHH = 7.6 Hz, 1 H, Ar), 7.19 (ddd, 4JHH = 1.2 Hz, 3JHH = 7.2 Hz, 3JHH
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4
3
= 7.6 Hz, 1 H, Ar), 3.63 (s, 3 H, Me, benzamide), 3.30 (s, 3 H, Me,
benzamide), 3.14−3.11 (m, 2 H, CH2), 3.05 (s, 6 H, Me, tmeda),
2.91−2.88 (m, 2 H, CH2), 2.79 (s, 6 H, Me, tmeda). 13C{1H} APT
NMR (75.5 MHz, (CD3)2CO): δ 180.6 (CO), 153.7, 141.9 (C, Ar),
133.1, 132.0, 130.1, 125.4 (CH, Ar), 66.0, 58.0 (CH2), 52.0, 48.1 (Me,
tmeda), 41.9, 39.1 (Me, benzamide).
MHz, CDCl3): δ 7.84 (m, 1 H, H7), 7.52 (td, JHH = 0.8 Hz, JHH
=
7.6 Hz, 1 H, H6), 7.31 (td, 4JHH = 0.8 Hz, 3JHH = 7.6 Hz, H5), 7.11 (br
d, 3JHH = 7.6 Hz, 2 H, m-H, Xy), 7.03−6.98 (m, 1 H, p-H, Xy), 6.50 (d,
3JHH = 7.6 Hz, 1 H, H4), 3.43 (s, 3 H, NMe), 2.04 (s, 6 H, Me, Xy).
13C{1H} APT NMR (100.8 MHz, CDCl3): δ 167.8 (CO), 151.3 (C
N), 146.0 (i-C, Xy), 133.2 (C5), 132.2 (C7a), 132.0 (C7), 130.1
(C3a), 128.3 (m-C, Xy), 126.7 (o-C, Xy), 123.8 (C4), 123.7 (p-C, Xy),
123.1 (C7), 25.2 (NMe), 18.1 (Me, Xy).
Synthesis of [Pd{κ2C,N-C6H4C(O)NR-2}(tmeda)] [R = H (3a),
Me (3b)]. To a solution of the appropriate complex 1 (0.40 mmol) in
MeOH (20 mL) was added KOtBu (0.45 mmol), and the mixture was
stirred for 1 h. The solvent was removed under reduced pressure, and
the residue was extracted with CH2Cl2 (6 × 5 mL); the combined
extracts were filtered through anhydrous MgSO4. Partial evaporation
of the filtrate (2 mL) and slow addition of n-pentane (20 mL) led to
the formation of a pale yellow precipitate, which was filtered off,
washed with n-pentane (3 × 3 mL), and vacuum-dried to give the
corresponding complex 3.
Synthesis of 3-(tert-Butylimino)-2-methylisoindolin-1-one
(5b′). This compound was obtained as a colorless solid using the
procedure described for 5b (method A), from 1b (148 mg, 0.31
t
mmol) and BuNC (35 μL, 0.31 mmol). Yield: 50 mg, 76%. Anal.
Calcd for C13H16N2O: C, 72.19; H, 7.46; N, 12.95. Found: C, 72.11;
H, 7.29; N, 12.92. Mp: 133−135 °C. IR (Nujol, cm−1): ν(CO), 1728;
ν(CN), 1650. HRMS (ESI+, m/z): exact mass calcd for C13H17N2O
[M + H]+ requires 217.1335, found 217.1335, error = 0.03 ppm. H
1
3
3a. Yield: 88%. Anal. Calcd for C13H21N3OPd: C, 45.69; H, 6.19;
NMR (400.9 MHz, CDCl3): δ 7.99 (br d, JHH = 7.6 Hz, 1 H, H7),
4
3
N, 12.30. Found: C, 45.55; H, 6.25; N, 12.17. Mp: 183−184 °C. IR
7.89 (m, 1 H, H4), 7.62 (td, JHH = 1.6 Hz, JHH = 7.6 Hz, 1 H, H6),
1
(Nujol, cm−1): ν(NH), 3252; ν(CO), 1608. H NMR (300.1 MHz,
7.58 (td, 4JHH = 1.6 Hz, 3JHH = 7.6 Hz, 1 H, H5), 3.18 (s, 3 H, NMe),
1.55 (s, 9 H, Bu). 13C{1H} APT NMR (75.5 MHz, CDCl3): δ 167.5
t
CDCl3): δ 7.48−7.42 (m, 1 H, Ar), 7.18−7.12 (m, 1 H, Ar), 7.10−
7.04 (m, 2 H, Ar), 4.36 (br, 1 H, NH), 2.95 (s, 6 H, Me), 2.77−2.74
(m, 2 H, CH2), 2.63 (s, 6 H, Me), 2.63−2.61 (m, 2 H, CH2). 13C{1H}
APT NMR (75.5 MHz, CDCl3): δ 181.8 (CO), 146.4, 144.4 (C, Ar),
129.7, 128.7, 127.4, 124.3 (CH, Ar), 63.5, 58.5 (CH2), 51.0, 48.8
(Me).
3b·H2O. Yield: 57%. Anal. Calcd for C14H25N3O2Pd: C, 44.99; H,
6.74; N, 11.24. Found: C, 45.02; H, 6.60; N, 11.25. Mp: 92−93 °C
(dec). IR (Nujol, cm−1): ν(OH), 3399; ν(CO), 1589. 1H NMR (300.1
MHz, CDCl3): δ 7.48 (dd, 4JHH = 1.8 Hz, 3JHH = 6.9 Hz, 1 H, Ar), 7.12
(m, 1 H, Ar), 7.07−6.96 (m, 2 H, Ar), 3.02 (s, 3 H, Me, benzamide),
2.92 (s, 6 H, Me, tmeda), 2.72 (m, 8 H, CH2 + Me, tmeda), 2.61 (br, 2
H, CH2, tmeda), 2.15 (s, 2 H, H2O). 13C{1H} APT NMR (75.5 MHz,
CDCl3): δ 180.2 (CO), 146.0, 145.1 (C, Ar), 129.0, 127.6, 127.0,
124.4 (CH, Ar), 63.7, 60.3 (CH2), 51.1, 48.8 (Me, tmeda), 34.8 (Me,
benzamide).
(CO), 147.3 (CN), 134.4 (C3a), 131.8 (C6), 130.9 (C5), 129.0
(C7a), 127.0 (C7), 123.1 (C4), 53.6 (CMe3), 30.8 (CMe3), 25.2
(NMe).
