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Reactivity of Eight-Membered Palladacycles Arising from Monoinsertion of Alkynes into the Pd−C bond of Ortho-Palladated Phenethylamines toward Unsaturated Molecules. Synthesis of Dihydro-3-Benzazocinones, N7‑amino Acids, N7‑amino Esters, and 3‑Benzazepines ́ María-José Oliva-Madrid,† José-Antonio Garcıa-Ló pez,† Isabel Saura-Llamas,*,† Delia Bautista,‡ and José Vicente*,† †

Grupo de Quı ́mica Organometálica, Departamento de Quı ́mica Inorgánica, Universidad de Murcia, Apartado 4021, 30071 Murcia, Spain ‡ SAI, Universidad de Murcia. Apartado 4021, 30071 Murcia, Spain S Supporting Information *

ABSTRACT: From the reactions of isocyanides R3NC with some eight-membered palladacycles arising from the insertion of one molecule of alkyne into the Pd−C bond of the palladacycles derived from homoveratrylamine and phentermine it is possible to isolate three different types of mononuclear complexes containing (1) coordinated R3NC, (2) coordinated and inserted R3NC, or (3) an unprecedented η3-allyl ligand involving a ketenimine moiety. These complexes decompose under the appropriate conditions to afford metallic palladium and the corresponding eight-membered azacycles arising from C−N coupling processes. The eight-membered palladacycles react with CO in MeOH to yield Pd(0) and amino esters. A singular isomerization process from a fumarate to a maleate was observed and studied by DFT. When the reaction with CO is carried out in the presence of TlTfO, N7-amino acid derivatives can be obtained. This synthetic method can also be used to prepare the N5-amino acids derived from the ortho-metalated homoveratrylamine or phentermine. Finally, the treatment of one eight-membered palladacycle derived from phentermine with KtBuO in refluxing toluene, followed by addition of HTfO, afforded Pd(0) and a dihydro-3-benzazepinium salt. Crystal structures of every type of compound have been determined by Xray diffraction studies.

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INTRODUCTION Palladacycles react with internal alkynes to afford new metallacycles, resulting from the insertion of one, two, or three molecules into the Pd−C bond.1−10 Many studies on these insertion reactions have been mainly focused on the stoichiometric2,3,10−14 or catalytic15 synthesis of N-, O-, or Sheterocycles, upon decomposition of the enlarged palladacycles. As the reactivity of the latter toward other unsaturated ligands has been investigated only in a few cases,3,4,10,12,13,16−18 these sequential insertion reactions remain as an interesting research topic. Our research group has recently published the isolation of stable eight-membered C,N-palladacycles arising from insertion of one molecule of alkyne (Chart 1)19 into the Pd−C bond of ortho-palladated primary phenethylamines, and we were interested in studying the reactivity of these cyclopalladated complexes toward CO and RNC. In this paper we present the following reactivity of these eight-membered alkenyl palladacycles (1) Reactions with isocyanides give insertion products which upon depalladation afford eight-membered amidine © 2013 American Chemical Society

Chart 1

derivatives; in one case, an unprecedented η3-allyl complex of Pd(II) containing a ketenimine moiety is formed. (2) Reactions with carbon monoxide give N5- or N7-amino acids or their ester derivatives depending on the reaction conditions; an isomerization process, from a fumarate to a maleate derivative, promoted by hydrogen bond interactions, is observed. (3) Reactions with KtBuO, which, on heating, cause depalladation Received: August 1, 2013 Published: December 13, 2013 19

dx.doi.org/10.1021/om4010059 | Organometallics 2014, 33, 19−32

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to afford dihydro-3-benzazepines, through a C−N coupling process. The reactions with neutral N- and P-donor ligands gave some interesting results that have been published separately.20

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RESULTS AND DISCUSSION Reactions of Eight-Membered Palladacycles toward Isocyanides. Palladacycles A, D, and E reacted with tBuNC in a 1/2 molar ratio (Pd/tBuNC = 1/1) to give the mononuclear complexes 1a,d,e, respectively (Scheme 1), the crystal Scheme 1. Insertion Reactions of Isocyanides into the Pd−C Bond of Eight-Membered Palladacycles

Figure 1. Thermal ellipsoid plot (50% probability) of 1a along with the labeling scheme. The hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Pd(1)−Br(1) = 2.5437(2), Pd(1)−N(1) = 2.0973(15), Pd(1)−C(8) = 2.0243(17), Pd(1)−C(13) = 1.9283(18), C(7)−C(8) = 1.342(2), C(13)−N(2) = 1.153(2); Br(1)−Pd(1)−N(1) = 88.48(4), N(1)− Pd(1)−C(8) = 88.53(6), C(8)−Pd(1)−C(13) = 85.84(7), C(13)− Pd(1)−Br(1) = 97.23(5), Pd(1)−C(13)−N(2) = 174.96(15), C(13)−N(2)−C(14) = 169.97(17).

XyNC in a 1/2 molar ratio (Pd/XyNC = 1/1) afforded a mixture of the starting palladacycle A, the iminoacyl derivative 4a (Scheme 1), and another unidentified complex, likely the mononuclear derivative with the XyNC coordinated to the metallic center (analogous to 1a). The iminoacyl complex 4a could be prepared in excellent yield by using the appropriate palladacycle/XyNC molar ratio (1/4; Pd/XyNC = 1/2). The crystal structure of the iminoacyl complexes 3a·1/2Et2O and 4a· CHCl3·Et2O were determined by XRD (Supporting Information and Figure 2, respectively) and showed the palladium atoms coordinated to Br, the NH2 group, the terminal carbon atom of the isocyanide ligand, and the carbon atom of the inserted isocyanide (C9) in a slightly distorted square planar geometry. The nine-membered metallacycles adopted an approximately boat-chair conformation. For 3a·1/2Et2O, there were two independent molecules in the asymmetric unit. In 4a· CHCl3·Et2O, the mean planes of both Xy rings formed an angle of 52.2°, and the coordinated Xy ring was almost parallel to the nearest Ph substituent of the alkenyl fragment (angle of 6.7°), thus avoiding steric hindrance. The reaction of D with XyNC in a 1/2 molar ratio (Pd/ XyNC = 1/1) rendered a mixture of isomers 2d and 5d (Scheme 1), from which addition of Et2O afforded the crude complex 5d (approximately 33% yield). Subsequent addition of n-pentane gave crude 2d (approximately 35% yield). Their IR spectra were analogous, but crude 5d showed bands at 1812 (vs) and 2182 cm−1 (w), while crude 2d had the same two bands in the reverse order of intensities (1812 (w) and 2182 cm−1 (vs)). The higher energy band can be assigned to ν(CN) of the coordinated XyNC ligand in 2d and, correspondingly, that at 1812 cm−1 to the ketenimine moiety in 5d. The C, H, and N elemental analyses found for both solids, obtained from a variety of experiments, were ±0.4% of the calculated values for 2d·H2O or 5d·H2O. The 1H NMR spectra of both solids in CDCl3 show the presence of only a 2d/5d mixture (3/1 molar

structures of which were solved by XRD studies (see Figure 1 for that of 1a and the Supporting Information for the others). In all the complexes, the palladium atom forms part of an eightmembered ring that adopts an approximately twist-boat conformation. When the reaction of A and tBuNC was carried out in a 1/4 molar ratio (Pd/tBuNR3 = 1/2) at room temperature, the iminoacyl complex 3a was obtained, containing one inserted and one coordinated isocyanide (Scheme 1). Formation of the analogous iminoacyl complex was not observed when palladacycle D was used as the starting material. The reactivity of palladacycles A and D toward XyNC was different from that of tBuNC. Thus, the reaction of A and 20


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Figure 3. Thermal ellipsoid plot (50% probability) of complex 5d along with the labeling scheme. The hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Pd(1)−Cl(1) = 2.3692(4), Pd(1)−N(1) = 2.1581(12), Pd(1)−C(7) = 2.1806(13), Pd(1)−C(8) = 2.1376 (13), Pd(1)−C(9) = 2.0224(14), C(7)−C(8) = 1.4264(19), C(8)−C(9) = 1.4346(19), C(9)−N(2) = 1.2294(18); Cl(1)−Pd(1)−N(1) = 88.76(4), C(7)− C(8)−C(9) = 114.87(12), C(8)−C(9)−N(2) = 140.35(14), C(9)− N(2)−C(41) = 131.83(13).

Figure 2. Thermal ellipsoid plot (50% probability) of 4a·CHCl3·Et2O along with the labeling scheme. The solvent molecules and the hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Pd(1)−Br(1) = 2.5440(4), Pd(1)−N(1) = 2.097(2), Pd(1)−C(9) = 2.027(2), Pd(1)−C(41) = 1.943(3), C(7)−C(8) = 1.344(3), C(8)−C(9) = 1.496(3), C(9)−N(3) = 1.255(3), C(41)−N(2) = 1.153(3); Br(1)− Pd(1)−N(1) = 89.20(6), N(1)−Pd(1)−C(9) = 88.50(9), C(9)− Pd(1)−C(41) = 93.22(9), C(41)−Pd(1)−Br(1) = 88.94(7), C(8)− C(9)−N(3) = 119.3(2), C(9)−N(3)−C(51) = 125.2(2), Pd(1)− C(9)−N(3) = 128.32(18), Pd(1)−C(41)−N(2) = 172.7(2), C(41)− N(2)−C(42) = 170.6(3).

Scheme 2. Formation of η3-Allyl Complex 5d

ratio), proving that they are in a slow equilibrium on the NMR time scale. At 50 °C, the 1H NMR of the mixture did not change significantly, although the ratio among complexes slightly increased (2d/5d = 4/1). Both complexes showed only one resonance corresponding to the two methyls of the Xy group. The nature of complex 5d could only be known after obtaining single crystals suitable for XRD studies by slow diffusion of Et2O into a solution of the equilibrium mixture in CH2Cl2, and its structure was unequivocally determined (Figure 3). Surprisingly, it showed a η3-allyl monomeric structure with the palladium atom in a square planar geometry (mean deviation from the plane X−Pd(1)−Cl(1)−N(1) 0.013 Å, where X is the centroid of the C(7), C(8), and C(9) atoms) and the chloro ligand and the amino group of the metalated fragment were coordinated in cis positions. The other two coordination sites were occupied by the propenyl-imine ligand, which was bonded via C(7), C(8), and C(9), with a C(7)− C(8)−C(9) angle of 114.87(12)°. The distance C(9)−N(2) (1.2294 Å) was shorter than those found for CN bonds in iminoacyl complexes containing inserted XyNC (from 1.258(3) to 1.278(2) Å),7,14,21−23 whereas the angle C(8)−C(9)−N(2) (140.35°) was greater than that expected for a sp2 carbon. These two features suggested a significant contribution of the resonance form IIb (Scheme 2; see below). Two adjacent molecules of complex 5d were connected through two hydrogen bonds (involving one H of the NH2 groups and the chlorine atoms), giving dimers (see the Supporting Information). Pfeffer et al.24 proposed the formation of a polymeric Pd(II) complex containing an η3-bonded N−C−N unit from the deprotonation reaction of a C,N-amidine palladacycle, although it could not be fully characterized because of its insolubility.

We could explain the formation of 5d by assuming that 2d underwent the insertion of the coordinated isocyanide, giving the iminoacyl-intermediate I (Scheme 2). Then, displacement of the chloro bridging ligand by the double bond of the alkenyl moiety afforded the η3-allyl complex. The contribution of the resonance form IIb to the bonding in complex 5d explained the frequency observed for the ν(CN) in its IR spectrum, as νasym(CN) of free ketenimine usually appears as a very strong band at 2050−2000 cm−1.25 21


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The accepted mechanism of the insertion of isocyanides into the Pd−C bond involves (1) coordination of the ligand to the metal center and (2) migratory insertion of the aryl group to the coordinated isocyanide.26−31 The migration rate of the aryl group increases when the electrophilicity of the isocyanide and the nucleophilicity of the carbon atom bonded to palladium(II) are increased.23,30,32 This mechanism could easily explain (1) why XyNC inserts more quickly than tBuCN and (2) the different reactivities of palladacycles A and D, which could be attributed to the stronger nucleophilicity of the carbon atom bonded to palladium(II) in the functionalized homoveratrylamine derivative.33 The easy insertion of the isocyanide into the Pd−C bond of A resembles the behavior of the six-membered palladacycle derived from homoveratrylamine33 or benzyl methyl sulfide,27,28 which underwent rapid isocyanide insertion at room temperature, and is in contrast with that exhibited by complexes derived from classical N,N-dimethylbenzylamines, for which high temperatures or an excess of isocyanide was required to obtain the iminoacyl complexes.26,31 The formation of complex 5d is more difficult to explain, as there is no precedent for such a complex, in which, in order to complete the four-coordination, Pd(II) preferred to bond an olefinic moiety (and to generate a η3-allyl complex) instead of forming a chloro-5,26,28,31 or an iminoacyl-bridged dinuclear complex.22,27−29,34 Rourke et al. have described a singular cyclopalladated complex in which the metal was coordinated to the C,N-ligand and a chloro ligand and had a Pd···H2C agostic interaction.35 When the iminoacyl complex 4a was treated with TlTfO (TlCF3SO3) and heated in toluene, the amidinium salt 6a was obtained (69% yield; Scheme 1), along with metallic palladium. The amidinium salt 6d was prepared from the mixture of complexes 2d + 5d, by reacting it with TlTfO and then heating at 110 °C in toluene. The salt 6d was difficult to purify, and thus it was converted to the corresponding free amidine 7d by treatment with Na2CO3 (Scheme 3). We had previously used