Synthesis of trans-[Pd{C(NXy)C6H4C(O)NMe2-2}I(CNXy)2]
(6). To a solution of 1c (132 mg, 0.27 mmol) in CH2Cl2 (10 mL)
was added XyNC (105 mg, 0.80 mmol), and the mixture was stirred
for 30 min. Partial evaporation of the solvent (3 mL) and addition of
n-pentane (15 mL) led to the precipitation of a yellow solid, which was
filtered off, washed with n-pentane (5 × 3 mL), and vacuum-dried to
give 6. Yield: 173 mg, 84%. Anal. Calcd for C36H37IN4OPd: C, 55.79;
H, 4.81; N, 7.23. Found: C, 55.89; H, 4.70; N, 7.21. Mp: 154−155 °C
(dec). IR (Nujol, cm−1): ν(CN), 2184; ν(CO), 1623; ν(CN),
1584. 1H NMR (400.9 MHz, CDCl3): δ 8.07 (dd, 4JHH = 1.2 Hz, 3JHH
4
3
= 7.6 Hz, 1 H, Ar), 7.45 (td, JHH = 1.2 Hz, JHH = 7.6 Hz, 1 H, Ar),
4
3
4
7.37 (td, JHH = 1.2 Hz, JHH = 7.6 Hz, 1 H, Ar), 7.26 (dd, JHH = 1.2
Hz, 3JHH = 7.6 Hz, 1 H, Ar), 7.20 (t, 3JHH = 7.6 Hz, 2 H, p-H, XyNCc),
7.04 (m, 4 H, m-H, XyNCc), 6.85 (t, 3JHH = 7.6 Hz, 1 H, p-H, XyNCi),
6.90−6.60 (br, 2 H, m-H, XyNCi), 3.08 (s, 3 H, Me, benzamide),
3.075 (s, 3 H, Me, benzamide), 2.24 (s, 12 H, Me, XyNCc), 2.40−2.00
(br, 6 H, Me, XyNCi). 13C{1H} APT NMR (75.5 MHz, CDCl3): δ
175.8 (CN), 171.2 (CO), 150.2 (i-C, XyNCi), 143.9 (C, Ar), 136.0
(C, Ar + o-C, XyNCc), 129.85 (CH, XyNCc), 129.76, 128.4, 128.3
(CH, Ar), 128.2 (CH, XyNCi), 127.9 (CH, XyNCc), 127.1 (o-C,
XyNCi), 126.1 (CH, Ar), 123.3 (CH, XyNCi), 39.7, 34.6 (NMe), 18.8
(Me, XyNC); CN and i-C of XyNCc not observed.
Synthesis of Isoindoline-1,3-dione (Phthalimide) (4a). A
solution of 2a (130 mg, 0.26 mmol) in acetone (15 mL) was stirred
under a CO atmosphere (1.4 bar) for 3 h. A black precipitate of Pd
gradually formed. The solvent was removed under reduced pressure,
and the residue was chromatographed on silica gel, using a 2:1 EtOAc/
Et2O mixture as the eluent. Compound 4a was obtained as a colorless
solid after evaporation of the solvents. Yield: 32 mg, 82%. Mp: 235 °C
39
1
(lit. 237−238 °C ). The H NMR data are in agreement with those
reported in the literature.40
Synthesis of 2-Methylisoindoline-1,3-dione (N-Methyl-
phthalimide) (4b). A solution of 2b (139 mg, 0.27 mmol) in
acetone (15 mL) was stirred under a CO atmosphere (1.4 bar) for 3 h.
A black precipitate of Pd gradually formed. The solvent was
evaporated under reduced pressure, and the residue was extracted
with Et2O (6 × 5 mL). The combined extracts were filtered through
anhydrous MgSO4, and the filtrate was evaporated to dryness to give
4b as a colorless solid. Yield: 35 mg, 79%. Mp: 134 °C (lit. 134 °C41).
The 1H NMR data are in agreement with those reported in the
literature.41,42
Synthesis of 3-(2,6-Dimethylphenylimino)-2-methylisoindo-
lin-1-one (5b). Method A: To a solution of 1b (100 mg, 0.21 mmol)
in CH2Cl2 (10 mL) was added XyNC (27.1 mg, 0.21 mmol), and the
mixture was stirred for 6 h. A black suspension was obtained. The
solvent was removed under vacuum, the residue was extracted with n-
hexane (8 × 5 mL), and the combined extracts were filtered through
anhydrous MgSO4. Compound 5b was obtained as a yellow solid after
evaporation of the solvent. Yield: 46 mg, 84%. Method B: To a
solution of 2b (127 mg, 0.25 mmol) in acetone (15 mL) was added
XyNC (66 mg, 0.50 mmol). The mixture was stirred for 6 h, and the
solvent was removed under vacuum. Compound 5b was isolated as
described for method A. Yield: 60 mg, 90%. Anal. Calcd for
C17H16N2O: C, 77.25; H, 6.10; N, 10.60. Found: C, 76.92; H, 5.92;
N, 10.51. Mp: 92−94 °C. IR (Nujol, cm−1): ν(CO), 1743; ν(CN),
1669. HRMS (ESI+, m/z): exact mass calcd for C17H17N2O [M + H]+
requires 265.1335, found 265.1344, error = 3.08 ppm. 1H NMR (400.9
Synthesis of [Pd{κ2C,O-C(X)C(X′)C6H4C(O)NRR′-2}(tmeda)]-
TfO [NRR′ = NH2 and X = Ph, X′ = Me (7a); NRR′ = NHMe and X
= Ph, X′ = Me (7b), X = X′ = Ph (8b), Et (9b), CO2Me (10b), X =
CO2Me, X′ = Ph (11b), X = CO2Et, X′ = Ph (12b); NRR′ = NMe2
and X = X′ = Ph (8c), Et (9c)]. A solution of the appropriate complex
2 (0.47 mmol) and the alkyne (4.70 mmol for NH2 and NHMe
derivatives; 2.35 mmol for NMe2 derivatives) in a 1:2 acetone/CH2Cl2
mixture (15 mL) (7a) or CH2Cl2 (10 mL) (other complexes) was
stirred for 64 h (7a), 24 h (7b, 9b, 10b, 8c, 9c), 48 h (11b, 12b), or 5
d (8b). The mixture was filtered through anhydrous MgSO4, and the
filtrate was concentrated to ca. 4 mL (11b, 12b) or 1 mL (other
complexes). The addition of Et2O (20 mL) led to the precipitation of
a yellow solid, which was filtered off, washed with Et2O (3 × 3 mL),
recrystallized from CH2Cl2/Et2O, and vacuum-dried to give the
corresponding complex 7−12.