Figure 4. Thermal ellipsoid plot (50% probability) of the cation of compound 6a·Et2O along with the labeling scheme. The solvent molecule and the hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): N(1)−C(2) = 1.4602(17), C(1)−C(2) = 1.5448(19), C(1)−C(10A) = 1.5183(19), C(6A)−C(10A) = 1.3970(18), C(6A)−C(6) = 1.4944(17), C(5)−C(6) = 1.3449(18), C(4)−C(5) = 1.4970(17), N(1)−C(4) = 1.3143(17), N(2)−C(4) = 1.3190(17); N(1)−C(2)− C(1) = 113.60(11), C(2)−C(1)−C(10A) = 117.87(11), C(1)− C(10A)−C(6A) = 124.32(12), C(10A)−C(6A)−C(6) = 122.32(12), C(6A)−C(6)−C(5) = 119.66(11), C(6)−C(5)−C(4) = 118.93(11), C(5)−C(4)−N(1) = 118.69(11), C(4)−N(1)−C(2) = 121.67(11), C(4)−N(2)−C(41) = 123.05(11), N(1)−C(4)−N(2) = 122.21(12).

compound 6a, the cationic units are connected between them and to the triflate groups through hydrogen bonds, giving layers parallel to the ab plane (see the Supporting Information). Insertion of CO into the Pd−C Bond of EightMembered Palladacycles. Synthesis of N7-amino Esters and N7-amino Acids. It is well-known that carbon monoxide readily inserts into the Pd−C bond of alkyl and aryl complexes to afford organometallic acyl 38 and aroyl derivatives,4,8,13,14,27,28,39 or organic compounds upon further decomposition.10,17,40−43 It is also well-known that the nature of these organic derivatives greatly depends on the reaction conditions, particularly the solvent. Thus, when C,N-palladacycles are used as starting materials, N-heterocycles6,17−19,23,36,43,44 or functionalized derivatives of the starting compounds containing an ester group in the ortho position9,19,45,46 are obtained. We have previously reported that the reactions of palladacycles A−F with CO in CHCl3 led to the synthesis of the corresponding dihydro-3-benzazocinones.18 When complexes A−F reacted with CO in MeOH, decomposition to metallic palladium took place and the esters 8a−f were isolated from the reaction mixture in moderate to excellent yields (47−92%; Scheme 4).9,19,42,46 Palladium-catalyzed carbobutoxylation of vinylic halides has been reported,41 and very recently, Williams et al.47 have described the Pd-catalyzed methoxycarbonylation of phenylacetylene using aluminum triflate and other acid-type promoters. It is important to note that the insertion of CO into the Pd−C bond of these organometallic complexes is stereospecific and occurred with retention of the configuration of the double bond of the alkenyl fragment: that is, the relative

Scheme 3. Synthesis of the 2,3-Dihydro-3-benzazocine Derivative 7d

both synthetic routes to prepare 2-aminoisoindolinium, 3,4dihydroisoquinolinium, and hexahydro-3-benzo[d]azocinium salts derived from five-,31 six-,23,36 or eight-membered C,N palladacycles.37 The NMR spectra of compounds 6a and 7d are in agreement with the proposed structures. Additionally, the crystal structure of 6a·Et2O has been determined by an XRD study (Figure 4). The eight-membered aza ring adopts a boat conformation, and the atoms C(2), N(1), C(4), N(2), C(41), and C(5) are almost coplanar (mean deviation from the plane 0.0313 Å). Delocalization of electron density among the atoms N(1), C(4), and N(2) is confirmed by the similar N(1)−C(4) and N(2)−C(4) bond distances (1.3143(17) and 1.3190(17) Å) and the angles around both nitrogen atoms (C(2)−N(1)− C(4), 121.67(11)°; C(4)−N(2)−C(41), 123.05(11)°). In 22


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The structures of several conformations for the fumarate (compound 8e, structures T; Chart 2) and maleate derivatives

Scheme 4. Synthesis of Esters Derived of Eight-Membered Palladacycles

Chart 2. Optimized Structures of Several Conformations for the Fumarate and Maleate Derivatives 8e,e′

positions of the substituents at the double bond did not change upon carbonylation. Surprisingly, in CHCl3 solution, the fumarate derivative 8e (E isomer) underwent an isomerization process to render a mixture of 8e and the maleate derivative 8e′ (Z isomer), where both CO2Me groups were in cis positions (final ratio 8e/8e′ = 1/5, after 48 h at room temperature or 12 h at 60 °C; Scheme 5). The same mixture (8e/8e′ = 1/5) was directly obtained Scheme 5. Proposed Mechanism for Isomerization of 8e

(compound 8e′, structures C; Chart 2) were optimized through DFT calculations at the B3LYP/6-31G* level, taking into account different possibilities for intramolecular hydrogen bonds between the NH3 and CO2Me groups. Thus, the ammonium group could interact with one (T1, T2; Chart 2) or two oxygen atoms of the ester groups of the alkenyl fragment (C1−C3, T3; Chart 2). Comparing the relative energies of the optimized structures, we could observe that (1) the structures with two intramolecular hydrogen bonds were more stable than those containing only one interaction and (2) the most stable structures (C1 and C2) correspond to the maleate derivate. The difference in energy between the maleate structure C1 and the most stable configuration for the fumarate derivative, T3, is 2.0 kcal/mol. The higher stability of the maleate isomers (C1 and C2) with respect to the fumarate isomers (T) could explain the E to Z isomerization process observed experimentally. In order to discard the possible steric influence of the substituents in the stability of the E and Z configurations, we carried out the optimization of the analogue maleate and fumarate esters, replacing the NH3 group for a methyl group: that is, a moiety with similar steric requirements that is much less prone to form hydrogen bonds. In this case the fumarate derivative is slightly more stable than the maleate species (ΔE = 0.26 kcal/mol). Thus, we can consider that this unusual isomerization from fumarate to maleate derivatives is promoted by intramolecular hydrogen bond interactions. When the reactions with CO were performed using the cationic palladacycles derivatives of D−F, generated in situ by the addition of TlTfO in acetone, decomposition to metallic palladium took place and the corresponding ammonium salts of amino acids 9 were isolated (Scheme 6). A possible reaction pathway would involve the formation of an intermediate acyl

when the palladacycle E was stirred with CO in MeOH for 48 h. Both isomers were distinguished by a NOESY experiment carried out on the mixture 8e + 8e′, which showed the correlation between the methoxy groups of the Z isomer (8e′). No correlation was observed for the methoxy groups of the E isomer 8e. This E to Z isomerization process (fumarate to maleate) is the opposite of the well-known alkyl maleate to fumarate isomerization, which occurs in the presence of nucleophiles such as primary or secondary amines.48 A logical reaction pathway for the isomerization (Scheme 5) would involve (1) proton transfer from the ammonium group to one of the carbonyl moieties, rendering a carbocation that could be stabilized by the phenyl group, (2) rotation of the σ C−C bond, and (3) regeneration of the ammonium group and restoration of the double CC bond with a Z configuration. 23


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Scheme 6. Synthesis of Amino Acids Derived from Eightand Six-Membered Palladacycles

Figure 5. Thermal ellipsoid plot (50% probability) of the cation of compound 8a along with the labeling scheme. The hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): N(1)−C(11) = 1.488(3), C(11)−C(12) = 1.533(2), C(2)−C(12) = 1.518(2), C(1)−C(2) = 1.397(2), C(1)− C(7) = 1.492(2), C(7)−C(8) = 1.350(2), C(8)−C(9) = 1.506(2), C(9)−O(3) = 1.205(2), C(9)−O(4) = 1.332(2); N(1)−C(11)− C(12) = 111.29(14), C(2)−C(12)−C(11) = 113.32(14), C(1)− C(2)−C(12) = 123.14(15), C(2)−C(1)−C(7) = 122.09(15), C(1)− C(7)−C(8) = 121.60(15), C(7)−C(8)−C(9) = 119.10(15), O(3)− C(9)−C(8) = 125.40(16), O(4)−C(9)−C(8) = 110.92(15), O(3)− C(9)−O(4) = 123.68(16).

complex (common to the formation of esters 8), followed by the nucleophilic attack of H2O (present in the reaction mixture) on the carbonyl group. This method to obtain the ammonium triflates of the amino acids was successfully applied to the starting six-membered palladacycles. In this case, the reaction of complexes G and H yielded the corresponding ammonium salts 10g,h, which contained hydroxocarbonyl substituents in the aromatic rings (Scheme 6). Yu et al. have reported the Pd(II)-catalyzed regioselective carboxylation of aryl and vinyl carboxylic acids under 1 atm of CO to give dicarboxylic derivatives.49 This carboxylation protocol has also been applied successfully to the synthesis of N-anthranilic acids from anilides.50 All of the organic derivatives obtained by reaction of eightmembered palladacycles and CO were characterized by IR and NMR spectroscopy and exact mass. Additionally, the crystal structures of compounds 8a,d, 9d·Me2CO, and 9f have been determined by XRD studies (Figures 5 (8a) and 6 (9d· Me2CO), and the Supporting Information). All of these compounds show an intramolecular hydrogen bond between the oxygen atom of the carbonyl group and one of the hydrogen atoms of the NH3 group. In addition, the organic units were associated through hydrogen bonds (some of them involving the halide anion) to give double chains along the (110) direction (8a) or layers parallel to the ab plane (8d, 9d· Me2CO, 9f). The 1H NMR spectra of amino esters 8 and amino acids 9 show the inequivalence of the CH2 protons and the CMe2 methyl groups, which could arise from the presence of strong intramolecular hydrogen bonds in solution between the NH3 and carbonyl groups. The ammonium salts derived from amino esters (8) and amino acids (9 and 10) showed an intense absorption band in the infrared spectra corresponding to

Figure 6. Thermal ellipsoid plot (50% probability) of the cation of compound 9d·Me2CO along with the labeling scheme. The solvent molecule and the hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): N(1)−C(10) = 1.517(2), C(10)−C(11) = 1.545(2), C(2)−C(11) = 1.515(2), C(1)−C(2) = 1.404(2), C(1)−C(7) = 1.502(2), C(7)− C(8) = 1.345(2), C(8)−C(9) = 1.500(2), O(1)−C(9) = 1.2178(19), O(2)−C(9) = 1.3232(19); N(1)−C(10)−C(11) = 109.23(12), C(2)−C(11)−C(10) = 118.02(13), C(1)−C(2)−C(11) = 122.55(13), C(2)−C(1)−C(7) = 122.77(13), C(1)−C(7)−C(8) = 122.27(13), C(7)−C(8)−C(9) = 118.30(13), O(1)−C(9)−C(8) = 124.39(14), O(2)−C(9)−C(8) = 112.40(13), O(1)−C(9)−O(2) = 123.21(14).

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ν(CO) of the carboxylic substituents (1705−1728 cm−1 for CO2Me and 1622−1698 cm−1 for CO2H). The ammonium salts 8b,c,e,f showed lower molar conductivities in acetone (9− 22 Ω−1 mol−1 cm2)51 than those expected for 1/1 electrolytes, which could be attributed to the existence of strong hydrogen bonds in solution between the chloride or bromide anion and the hydrogen atoms of the NH3 group of the organic cation. Synthesis of 3-Benzazepines through C−N Coupling. The treatment of palladacycle D with KtBuO in refluxing toluene, followed by addition of HTfO, afforded Pd(0) and the 3-benzazepinium salt 11d, arising from a C−N coupling process (Scheme 7). A very similar reaction was reported by

The 3-benzazepine nucleus is part of the skeleton of numerous compounds with great potential as antileukemic,52 antihypertensive,53 and antipsychotic54 drugs and in the treatment of Alzheimer’s disease,55 obesity,56 and tobacco addiction syndrome.57

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CONCLUSION The eight-membered palladacycles undergo RNC and CO insertion into the Pd−C bond to render Pd(0) and (1) dihydro-3-benzazocine derivatives and (2) the N7-amino acids or N7-amino esters derivatives (depending on the experimental conditions). One of those N7-amino esters is a dimethyl diarylfumarate, which undergoes a singular isomerization process to give the corresponding maleate. On the basis of DFT calculations, we propose that the special stability of this maleate arises from the presence of intramolecular hydrogen bonds. The method used to obtain the amino acids can be applied to the synthesis of carboxylic acids derived from phentermine and homoveratrylamine. Finally, the eightmembered palladacycle containing phentermine undergoes a C−N coupling reaction to render a 3-benzazepium salt.

Scheme 7. Synthesis of 3-Benzazepinium Salt 11da

a

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Legend: (i) KtBuO + Δ − KCl − tBuOH − Pd(0); (ii) HTfO,

Nieto el al. using as the starting palladacycle the complex arising from monoinsertion of diphenylacetylene into the Pd− C bond of ortho-metalated methyl phenylglycinate, but they found unclear results when depalladation reactions were attempted.6 The crystal structure of the dihydro-3-benzazepinium triflate 11d shows that the azepane ring adopts a twist-boat conformation (Figure 7). The organic cations are associated with the triflate groups through hydrogen bonds to form dimers (see the Supporting Information).