7a. Yield: 65%. Anal. Calcd for C23H30F3N3O4PdS: C, 45.44; H,
4.97; N, 6.91; S, 5.27. Found: C, 45.37; H, 4.89; N, 6,79; S, 5.27. Mp:
146−147 °C (dec). IR (Nujol, cm−1): ν(NH), 3330, 3197; ν(CO),
1
1662. H NMR (400.9 MHz, CDCl3): δ 7.89 (br s, 1 H, NH), 7.66
(m, 1 H, Ar), 7.58 (td, 4JHH = 1.6 Hz, 3JHH = 7.6 Hz, 1 H, Ar), 7.51−
7.47 (m, 3 H, Ar + Ph), 7.39−7.33 (m, 3 H, Ar + Ph), 7.26−7.23 (m, 2
H, NH + Ph), 2.65−2.50 (m, 5 H, CH2 + NMe), 2.34 (s, 3 H, NMe),
2.27−2.18 (m, 2 H, CH2), 2.10 (s, 3 H, NMe), 2.08 (s, 3 H, CMe),
1.83 (s, 3 H, NMe). 13C{1H} APT NMR (100.8 MHz, CDCl3): δ
178.8 (CO), 144.8 (PdC), 143.4 (C, Ar), 142.5 (C, Ph), 133.3 (C,
4672
dx.doi.org/10.1021/om4006406 | Organometallics 2013, 32, 4664−4676

Organometallics
Article
Ar), 131.7, 129.2 (CH, Ar), 128.5 (CMe), 128.4, 128.3 (CH, Ph),
127.2, 126.4 (CH, Ar), 125.9 (CH, Ph), 63.7, 57.1 (CH2), 52.8, 48.9,
48.8, 45.9 (NMe), 20.7 (CMe).
benzamide), 2.73−2.64 (m, 1 H, CH2CH3), 2.63−2.61 (m, 1 H, CH2,
tmeda), 2.61 (s, 3 H, Me, tmeda), 2.51 (s, 3 H, Me, tmeda), 2.58−2.48
(m, 2 H, CH2, tmeda), 2.31 (s, 3 H, Me, tmeda), 2.34−2.21 (m, 2 H,
CH2, tmeda, + CH2CH3), 2.14−2.04 (m, 1 H, CH2CH3), 2.04 (s, 3 H,
7b. Yield: 76%. Anal. Calcd for C24H32F3N3O4PdS: C, 46.34; H,
3
Me, tmeda), 1.96−1.87 (m, 1 H, CH2CH3), 1.25 (t, JHH = 7.6 Hz, 3
5.19; N, 6.76; S, 5.16. Found: C, 46.10; H, 5.27; N, 6.71; S, 5.10. Mp:
3
H, CH2CH3), 0.73 (t, JHH = 7.6 Hz, 3 H, CH2CH3). 13C{1H} APT
1
80−82 °C. IR (Nujol, cm−1): ν(NH), 3280; ν(CO), 1600. H NMR
(400.9 MHz, CDCl3): δ 8.50 (br q, 3JHH = 4.8 Hz, 1 H, NH), 7.60 (dd,
NMR (100.8 MHz, CDCl3): δ 176.4 (CO), 152.0 (PdC), 142.7, 135.8
(C, Ar), 133.4 (PdCC), 130.5, 128.6, 125.9, 125.5 (CH, Ar), 63.6,
56.9 (CH2, tmeda), 52.2, 51.2, 47.5, 47.1 (Me, tmeda), 41.3, 36.3 (Me,
benzamide), 26.4, 25.7 (CH2CH3), 15.6, 14.7 (CH2CH3).
4JHH = 0.8 Hz, 3JHH = 7.6 Hz, 1 H, Ar), 7.53 (td, 4JHH = 1.2 Hz, 3JHH
=
7.6 Hz, 1 H, Ar), 7.48−7.44 (m, 3 H, Ar + Ph), 7.36−7.31 (m, 3 H, Ar
3
+ Ph), 7.27−7.23 (m, 1 H, Ph), 3.00 (d, JHH = 4.8 Hz, 3 H, Me,
10b. Yield: 96%. Anal. Calcd for C21H30F3N3O8PdS: C, 38.93; H,
4.67; N, 6.48; S, 4.95. Found: C, 39.09; H, 4.94; N, 6.34; S, 4.54. Mp:
149−151 °C. IR (Nujol, cm−1): ν(NH), 3333; ν(COO), 1695;
ν(CO), 1618. 1H NMR (400.9 MHz, CDCl3): δ 8.65 (br q, 3JHH = 4.8
benzamide), 2.62−2.51 (m, 5 H, CH2 + Me, tmeda), 2.34 (s, 3 H, Me,
tmeda), 2.29−2.21 (m, 2 H, CH2), 2.07 (s, 3 H, Me, tmeda), 2.06 (s, 3
H, CMe), 1.84 (s, 3 H, Me, tmeda). 13C{1H} APT NMR (100.8 MHz,
CDCl3): δ 176.4 (CO), 144.5 (PdC), 143.3 (C, Ar), 142.7 (C, Ph),
134.1 (C, Ar), 131.2, 128.8 (CH, Ar), 128.7 (CMe), 128.3, 128.2 (CH,
Ph), 127.5, 126.4 (CH, Ar), 125.8 (CH, Ph), 63.6, 57.1 (CH2), 52.7,
48.9, 48.8, 46.0 (Me, tmeda), 28.1 (Me, benzamide), 20.6 (CMe).
8b·H2O. Yield: 74%. Anal. Calcd for C29H36F3N3O5PdS: C, 49.61;
H, 5.17; N, 5.98; S, 4.57. Found: C, 49.21; H, 5.13; N, 6.14; S, 4.73.
Mp: 178−180 °C (dec). IR (Nujol, cm−1): ν(NH), 3273; ν(CO),
4
3
Hz, 1 H, NH), 7.70 (m, 1 H, Ar), 7.59 (td, JHH = 1.2 Hz, JHH = 7.6
Hz, 1 H, Ar), 7.50−7.45 (m, 2 H, Ar), 3.87 (s, 3 H, CO2Me), 3.65 (s,
3 H, CO2Me), 2.99 (d, 3JHH = 4.8 Hz, 3 H, Me, benzamide), 2.75 (s, 3
H, Me, tmeda), 2.81−2.73 (m, 2 H, CH2, tmeda), 2.553 (s, 3 H, Me,
tmeda), 2.549 (s, 3 H, Me, tmeda), 2.37−2.30 (m, 2 H, CH2), 2.13 (s,
3 H, Me, tmeda). 13C{1H} APT NMR (100.8 MHz, CDCl3): δ 175.7
(CONHMe), 171.4 (CO2Me), 164.0 (PdC), 161.5 (CO2Me), 136.1,
134.4 (C, Ar), 131.3, 131.1 (CH, Ar), 129.3 (PdCC), 127.94,
127.91 (CH, Ar), 64.6, 58.1 (CH2), 54.4 (Me, tmeda), 52.2, 52.0
(CO2Me), 49.7, 48.2, 46.4 (Me, tmeda), 28.3 (NHMe).