EXPERIMENTAL SECTION

Caution! Special precautions should be taken in handling thallium(I) compounds because of their toxicity. General Procedures. Infrared spectra were recorded on a PerkinElmer 16F-PC-FT spectrometer. C, H, and N analyses, conductance measurements, and melting point determinations were carried out as described elsewhere.33 Unless otherwise stated, NMR spectra were recorded in CDCl3 on Bruker Avance 300, 400, and 600 spectrometers. Chemical shifts are referenced to TMS. Signals in the 1 H and 13C NMR spectra of all complexes were assigned with the help of APT, HMQC, and HMBC techniques. Copies of 1H and 13C-APT NMR spectra of compounds 6−11 are included in the Supporting Information. High-resolution ESI mass spectra were recorded on an Agilent 6220 Accurate Mass TOF LC/MS spectrometer. Reactions were carried out at room temperature without special precautions against moisture unless specified otherwise. Chart 3 gives the numbering schemes for the new palladacycles and the organic derivatives. The palladacycles [Pd{C,N-C(Ph)C(R)C6H2CH2CH2NH2-2, (OMe)2-4,5}(μ-Br)]2 (R = Ph (A), CO2Me (B), Me (C)), [Pd{C,N-C(Ph)C(R)C6H4CH2CMe2NH2-2}(μ-Cl)]2 (R = Ph

Chart 3. Numbering Scheme for Eight- and Nine-Membered Palladacycles and the Organic Derivatives

Figure 7. Thermal ellipsoid plot (50% probability) of the cation of compound 11d along with the labeling scheme. The hydrogen atoms bonded to carbon have been omitted for clarity. Selected bond lengths (Å) and angles (deg): N(1)−C(9) = 1.5422(17), C(9)−C(10) = 1.5330(19), C(2)−C(10) = 1.5078(19), C(1)−C(2) = 1.4054(19), C(1)−C(7) = 1.4879(19), C(7)−C(8) = 1.3496(19), N(1)−C(8) = 1.4809(17); N(1)−C(9)−C(10) = 107.63(10), C(2)−C(10)−C(9) = 114.02(11), C(1)−C(2)−C(10) = 119.97(12), C(2)−C(1)−C(7) = 120.57(12), C(1)−C(7)−C(8) = 121.94(12), C(7)−C(8)−N(1) = 116.58(12), C(8)−N(1)−C(9) = 116.97(10). 25


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(400.91 MHz): δ 1.42 (s, 3 H, Me, CMe2), 1.43 (s, 3 H, Me, CMe2), 1.50 (s, 9 H, CMe3), 1.82 (br d, 1 H, NH2, 2JHH = 10.8 Hz), 2.70 (d, 1 H, CH2Ar, 2JHH = 14.0 Hz), 2.95 (br d, 1 H, NH2, 2JHH = 10.4 Hz), 3.02 (d, 1 H, CH2Ar, 2JHH = 14.4 Hz), 3.43 (s, OMe), 7.16−7.20 (m, 3 H, o-H from Ph + H3), 7.22−7.34 (m, 6 H, Ph + Ar). 13C{1H} NMR (100.81 MHz): δ 27.5 (s, Me, CMe2), 30.0 (s, CMe3), 35.8 (s, Me, CMe2), 44.4 (s, CH2Ar), 51.3 (s, OMe), 57.0 (s, CMe2), 57.9 (s, CMe3), 125.8 (s, o-CH, Ph), 126.5 (s, CH, C6), 126.6 (s, p-CH, Ph), 127.0 (s, CH, C5), 127.2 (t, partially obscured by the resonance of C5, CN, 2JCN = 18.9 Hz), 128.4 (s, CH, C3), 128.5 (s, m-CH, Ph), 132.4 (s, C(CO2Me)), 132.5 (s, CH, C4), 136.7 (s, C1), 142.4 (s, C2), 144.8 (s, i-C, Ph), 164.3 (s, CO), 169.9 (s, C−Pd). Single crystals of 1e·1/5H2O suitable for an X-ray diffraction study were obtained by slow diffusion of n-pentane into a solution of 1e in CHCl3. Synthesis of [Pd{C,N-C(Ph)C(Ph)C6H4CH2CMe2NH2-2}Cl(CNXy)]·H2O (2d·H2O) and the η3-Allyl Complex 5d·H2O. XyNC (35 mg, 0.267 mmol) was added to a solution of complex D (125 mg, 0.133 mmol) in CH2Cl2 (15 mL), and the resulting solution was stirred for 15 min at 0 °C. The mixture was filtered through a plug of Celite, the filtrate was concentrated to ca. 1 mL, Et2O (20 mL) was added, and the mixture was stirred for 10 min. The suspension was filtered, and the bright yellow solid was washed with Et2O (2 × 3 mL) and air-dried to afford a mixture highly enriched in complex 5d·H2O (yield 54 mg, 0.087 mmol, 33%; IR (cm−1) ν(CN) 1812 vs). The filtrate was concentrated to ca. 1 mL, and n-pentane (20 mL) was added. The suspension was filtered, and the yellow solid was washed with n-pentane (2 × 3 mL) and air-dried to afford a mixture highly enriched in complex 2d·H2O (yield 57 mg, 0.092 mmol, 35%; IR (cm−1) ν(CN) 1182 s). Elemental analyses of both mixtures were obtained. Anal. Calcd for C33H33ClN2Pd·H2O (617.509): C, 64.19; H, 5.71; N, 4.54. Found for the solid enriched in 5d·H2O: C, 64.40; H, 5.69; N, 4.59. Found for the solid enriched in 2d·H2O: C, 64.36; H, 5.84; N, 4.62. The 1H NMR spectra of both solids corresponded to a mixture of (2d + 5d)·H2O (ratio ca. 3/1). 1H NMR (300.1 MHz): 2d, δ 1.44 (s, 3 H, Me, CMe2), 1.54 (s, 3 H, Me, CMe2), 1.81 (br d, 1 H, NH2, 2JHH = 10.5 Hz), 2.45 (s, 6 H, Me, Xy), 2.82 (d, 1 H, CH2, 2JHH = 14.1 Hz), 2.97 (br d, 1 H, NH2, 2JHH = 10.2 Hz), 3.17 (d, 1 H, CH2, 2 JHH = 14.1 Hz), 6.78−6.82 (m, aromatics), 6.93−7.07 (m, aromatics), 7.10−7.25 (m, aromatics), 7.28−7.38 (m, aromatics); 5d (selected data), δ 1.09 (s, 3 H, Me, CMe2), 1.22 (s, 3 H, Me, CMe2), 1.88 (s, 6 H, Me, Xy). The signals corresponding to the aromatic protons of both complexes were overlapped. The 1H NMR of the mixture showed a singlet at 1.59 ppm (2 H), which was assigned to the crystallization water. Single crystals of 5d suitable for an X-ray diffraction study were obtained by slow diffusion of Et2O into a solution of (2d + 5d)·H2O in CH2Cl2. Synthesis of [Pd{C,N-C(NtBu)C(Ph)C(Ph)C6H2CH2CH2NH2-2,(OMe)2-4,5}Br(CNtBu)]·H2O (3a·H2O). tBuNC (0.062 mL, 0.551 mmol) was added to a suspension of complex A (150 mg, 0.138 mmol) in CH2Cl2 (20 mL), and the resulting solution was stirred for 30 min. The mixture was filtered through a plug of Celite, the filtrate was concentrated to ca. 1 mL, and n-pentane (30 mL) was added. The suspension was filtered, and the solid was washed with n-pentane (2 × 5 mL) and air-dried to afford crude complex 3a· H2O as a yellow solid. Yield: 124 mg, 0.170 mmol, 62%. An analytically pure sample of complex 3a·H2O was obtained by recrystallization from CH2Cl2/n-pentane, drying the sample in a vacuum oven at 60 °C for 16 h. Mp: 179 °C. Anal. Calcd for C34H42BrN3O2Pd·H2O (729.066): C, 56.01; H, 6.08; N, 5.76. Found: C, 55.94; H, 5.95; N, 5.95. IR (cm−1): ν(NH) 3504 br m, 3314 m, 3256 w, 3200 w; ν(CN) 2199 s. 1H NMR (400.91 MHz): δ 1.12 (s, 9 H, Me, tBu-coordinated), 1.33 (s, 9 H, Me, tBu-inserted), 1.53 (s, 2 H, H2O), 1.66−1.74 (m, 1 H, NH2), 2.75 (br d, 1 H, NH2, 2JHH = 9.9 Hz), 3.01 (br d, 1 H, CH2Ar, 2JHH = 11.2 Hz), 3.16 (m, 1 H, CH2N), 3.76−3.86 (m, partially obscured by the MeO signal, 1 H, CH2N), 3.76 (s, 3 H, MeO), 3.86−3.89 (m, partially obscured by the MeO signal, 1 H, CH2Ar), 3.88 (s, 3 H, MeO), 6.65 (s, 1 H, H6), 6.71 (s, 1 H, H3), 6.81−6.85 (m, 2 H, o-H, Ph), 6.98−7.00 (m, 3 H, 2 H of m-H + 1 H of p-H, Ph), 7.18−7.20 (m, 3 H, 2 H of m-H + 1 H of p-H, Ph), 7.31−7.33 (m, 2 H, o-H, Ph). 13C{1H} NMR (100.81 MHz): δ 29.7 (s,