1
3
1600. H NMR (400.9 MHz, CDCl3): δ 8.51 (br q, JHH = 4.8 Hz, 1
4
3
H, NH), 7.64 (dd, JHH = 1.2 Hz, JHH = 7.6 Hz, 1 H, Ar), 7.53 (dd,
4JHH = 1.2 Hz, 3JHH = 7.6 Hz, 1 H, Ar), 7.48 (td, 4JHH = 1.2 Hz, 3JHH
=
7.6 Hz, 1 H, Ar), 7.35−7.30 (m, 3 H, Ar + Ph), 7.18−7.07 (m, 5 H,
11b. Yield: 71%. Anal. Calcd for C25H32F3N3O6PdS: C, 45.08; H,
4.84; N, 6.31; S, 4.81. Found: C, 44.67; H, 4.66; N, 6.22; S, 4.51. Mp:
175−177 °C (dec). IR (Nujol, cm−1): ν(NH), 3233; ν(COO), 1693;
ν(CO), 1600. 1H NMR (400.9 MHz, CDCl3): δ 9.04 (br q, 3JHH = 4.8
Hz, 1 H, NH), 7.72 (m, 1 H, Ar), 7.48−7.40 (m, 2 H, Ar), 7.25−7.14
(m, 4 H, Ar + Ph), 7.03−7.00 (m, 2 H, Ph), 3.49 (CO2Me), 3.03 (d,
3JHH = 4.8 Hz, 3 H, Me, benzamide), 2.88 (s, 3 H, Me, tmeda), 2.81−
2.79 (m, 2 H, CH2), 2.70 (s, 3 H, Me, tmeda), 2.58 (s, 3 H, Me,
tmeda), 2.35−2.29 (m, 2 H, CH2), 2.16 (s, 3 H, Me, tmeda). 13C{1H}
APT NMR (75.5 MHz, CDCl3): δ 176.3 (CONHMe), 171.5
(CO2Me), 141.6 (C, Ar), 140.6 (C, Ph), 140.4 (PdCC), 138.2
(PdC), 134.6 (C, Ar), 131.4, 130.9 (CH, Ar), 128.5, 128.1 (CH, Ph),
127.7, 127.6 (CH, Ar), 127.3 (CH, Ph), 64.5, 57.9 (CH2), 54.4 (Me,
tmeda), 51.8 (CO2Me), 49.9, 48.2, 46.6, 28.4 (NHMe).
3
Ph), 7.04−6.98 (m, 3 H, Ph), 3.07 (d, JHH = 4.8 Hz, 3 H, Me,
benzamide), 2.64−2.53 (m, 2 H, CH2), 2.53 (s, 3 H, Me, tmeda), 2.50
(s, 3 H, Me, tmeda), 2.34−2.21 (m, 2 H, CH2), 2.07 (s, 3 H, Me,
tmeda), 2.00 (s, 3 H, Me, tmeda), 1.68 (s, 2 H, H2O). 13C{1H} APT
NMR (75.5 MHz, CDCl3): δ 176.6 (CO), 151.6 (PdC), 142.6 (C,
Ph), 141.6 (C, Ar), 140.5 (C, Ph), 135.4 (PdCC), 135.3 (C, Ar),
131.2, 130.0 (CH, Ar), 129.4, 128.1, 128.0, 127.9 (CH, Ph), 127.3,
126.7 (CH, Ar), 126.2, 125.8 (CH, Ph), 63.7, 57.2 (CH2), 53.0, 49.01,
48.95, 46.2 (Me, tmeda), 28.2 (Me, benzamide).
8c. Yield: 88%. Anal. Calcd for C30H36F3N3O4PdS: C, 51.61; H,
5.20; N, 6.02; S, 4.59. Found: C, 51.52; H, 5.19; N, 5.93; S, 5.06. Mp:
1
210−212 °C (dec). IR (Nujol, cm−1): ν(CO), 1587. H NMR (400.9
MHz, CDCl3): δ 7.73 (m, 1 H, Ar), 7.61 (td, 4JHH = 1.6 Hz, 3JHH = 7.6
Hz, 1 H, Ar), 7.49−7.41 (m, 2 H, Ar), 7.34−7.32 (m, 2 H, Ph), 7.18−
7.05 (m, 6 H, Ph), 7.00−6.98 (m, 2 H, Ph), 3.29 (s, 3 H, Me,
benzamide), 2.93 (s, 3 H, Me, benzamide), 2.76−2.62 (m, 2 H, CH2),
2.59 (s, 3 H, Me, tmeda), 2.48 (s, 3 H, Me, tmeda), 2.42−2.32 (m, 2
H, CH2), 2.14 (s, 3 H, Me, tmeda), 1.95 (s, 3 H, Me, tmeda). 13C{1H}
APT NMR (100.8 MHz, CDCl3): δ 176.6 (CO), 152.9 (PdC), 142.5
(C, Ph), 142.3 (C, Ar), 140.3 (C, Ph), 135.2 (C, Ar), 135.1 (PdC
C), 130.8, 129.7 (CH, Ar), 128.8, 128.2, 128.1, 128.0 (CH, Ph), 126.6
(CH, Ar), 126.3, 125.9 (CH, Ph), 125.7 (CH, Ar), 64.0, 57.4 (CH2),
53.1, 49.1, 49.0, 46.2 (Me, tmeda), 41.5, 36.6 (Me, benzamide).
9b. Yield: 53%. Anal. Calcd for C21H34F3N3O4PdS: C, 42.90; H,
5.83; N, 7.15; S, 5.45. Found: C, 42.57; H, 5.81; N, 7.04; S, 5.39. Mp:
127−129 °C (dec). IR (Nujol, cm−1): ν(NH), 3237; ν(CO), 1608. 1H
12b. Yield: 67%. Anal. Calcd for C26H34F3N3O6PdS: C, 45.92; H,
5.04; N, 6.18; S, 4.72. Found: C, 45.93; H, 5.15; N, 6.18; S, 4.63. Mp:
199−200 °C (dec). IR (Nujol, cm−1): ν(NH), 3240; ν(COO), 1690;
ν(CO), 1604. 1H NMR (400.9 MHz, CDCl3): δ 9.01 (br q, 3JHH = 4.8
Hz, 1 H, NH), 7.63 (dd, 4JHH = 1.2 Hz, 3JHH = 7.6 Hz, 1 H, Ar), 7.44
4
3
4
(td, JHH = 1.2 Hz, JHH = 7.6 Hz, 1 H, Ar), 7.38 (dd, JHH = 1.2 Hz,
3JHH = 7.6 Hz, 1 H, Ar), 7.22−7.14 (m, 4 H, Ar + Ph), 7.02−6.99 (m,
2 H, Ph), 4.06, 3.89 (AB part of ABX3 system, 2JHH = 10.8 Hz, 3JHH
=
6.8 Hz, 2 H, CH2CH3), 3.00 (d, 3JHH = 4.8 Hz, 3 H, Me, benzamide),
2.88 (s, 3 H, Me, tmeda), 2.81−2.78 (m, 2 H, CH2, tmeda), 2.68 (s, 3
H, Me, tmeda), 2.56 (s, 3 H, Me, tmeda), 2.38−2.30 (m, 2 H, CH2,
3
tmeda), 2.13 (s, 3 H, Me, tmeda), 0.89 (t, JHH = 6.8 Hz, 3 H,
CH2CH3). 13C{1H} APT NMR (100.8 MHz, CDCl3): δ 176.4
(CONHMe), 171.0 (CO2Et), 141.6 (C, Ar), 140.5 (PdCC + C, Ph),
138.9 (PdC), 134.5 (C, Ar), 131.3, 130.9 (CH, Ar), 128.7, 127.9 (CH,
Ph), 127.6, 127.5 (CH, Ar), 127.2 (CH, Ph), 64.5 (CH2, tmeda), 60.4
(CH2CH3), 57.9 (CH2, tmeda), 54.4, 49.8, 48.2, 46.5 (Me, tmeda),
28.3 (NHMe), 13.7 (CH2CH3).
3
NMR (400.9 MHz, CDCl3): δ 8.34 (br q, JHH = 4.8 Hz, 1 H, NH),
4
4
7.50 (dd, JHH = 1.2 Hz, 3JHH = 7.6 Hz, 1 H, Ar), 7.47 (td, JHH = 1.2
Hz, 3JHH = 7.6 Hz, 1 H, Ar), 7.34 (m, 1 H, Ar), 7.28 (td, 4JHH = 1.2 Hz,
3JHH = 7.6 Hz, 1 H, Ar), 2.93 (d, 3JHH = 4.8 Hz, 3 H, NHMe), 2.62 (s,
3 H, Me, tmeda), 2.50 (s, 3 H, Me, tmeda), 2.64−2.45 (m, 4 H, CH2,
tmeda), 2.34 (s, 3 H, Me, tmeda), 2.30−2.17 (m, 2 H, CH2CH3),
2.13−2.04 (m, 1 H, CH2CH33), 2.04 (s, 3 H, Me, tmeda), 2.02−1.88
(m, 1 H, CH2CH3), 1.29 (t, JHH = 7.6 Hz, 3 H, CH2CH3), 0.70 (t,
3JHH = 7.6 Hz, 3 H, CH2CH3). 13C{1H} APT NMR (100.8 MHz,
CDCl3): δ 176.7 (CO), 150.2 (PdC), 141.9, 136.7 (C, Ar), 133.5
(PdCC), 130.8, 128.3, 126.6, 126.0 (CH, Ar), 63.4, 56.8 (CH2),
52.2, 51.2, 47.5, 47.0 (Me, tmeda), 27.9 (NHMe), 26.5, 26.3
(CH2CH3), 15.5, 14.4 (CH2CH3).
Synthesis of 3,4-Diethylisoquinolin-1(2H)-one (13). A mixture
of 2a (122 mg, 0.25 mmol) and 3-hexyne (285 μL, 2.50 mmol) in
acetone (20 mL) was stirred at 40 °C for 24 h. The solvent was
evaporated under vacuum, the residue was extracted with Et2O (6 × 5
mL), and the combined extracts were filtered through anhydrous
MgSO4. The pale yellow filtrate was evaporated to dryness, and the
residue was stirred in n-pentane (10 mL) for 16 h, whereupon a
colorless precipitate formed, which was filtered off and vacuum-dried
to give 13. Yield: 15 mg, 30%. HRMS (ESI+, m/z): exact mass calcd
for C13H16NO [M + H]+ requires 202.1226, found 202.1233, error =
3.41 ppm. Mp: 180 °C (lit. 173−175 °C21). The 1H NMR data are in
agreement with those reported in the literature.21
9c. Yield: 87%. Anal. Calcd for C22H36F3N3O4PdS: C, 43.89; H,
6.03; N, 6.98; S, 5.33. Found: C, 43.83; H, 6.06; N, 6.99; S, 5.34. Mp:
1
137−138 °C (dec). IR (Nujol, cm−1): ν(CO), 1587. H NMR (400.9
MHz, CDCl3): δ 7.53 (m, 1 H, Ar), 7.42 (m, 1 H, Ar), 7.36 (td, 4JHH
1.2 Hz, JHH = 7.6 Hz, 1 H, Ar), 7.31 (dd, JHH = 1.2 Hz, JHH = 7.6
=
3
4
3
Synthesis of (Z)-5-Methyl-4-phenyl-2H-benzo[c]azepine-1,3-
dione (14a), (Z)-2,5-Dimethyl-4-phenyl-2H-benzo[c]azepine-
Hz, 1 H, Ar), 3.13 (s, 3 H, Me, benzamide), 3.00 (s, 3 H, Me,
4673
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Organometallics
Article
1,3-dione (14b), (Z)-2-Methyl-4,5-diphenyl-2H-benzo[c]-
azepine-1,3-dione (14c), and (Z)-4,5-Diethyl-2-methyl-2H-
benzo[c]azepine-1,3-dione (14d). A solution of complex 7a, 7b,
8b, or 9b (0.45 mmol) in CHCl3 (15 mL) was stirred under a CO
atmosphere (1.4 bar) for 3 h (7a) or 24 h (7−9b), whereupon a black
precipitate of Pd gradually formed. The suspension was filtered
through anhydrous MgSO4, and the solvent was removed under
reduced pressure. The residue was chromatographed on silica gel,
using as the eluent Et2O [Rf = 0.8−0.9 (14a), 0.9 (14d)], a 1:1
EtOAc/n-hexane mixture [Rf = 0.8−0.9 (14b)], or a 2:1 Et2O/n-
hexane mixture [Rf = 0.7−0.8 (14c)]. The compounds were isolated as
colorless solids (14a−c) or as a yellow oil (14d) after evaporation of
the solvents.
14a. Yield: 81%. Anal. Calcd for C17H13NO2: C, 77.55; H, 4.98; N,
5.32. Found: C, 77.64; H, 4.90; N, 5.34. Mp: 200−202 °C. IR (Nujol,
cm−1): ν(CO), 1688, 1655. HRMS (ESI+, m/z): exact mass calcd for
C17H14NO2 [M + H]+ requires 264.1019, found 264.1025, error = 2.29
ppm. 1H NMR (400.9 MHz, CDCl3): δ 8.64 (br, 1 H, H2), 8.20 (m, 1
H, H9), 7.72 (m, 1 H, H6), 7.67 (m, 1 H, H7), 7.55 (m, 1 H, H8),
7.46−7.41 (m, 2 H, Ph), 7.39−7.35 (m, 1 H, Ph), 7.25−7.22 (m, 2 H,
Ph), 2.18 (s, 3 H, Me). 13C{1H} APT NMR (75.5 MHz, CDCl3): δ
166.7 (C1), 166.5 (C3), 142.4 (C5), 139.1 (C, Ph), 136.7 (C5a),
136.6 (C4), 132.8 (C7), 131.7 (C9), 131.3 (C9a), 129.4 (C8), 129.0
(CH, Ph), 128.7 (C6), 128.6, 127.9 (CH, Ph), 23.7 (Me).