(D), CO2Me (E), Me (F)), [Pd{C,N-C6H2CH2CH2NH2-2,(OMe)24,5}2(μ-Br)2] (G), and [Pd(C,N-C6H4CH2CMe2NH2-2)2(μ-Cl)2] (H) were prepared as previously reported.18,33,58 tBuNC, XyNC, HTfO (HOSO2CF3) (Fluka), CO (gas, Air Products), and Na2CO3 (Baker) were used as received. TlTfO was prepared by reaction of Tl2CO3 and HOSO2CF3 (1/2) in water and recrystallized from acetone/Et2O. Synthesis of [Pd{C,N-C(Ph)C(Ph)C6H2CH2CH2NH2-2,(OMe)24,5}Br(CNtBu)] (1a). tBuNC (0.021 mL, 0.184 mmol) was added to a suspension of palladacycle A (100 mg, 0.092 mmol) in CH2Cl2 (20 mL), and the resulting solution was stirred for 4 h. The mixture was filtered through a plug of Celite, the filtrate was concentrated to ca. 1 mL, and Et2O (30 mL) was added. The suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and air-dried to afford crude complex 1a as a pale yellow solid. Yield: 98 mg, 0.156 mmol, 84%. An analytically pure sample of complex 1a was obtained by recrystallization from CH2Cl2/Et2O, drying the sample in a vacuum oven at 60 °C for 16 h. Mp: 192 °C. Anal. Calcd for C29H33BrN2O2Pd (627.917): C, 55.47; H, 5.30; N, 4.46. Found: C, 55.15; H, 5.45; N, 4.47. IR (cm−1): ν(NH) 3437 br w, 3301 m, 3214 m, 3133 w; ν(CN) 2195 s. 1H NMR (300.1 MHz): δ 1.54 (s, 9 H, Me, tBu), 1.58−1.65 (m, partially obscured by the tBu signal, 1 H, NH2), 2.80 (m, 1 H, CH2Ar), 2.95 (dd, 1 H, CH2Ar, 2JHH = 14.1, 3JHH = 4.5 Hz), 3.07 (br d, 1 H, NH2, 2JHH = 10.2 Hz), 3.23 (m, 1 H, CH2N), 3.31−3.44 (m, 1 H, CH2N), 3.75 (s, 3 H, MeO), 3.96 (s, 3 H, MeO), 6.43 (s, 1 H, H6), 6.84−6.87 (m, 3 H, H3 + 2 H of o-H Ph), 6.98−7.04 (m, 3 H, 2 H of m-H + 1 H of p-H, Ph), 7.05−7.19 (m, 6 H, 2 H of m-H + 2 H of o-H + 1 H of p-H, Ph). 13C{1H} NMR (100.81 MHz): δ 30.3 (s, Me, tBu), 33.7 (s, CH2Ar), 47.3 (s, CH2N), 55.8 (s, MeO), 56.0 (s, MeO), 111.2 (s, CH, C3), 112.0 (s, CH, C6), 125.5 (s, p-CH, Ph), 125.7 (s, p-CH, Ph), 127.6 (s, m-CH, Ph), 128.7 (s, m-CH + o-CH, Ph), 129.4 (s, oCH, Ph), 132.6 (s, C1), 139.0 (s, C2), 139.2 (s, C-Ar), 140.3 (s, i-C, Ph), 144.7 (s, i-C, Ph), 147.9 (s, C4), 148.5 (s, C5), 150.1 (s, C−Pd). The 13C resonances corresponding to CN and CMe3 were not observed. Single crystals suitable for an X-ray diffraction study were obtained by slow diffusion of Et2O into a solution of 1a in CHCl3. Synthesis of [Pd{C,N-C(Ph)C(Ph)C6H4CH2CMe2NH2-2}Cl(CNtBu)] (1d). tBuNC (0.025 mL, 0.220 mmol) was added to a suspension of palladacycle D (100 mg, 0.107 mmol) in CH2Cl2 (10 mL), and the resulting solution was stirred for 15 min. The mixture was filtered through a plug of MgSO4, the solvent was removed from the filtrate, and Et2O (7 mL) was added. The suspension was filtered, and the solid was air-dried to afford complex 1d as a yellow solid. Yield: 70 mg, 0.127 mmol, 59%. Dec pt: 175 °C. Anal. Calcd for C29H33ClN2Pd (551.45): C, 63.16; H, 6.03; N, 5.08. Found: C, 63.09; H, 7.76; N, 5.07. IR (cm−1): ν(NH) 3298 m, 3191 m, 3119 m; ν(CN) 2200 s. 1H NMR (300.1 MHz): δ 1.41 (s, 3 H, Me, CMe2), 1.49 (s, 3 H, Me, CMe2), 1.53 (s, 9 H, Me, tBu), 1.72 (br d, 1 H, NH2, 2JHH = 11.4 Hz), 2.78 (d, 1 H, CH2, 2JHH = 13.8 Hz), 2.88 (br d, 1 H, NH2, 2 JHH = 10.2 Hz), 3.12 (d, 1 H, CH2, 2JHH = 14.1 Hz), 6.77−6.80 (m, 2 H, Ph), 6.95−7.36 (m, 12 H, Ar + Ph). 13C{1H} NMR (75.45 MHz): δ 27.5 (s, Me, CMe2), 30.2 (s, Me, tBu), 35.9 (s, Me, CMe2), 44.6 (s, CH2), 56.9 (s, CMe2), 125.6 (s, CH), 125.7 (s, CH), 126.4 (s, CH), 126.9 (s, CH), 127.6 (s, CH), 128.6 (s, CH), 128.8 (s, CH), 128.9 (s, CH), 129.4 (s, CH), 132.2 (s, CH), 136.9 (s, C), 139.7 (s, C), 140.5 (s, C), 144.6 (s, C), 147.6 (s, C), 148.8 (s, C). The 13C resonances corresponding to CN and CMe3 were not observed. Single crystals of 1d·1/2CHCl3 suitable for an X-ray diffraction study were obtained by slow diffusion of n-pentane into a solution of 1d in CHCl3. Synthesis of [Pd{C,N-C(Ph)C(CO2Me)C6H4CH2CMe2NH2-2}Cl(CNtBu)] (1e). tBuNC (0.05 mL, 0.443 mmol) was added to a solution of palladacycle E (180 mg, 0.201 mmol) in CH2Cl2 (15 mL), and the resulting yellow solution was stirred for 20 min. The mixture was concentrated to ca. 2 mL, and n-pentane (30 mL) was added. The resulting suspension was filtered, and the solid was washed with npentane (2 × 5 mL) and air-dried to afford crude complex 1e as a pale yellow solid. Yield: 185 mg, 0.347 mmol, 86%. The solid was recrystallized from CH2Cl2/Et2O (recrystallization yield: 53%). Dec pt: 194 °C. Anal. Calcd for C25H31ClN2O2Pd (333.406): C, 56.29; H, 5.86; N, 5.25. Found: C, 55.93; H, 6.31; N, 5.25. IR (cm−1): ν(NH) 3190 m, 3122 m; ν(CN) 2207 vs; ν(CO) 1713 vs. 1H NMR 26