4.23. IR (Nujol, cm−1): ν(CO), 1759, 1739, 1687. HRMS (ESI+, m/
z): exact mass calcd for C20H20NO5 [M + H]+ requires 354.1336,
1
found 354.1343, error = 2.07 ppm. H NMR (400.9 MHz, CDCl3): δ
7.85 (m, 1 H, H7), 7.79 (m, 1 H, H4), 7.55 (td, 4JHH = 1.2 Hz, 3JHH
=
4
3
7.2 Hz, 1 H, H5), 7.49 (td, JHH = 1.2 Hz, JHH = 7.6 Hz, 1 H, H6),
7.33−7.29 (m, 3 H, Ph), 7.06−7.03 (m, 2 H, Ph), 4.86 (s, 1 H,
CHCO2Me), 3.64 (s, 3 H, CO2Me), 3.48 (s, 3 H, CO2Me), 2.97 (s, 3
H, NMe). 13C{1H} APT NMR (75.5 MHz, CDCl3): δ 168.0 (C1),
166.6, 166.3 (CO2Me), 146.6 (C3a), 138.0 (C, Ph), 131.9 (C5), 131.8
(C7a), 128.92 (C6), 128.87 (CH, Ph), 128.4, 125.9 (CH, Ph), 125.0
(C4), 123.1 (C7), 70.4 (C3), 55.6 (CHCO2Me), 52.79, 52.77
(CO2Me), 25.6 (NMe).
Synthesis of 3-[Ethoxycarbonyl(methoxycarbonyl)methyl]-
2-methyl-3-phenylisoindolin-1-one (15c). This compound was
obtained as a colorless oil using the method described for 15b, either
from 11b (160 mg, 0.24 mmol) and EtOH (29 μL, 0.50 mmol) or
from 12b (161 mg, 0.24 mmol) and MeOH (20 μL, 0.49 mmol), and
purified by column chromatography using Et2O as the eluent (Rf =
0.60−0.70). An approximately 1:1 mixture of the two diastereomeric
pairs of enantiomers was obtained. Yield: 97%. Anal. Calcd for
C21H21NO5: C, 68.65; H, 5.76; N, 3.81. Found: C, 68.43; H, 5.76; N,
3.74. IR (CH2Cl2, cm−1): ν(CO), 1760, 1736, 1696. HRMS (ESI+, m/
z): exact mass calcd for C21H22NO5 [M + H]+ requires 368.1492,
1
found 368.1506, error = 3.74 ppm. H NMR (400.9 MHz, CDCl3): δ
14b. Yield: 83%. Anal. Calcd for C18H15NO2: C, 77.96; H, 5.45; N,
5.05. Found: C, 78.03; H, 5.57; N, 4.98. Mp: 98−99 °C. IR (Nujol,
cm−1): ν(CO), 1687, 1649. HRMS (ESI+, m/z): exact mass calcd for
C18H16NO2 [M + H]+ requires 278.1176, found 278.1184, error = 2.89
ppm. 1H NMR (400.9 MHz, CDCl3): δ 7.91 (m, 1 H, H9), 7.59 (m, 2
H, H7 + H6), 7.50−7.46 (m, 1 H, H8), 7.44−7.34 (m, 3 H, Ph),
7.28−7.26 (m, 2 H, Ph), 3.44 (s, 3 H, NMe), 2.10 (s, 3 H, CMe).
13C{1H} APT NMR (100.8 MHz, CDCl3): δ 170.9 (C1), 170.7 (C3),
7.86−7.83 (m, 3 H, H4, H7), 7.74 (m, 1 H, H4), 7.55−7.47 (m, 4 H,
H5, H6), 7.32−7.28 (m, 6 H, Ph), 7.08−7.02 (m, 4 H, Ph), 4.85 (s, 1
H, CHCOO), 4.84 (s, 1 H, CHCOO), 4.08−4.05 (m, 2 H, CH2CH3),
3.95−3.89 (m, 2 H, CH2CH3), 3.65 (s, 3 H, CO2Me), 3.50 (s, 3 H,
CO2Me), 3.02 (s, 3 H, NMe), 2.95 (s, 3 H, NMe), 1.08 (t, 3JHH = 7.2
3
Hz, 3 H, CH2CH3), 0.98 (t, JHH = 7.2 Hz, 3 H, CH2CH3). 13C{1H}
APT NMR (100.8 MHz, CDCl3): δ 168.2, 167.9 (C1), 166.8, 166.5
(CO2Me), 166.1, 165.8 (CO2Et), 147.0, 146.5 (C3a), 138.2, 138.0 (C,
Ph), 132.1 (C7a), 131.9 (C5), 131.6 (C7a), 128.93 (C6), 128.90 (CH,
Ph), 128.81 (C6), 128.80, 128.4, 128.3, 126.0, 125.7 (CH, Ph), 125.3,
124.6 (C4), 123.2, 123.1 (C7), 70.5, 70.4 (C3), 62.0, 61.9 (CH2CH3),
56.2, 55.6 (CHCOO), 52.72, 52.71 (CO2Me), 26.0, 25.4 (NMe), 13.7,
13.6 (CH2CH3).
139.2 (C4), 138.0 (C5), 137.4 (C, Ph), 136.0 (C5a), 134.1 (C9a),
131.6 (C7), 131.0 (C9), 129.1 (CH, Ph), 128.9 (C8), 128.5, 127.8
(CH, Ph), 127.1 (C6), 33.6 (NMe), 21.2 (CMe).
14c. Yield: 76%. Anal. Calcd for C23H17NO2: C, 81.40; H, 5.05; N,
4.13. Found: C, 81.25; H, 4.81; N, 4.19. Mp: 151−153 °C. IR (Nujol,
cm−1): ν(CO), 1689, 1645. HRMS (ESI+, m/z): exact mass calcd for
C23H18NO2 [M + H]+ requires 340.1332, found 340.1338, error = 1.74
Synthesis of 3-[Di(ethoxycarbonyl)methyl]-2-methyl-3-phe-
nylisoindolin-1-one (15d). This compound was obtained as a
colorless oil using the method described for 15b, from 12b (192 mg,
0.28 mmol) and EtOH (33 μL, 0.56 mmol), and purified by column
chromatography using Et2O as the eluent (Rf = 0.70). Yield: 107 mg,
99%. Anal. Calcd for C22H23NO5: C, 69.28; H, 6.08; N, 3.67. Found:
C, 69.13; H, 5.94; N, 3.78. IR (CH2Cl2, cm−1): ν(CO), 1757, 1733,
1696. HRMS (ESI+, m/z): exact mass calcd for C22H24NO5 [M + H]+
requires 382.1649, found 382.1661, error = 3.2 ppm. 1H NMR (400.9
MHz, CDCl3): δ 7.85 (m, 1 H, H7), 7.82 (m, 1 H, H4), 7.54 (td, 4JHH
= 1.6 Hz, 3JHH = 7.6 Hz, 1 H, H5), 7.48 (td, 4JHH = 1.2 Hz, 3JHH = 7.6
Hz, 1 H, H6), 7.33−7.28 (m, 3 H, Ph), 7.07−7.04 (m, 2 H, Ph), 4.83
(s, 1 H, CHCOO), 4.09 (m, 2 H, CH2CH3), 3.94 (m, 2 H, CH2CH3),
1
ppm. H NMR (400.9 MHz, CDCl3): δ 7.96 (m, 1 H, H9), 7.45 (td,
4JHH = 1.2 Hz, 3JHH = 7.2 Hz, 1 H, H8), 7.37 (td, 4JHH = 1.6 Hz, 3JHH
=
7.2 Hz, 1 H, H7), 7.29−7.27 (m, 2 H, Ph), 7.15−7.11 (m, 6 H, Ph),
6.97−6.94 (m, 3 H, Ph + H6), 3.44 (s, 3 H, Me). 13C{1H} NMR
(100.8 MHz, CDCl3): δ 170.86, 170.84 (CO), 142.5 (C5), 139.6,
137.2 (C, Ph), 136.3 (C4), 135.7 (C5a), 134.7 (C9a), 131.1 (C7),
130.8 (C9), 130.6 (CH, Ph + C6), 129.2 (C8), 127.9, 127.50, 127.45,
127.3 (CH, Ph), 33.9 (Me).
14d·0.25H2O. Yield: 79%. Anal. Calcd for C15H17.5NO2.25: C, 72.70;
H, 7.12; N, 5.65. Found: C, 72.84; H, 6.92; N, 5.49. IR (Nujol, cm−1):
ν(CO), 1700, 1662. HRMS (ESI+, m/z): exact mass calcd for
C15H181NO2 [M + H]+ requires 244.1332, found 244.1341, error = 3.71
ppm. H NMR (400.9 MHz, CDCl3): δ 7.81−7.79 (m, 1 H, H9),
7.53−7.50 (m, 2 H, H6, H7), 7.43−7.37 (m, 1 H, H8), 3.41 (NMe),
2.70 (q, 3JHH = 7.6 Hz, 2 H, CH2), 2.63 (q, 3JHH = 7.6 Hz, 2 H, CH2),
1.62 (br, 0.5 H, H2O), 1.12 (t, 3JHH = 7.6 Hz, 3 H, CH2CH3), 1.05 (t,
3JHH = 7.6 Hz, 3 H, CH2CH3). 13C{1H} APT NMR (75.5 MHz,
3
3.00 (s, 3 H, NMe), 1.11 (t, JHH = 7.2 Hz, 3 H, CH2CH3), 1.00 (t,
3JHH = 7.2 Hz, 3 H, CH2CH3). 13C{1H} APT NMR (100.8 MHz,
CDCl3): δ 168.0 (C1), 166.2, 165.9 (CO2Et), 146.8 (C3a), 138.3 (C,
Ph), 131.92 (C7a), 131.86 (C5), 128.8 (C6 + CH, Ph), 128.3, 125.9
(CH, Ph), 125.0 (C4), 123.1 (C7), 70.4 (C3), 61.85, 61.77
(CH2CH3), 56.1 (CHCO2Et), 25.7 (NMe), 13.8, 13.6 (CH2CH3).
Synthesis of 3-(Methoxycarbonylmethyl)-2-methyl-3-phe-
nylisoindolin-1-one (16). A solution of 11b (118 mg, 0.18 mmol)
in CHCl3 (15 mL) was stirred under a CO atmosphere (1.4 bar) at
room temperature for 6 h and then at 50 °C for 24 h. The resulting
black suspension was filtered through anhydrous MgSO4, and the
filtrate was concentrated to dryness. The residue was chromato-
graphed on silica gel, using Et2O as the eluent [Rf = 0.4−0.5].
Compound 16 was isolated as a colorless solid after evaporation of the
solvent. Yield: 51 mg, 98%. Anal. Calcd for C18H17NO3: C, 73.20; H,
5.80; N, 4.74. Found: C, 73.22; H, 5.93; N, 4.67. Mp: 98−100 °C. IR
(Nujol, cm−1): ν(CO), 1732, 1686. HRMS (ESI+, m/z): exact mass
calcd for C18H18NO3 [M + H]+ requires 296.1281, found 296.1288,
CDCl3): δ 173.0 (C3), 171.1 (C1), 140.3 (C5), 137.9 (C4), 135.5
(C5a), 134.9 (C9a), 131.3 (C7), 130.7 (C9), 128.1 (C8), 126.4 (C6),
33.0 (NMe), 26.5, 25.6 (CH2CH3), 14.0, 13.9 (CH2CH3).
Synthesis of 3-[Di(methoxycarbonyl)methyl]-2-methyl-3-
phenylisoindolin-1-one (15b). To a solution of 11b (137 mg,
0.21 mmol) in CHCl3 (15 mL) was added MeOH (17 μL, 0.42
mmol), and the mixture was stirred under a CO atmosphere (1.4 bar)
for 6 h, whereupon a black precipitate of Pd gradually formed. The
suspension was filtered through anhydrous MgSO4, the filtrate was
evaporated to dryness, and the residue was purified by column
chromatography on silica gel, using Et2O as the eluent (Rf = 0.50).
Compound 15b was isolated as a colorless solid after evaporation of
the solvent. Yield: 60 mg, 83%. Mp: 120−121 °C. Anal. Calcd for
C20H19NO5: C, 67.98; H, 5.42; N, 3.96. Found: C, 67.87; H, 5.34; N,
1
error = 2.35 ppm. H NMR (400.9 MHz, CDCl3): δ 7.87 (m, 1 H,
H7), 7.48 (td, 4JHH = 1.2 Hz, 3JHH = 7.2 Hz, 1 H, H5), 7.44 (td, 4JHH
=
4674
dx.doi.org/10.1021/om4006406 | Organometallics 2013, 32, 4664−4676

Organometallics
Article
1.2 Hz, 3JHH = 7.2 Hz, 1 H, H6), 7.37−7.28 (m, 3 H, Ph), 7.24 (m, 1
(C4a), 129.1 (C8), 127.6 (C7), 126.6 (C5), 123.8 (C8a), 104.7 (C4),
58.4 (COMe), 53.0 (CO2Me), 27.0 (NMe).
2
H, H4), 7.15−7.12 (m, 2 H, Ph), 3.57, 3.37 (AB system, JHH = 14.0
Hz, 2 H, CH2), 3.39 (s, 3 H, CO2Me), 2.91 (s, 3 H, NMe). 13C{1H}
APT NMR (100.8 MHz, CDCl3): δ 168.9 (CO2Me), 168.5 (C1),
148.7 (C3a), 138.9 (C, Ph), 131.8 (C5), 131.1 (C7a), 129.1 (CH, Ph),
128.5 (C6), 128.3, 125.8 (CH, Ph), 123.4 (C7), 122.3 (C4), 68.2
(C3), 51.9 (CO2Me), 39.1 (CH2), 25.0 (NMe).
ASSOCIATED CONTENT
■
S
* Supporting Information
Syntheses of 2-iodo-N-methylbenzamide and 2-iodo-N,N-
1
dimethylbenzamide. H NMR data of the mixture of 15a and
Synthesis of Dimethyl 2-((2-(Methylcarbamoyl)phenyl)-
(phenyl)methylene)malonate (17). A solution of 11b (154 mg,
0.23 mmol) in MeOH (15 mL) was stirred under a CO atmosphere
(1.4 bar) for 3 h, whereupon a black precipitate of Pd gradually
formed. The suspension was filtered through Celite, and the filtrate
was concentrated to dryness. The residue was chromatographed on
silica gel, using Et2O as the eluent [Rf = 0.35]. Compound 17 was
isolated as a colorless solid after evaporation of the solvent. Yield: 47
mg, 58%. Anal. Calcd for C20H19NO5: C, 67.98; H, 5.42; N, 3.96.