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Article

Me, tBu-coordinated), 30.7 (s, CH2Ar), 31.1 (s, Me, tBu-inserted), 44.5 (s, CH2N), 55.9 (s, MeO), 55.9 (s, MeO), 108.1 (s, CH, C6), 114.2 (s, CH, C3), 125.2 (s, C1), 126.1 (s, p-CH, Ph), 126.9 (s, p-CH, Ph), 127.4 (s, m-CH, Ph), 127.8 (s, m-CH, Ph), 128.8 (br s, CN, tBucoordinated), 129.8 (s, o-CH, Ph), 131.1 (s, o-CH, Ph), 131.4 (s, CAr), 136.3 (s, C2), 138.2 (s, i-C, Ph), 141.0 (s, i-C, Ph), 145.0 (s, C− Pd), 147.5 (s, C4), 148.4 (s, C5), 171.9 (s, CN, tBu-inserted). Single crystals of 3a·1/2Et2O suitable for an X-ray diffraction study were obtained by slow diffusion of Et2O into a solution of 3a·H2O in CHCl3. Synthesis of [Pd{C,N-C(NXy)C(Ph)C(Ph)C6H2CH2CH2NH22,(OMe)2-4,5}Br(CNXy)] (4a). XyNC (48 mg, 0.367 mmol) was added to a suspension of complex A (100 mg, 0.092 mmol) in CH2Cl2 (20 mL), and the resulting solution was stirred for 30 min. The mixture was filtered through a plug of Celite, the filtrate was concentrated to ca. 1 mL, and Et2O (30 mL) was added. The suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and air-dried to afford complex 4a as a yellow solid. Yield: 121 mg, 0.184 mmol, 81%. Mp: 183 °C. Anal. Calcd for C42H42BrN2O2Pd (807.138): C, 62.50; H, 5.25; N, 5.21. Found: C, 62.31; H, 5.25; N, 5.21. IR (cm−1): ν(NH) 3453 br w, 3326 m, 3258 m; ν(CN) 2177 s; ν(CN) 1628 s. 1H NMR (400.91 MHz, −60 °C): δ 1.20 (s, 3 H, Me, Xy-inserted), 1.92 (m, 1 H, NH2), 2.23 (s, 6 H, Me, Xycoordinated), 2.48 (s, 3 H, Me, Xy-inserted), 2.65 (br d, 1 H, NH2, 3 JHH = 7.2 Hz), 3.21−3.33 (m, 2 H, 1 H of CH2Ar + 1 H of CH2N), 3.77−3.82 (m, partially obscured by the MeO signal, 1 H, CH2N), 3.78 (s, 3 H, MeO), 4.00 (s, 3 H, MeO), 4.14 (m, 1 H, CH2Ar), 6.45 (“t”, 1 H, p-H, Xy, 3JHH = 7.2 Hz), 6.74 (s, 1 H, H3), 6.79−6.83 (m, 2 H, m-H, Xy), 6.84 (s, 1 H, H6), 6.91−6.94 (m, 3 H, 2 H of o-H + 1 H of p-H, Ph), 6.98 (d, 2 H, m-H, Xy, 3JHH = 7.6 Hz), 7.03−7.31 (m, 7 H, 4 H of m-H + 2 H of o-H + 1 H of p-H, Ph), 7.71 (br d, 1 H, p-H, Xy, 3JHH = 7.2 Hz). 13C{1H} NMR (100.81 MHz, −60 °C): δ 16.3 (s, Me, Xy-inserted), 19.0 (s, Me, Xy-coordinated), 20.1 (s, Me, Xyinserted), 31.7 (s, CH2Ar), 44.9 (s, CH2N), 55.7 (s, MeO), 55.7 (s, MeO), 108.2 (s, CH, C6), 113.0 (s, CH, C3), 123.7 (s, p-CH, Ph), 125.1 (s, C1), 125.5 (s, i-C, Xy), 126.1 (s, o-C, Xy), 126.4 (s, p-CH, Xy), 127.3 (s, o-C, Xy), 127.4 (s, m-CH, Xy), 127.7 (s, m-CH, Xy), 127.7 (s, m-CH, Xy), 127.8 (s, p-CH, Xy), 127.9 (s, p-CH, Ph), 130.0 (s, o-CH, Ph), 132.8 (s, o-CH, Ph), 133.1 (s, C-Ar), 134.2 (s, o-C, Xy), 135.5 (s, C2), 136.9 (s, i-C, Xy), 140.5 (s, CN, Xy-coordinated), 141.4 (s, i-C, Ph), 144.9 (s, C-CN), 146.5 (s, i-C, Xy), 147.4 (s, C4), 148.2 (s, C5), 187.3 (s, CN, Xy-inserted). The 13C resonances corresponding to m-CH (Xy) and m-CH (Ph) were not observed. Single crystals of 4a·CHCl3·Et2O suitable for an X-ray diffraction study were obtained by slow diffusion of Et2O into a solution of 4a in CHCl3. Synthesis of 6a. TlTfO (61 mg, 0.173 mmol) was added to a suspension of complex 4a (140 mg, 0.173 mmol) in acetone (20 mL), and the resulting solution was stirred for 30 min. The mixture was filtered through a plug of Celite, the solvent was removed from the filtrate, and toluene (10 mL) was added. The mixture was heated at 110 °C for 16 h. Decomposition to metallic palladium was observed. The suspension was filtered through a plug of Celite, the solvent was removed from the filtrate, and the residue was vigorously stirred in Et2O (30 mL). The suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and air-dried to afford compound 6a as an orange solid. Yield: 80 mg, 0.143 mmol, 69%. Mp: 135 °C. ESIHRMS: exact mass calcd for C33H33N2O2 489.2542 [(M − TfO)+]; found 489.2542. ΛM (Ω−1 mol−1 cm2): 100 (5.0 × 10−4 M). IR (cm−1): ν(NH) 3175 br m; ν(CN) 1632 s. 1H NMR (300.1 MHz, acetone-d6): δ 1.54 (s, 3 H, Me, Xy), 2.11 (s, 3 H, Me, Xy), 3.15−3.26 (m, 1 H, CH2Ar), 3.58−3.69 (m, 1 H, CH2Ar), 3.73 (s, 3 H, MeO), 3.78−3.85 (m, partially obscured by the MeO signal, 1 H, CH2N), 3.83 (s, 3 H, MeO), 4.06−4.17 (m, 1 H, CH2N), 6.95 (s, 1 H, H10), 6.95 (s, 1 H, H7), 7.02−7.21 (m, 5 H, 2 H of o-H, Ph; 2 H of m-H + 1 H of p-H, Xy), 7.22−7.31 (m, 3 H, 2 H of m-H + 1 H of p-H, Ph), 7.38−7.42 (m, 3 H, 2 H of m-H + 1 H of p-H, Ph), 7.67−7.71 (m, 2 H, o-H, Ph), 8.41 (br s, 1 H, CH2NH), 10.83 (s, 1 H, XyNH). 13 C{1H} NMR (100.81 MHz, acetone-d6): δ 16.7 (s, Me, Xy), 18.1 (s, Me, Xy), 33.2 (s, CH2Ar), 42.4 (s, CH2N), 56.3 (s, MeO), 56.3 (s,