Found: C, 67.65; H, 5.57; N, 4.04. Mp: 152−154 °C. IR (Nujol,
cm−1): ν(NH), 3250; ν(CO), 1729, 1632. HRMS (ESI+, m/z): exact
mass calcd for C20H20NO5 [M + H]+ requires 354.1336, found
354.1340, error = 1.05 ppm. 1H NMR (400.9 MHz, CDCl3): δ 7.64−
7.61 (m, 1 H, Ar), 7.48−7.43 (m, 2 H, Ar), 7.35−7.25 (m, 4 H, Ar +
(tmedaH)TfO. Crystallographic data in CIF format for 2a, 3a,
7a, 11b, 14b, 15b, 18·CH2Cl2, and 19. Tables of crystallo-
graphic data. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jvs1@um.es (J.V.; http://www.um.es/gqo), p.jones@
tu-bs.de (P.G.J.).
■
Notes
The authors declare no competing financial interest.
3
Ph), 7.03−7.00 (m, 2 H, Ph), 6.81 (br q, JHH = 5.2 Hz, 1 H, NH),
ACKNOWLEDGMENTS
We thank Ministerio de Ministerio de Economıa y Com-
petitividad (Spain), FEDER (CTQ2011-24016), and Funda-
3.67 (s, 3 H, CO2Me), 3.65 (s, 3 H, CO2Me), 2.80 (d, 3JHH = 5.2 Hz, 1
H, NMe). 13C{1H} APT NMR (100.8 MHz, CDCl3): δ 168.8
(CONH), 167.0, 166.1 (CO2Me), 157.6 (CCCO2Me), 137.9 (C,
Ar), 137.8 (C, Ph), 136.1 (C, Ar), 130.2 (CH, Ph), 130.1, 129.5, 129.0
(CH, Ar), 128.6 (CH, Ph), 128.33 (CH, Ar), 128.29 (CH, Ph), 125.5
(CCCO2Me), 52.8, 52.5 (CO2Me), 26.7 (NHMe).
■
́
cion
grant to R.F.P.
́ ́
Seneca (04539/GERM/06) for financial support and a
Synthesis of [Pd(κ2C,O-C14H13O5)(tmeda)] (18). To a solution
of 10b (110 mg, 0.17 mmol) in MeOH (15 mL) was added NaOMe
(92 mg, 1.70 mmol), and the mixture was stirred for 15 h. The solvent
was removed under reduced pressure, and the remaining residue was
extracted with CH2Cl2 (6 × 5 mL). The combined extracts were
filtered through anhydrous MgSO4. Partial evaporation of the filtrate
(4 mL) and slow addition of n-hexane (30 mL) led to the formation of
an orange precipitate, which was filtered off, washed with n-hexane (3
× 3 mL), and vacuum-dried to give 18·CH2Cl2. Yield: 95 mg, 96%.
Anal. Calcd for C21H31Cl2N3O5Pd: C, 43.28; H, 5.36; N, 7.21. Found:
C, 42.88; H, 4.96; N, 7.10. Mp: 167−168 °C (dec). IR (Nujol, cm−1):
REFERENCES
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ν(CO), 1688, 1632. H NMR (400.9 MHz, CDCl3): δ 8.19 (m, 1 H,
H8), 7.33 (m, 1 H, H6), 7.25 (m, 1 H, H5), 6.98 (m, 1 H, H7), 5.30
(s, 2 H, CH2Cl2), 3.61 (s, 3 H, CO2Me), 3.51 (s, 3 H, COMe), 3.49 (s,
3 H, NMe), 3.05−2.98 (m, 1 H, CH2, tmeda), 2.80−2.74 (m, 1 H,
CH2, tmeda), 2.74 (s, 3 H, Me, tmeda), 2.72 (s, 3 H, Me, tmeda), 2.69
(s, 3 H, Me, tmeda), 2.66 (s, 3 H, Me, tmeda), 2.49−2.40 (m, 2 H,
CH2, tmeda). 13C{1H} APT NMR (75.5 MHz, CDCl3): δ 177.1
(CO2Me), 164.2 (CONMe), 137.5 (C4a), 131.7 (C6), 128.2 (C8),
119.71, 119.70 (C7, C5), 117.9 (C8a), 93.9 (C4), 79.4 (PdC), 64.5,
57.1 (CH2, tmeda), 54.1 (OMe), 51.8 (CO2Me), 50.7, 49.7, 48.1, 46.1
(Me, tmeda), 26.7 (NMe) (C3 not observed).
(5) Rousseaux, S.; Gorelsky, S. I.; Chung, B. K. W.; Fagnou, K. J. Am.
Chem. Soc. 2010, 132, 10692−10705.
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Synthesis of (E)-4-[Methoxy(methoxycarbonyl)methylene]-
2-methylisoquinoline-1,3(2H,4H)-dione (19). A solution of 18·
CH2Cl2 (127 mg, 0.22 mmol) in CHCl3 (15 mL) was stirred at 70 °C
for 2 d, whereupon a black precipitate of Pd gradually formed. The
solvent was evaporated to dryness, and the residue was extracted with
Et2O (8 × 5 mL). The combined extracts were filtered through
anhydrous MgSO4, and the resulting pale orange filtrate was
evaporated to dryness. The residue was purified by column
chromatography on silica gel, using Et2O as the eluent [Rf = 0.8].
Compound 19 was isolated as a colorless solid after evaporation of the
solvent. Yield: 25 mg, 42%. Anal. Calcd for C14H13NO5: C, 61.09; H,
4.76; N, 5.09. Found: C, 61.01; H, 4.42; N, 5.19. Mp: 116−119 °C
(dec). IR (Nujol, cm−1): ν(CO), 1734, 1696, 1657. HRMS (ESI+, m/
z): exact mass calcd for C14H14NO5 [M + H]+ requires 276.0866,
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dez, I.; Jones, P. G.; Vicente, J.
́
̃
́
̃
́
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1
found 276.0874, error = 2.90 ppm. H NMR (400.9 MHz, CDCl3): δ
G. Organometallics 2012, 31, 3361−3372.
8.36 (m, 1 H, H5), 8.31 (dd, 4JHH = 1.6 Hz, 3JHH = 7.6 Hz, 1 H, H8),
7.62 (ddd, 4JHH = 1.6 Hz, 3JHH = 7.2 Hz, 3JHH = 7.6 Hz, 1 H, H6), 7.43
(m, 1 H, H7), 4.09 (s, 3 H, COMe), 4.03 (s, 3 H, CO2Me), 3.39 (s, 3
H, NMe). 13C{1H} APT NMR (100.8 MHz, CDCl3): δ 165.4 (C3),
164.1 (C1), 163.1 (CO2Me), 161.7 (MeOCC), 133.4 (C6), 131.3
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