MeO), 114.5 (s, CH, C7), 115.5 (s, CH, C10), 128.3 (s, C10a), 129.0 (s, p-CH, Ph), 129.3 (s, p-CH, Ph), 129.5 (s, C-Me, Xy), 129.8 (s, mCH + m-CH, Ph), 130.0 (s, m-CH, Xy), 130.1 (s, m-CH, Xy), 130.6 (s, p-CH, Xy), 130.7 (s, C-Me, Xy), 131.1 (s, 129.4 (s, o-CH, Ph), 131.2 (s, o-CH, Ph), 133.7 (s, C6a), 135.0 (s, C5), 136.7 (s, i-C, Ph), 136.9 (s, i-C, Ph), 138.9 (s, C6), 149.5 (s, C8), 149.8 (s, C9), 151.2 (s, i-C, Xy), 173.6 (s, CO). Single crystals of 6a·Et2O suitable for an X-ray diffraction study were obtained by slow diffusion of Et2O into a solution of 6a in acetone. Synthesis of 7d. TlTfO (95 mg, 0.268 mmol) was added to a solution of (2d + 5d)·H2O (160 mg, 0.259 mmol) in acetone (15 mL), and the mixture was stirred for 1 h. The solvent was removed, toluene (20 mL) was added, and the mixture was refluxed for 8 h. Decomposition to metallic palladium was observed. The solvent was removed, CH2Cl2 (20 mL) was added, and the suspension was filtered through a plug of Celite. The solvent was concentrated to ca. 1 mL, and n-pentane (20 mL) was added. The suspension was filtered, and the solid was air-dried to give the crude amidinium salt 6d (123 mg, 0.203 mmol, 78%). 1H NMR (300.1 MHz): δ 1.27 (s, 3 H, Me, CMe2), 1.31 (s, 3 H, Me, CMe2), 1.40 (s, 3 H, Me, Xy), 2.21 (s, 3 H, Me, Xy), 2.92 (d, 1 H, CH2Ar, 2JHH = 13.8 Hz), 3.84 (d, 1 H, CH2Ar, 2 JHH = 13.8 Hz), 5.31 (s, 1 H, NH), 6.99−7.45 (m, 15 H, aromatic), 7.65−7.70 (m, 2 H, aromatic), 11.69 (s, 1 H, NH). Crude 6d was dissolved in CH2Cl2, Na2CO3 (200 mg, 1.88 mmol) was added, and the mixture was stirred for 12 h. The suspension was filtered, the solvent was removed, and the residue was stirred in n-pentane (30 mL). The suspension was filtered through a plug of Celite, and the solvent was removed from the filtrate to afford the amidine 7d as a pale yellow solid. Yield: 75 mg, 0.164 mmol, 81%. Mp: 156 °C. ESIHRMS: exact mass calcd for C33H33N2 457.2644 [(M + H)+]; found 457.2638. IR (cm−1): ν(NH) 3373 m; ν(CN) 1622 vs 1H NMR (400.91 MHz): δ 1.07 (s, 3 H, Me, CMe2), 1.17 (s, 3 H, Me, CMe2), 1.25 (s, 3 H, Me, Xy), 2.07 (s, 3 H, Me, Xy), 2.77 (d, 1 H, CH2Ar, 2JHH = 13.6 Hz), 3.78 (d, 1 H, CH2Ar, 2JHH = 13.2 Hz), 3.90 (s, 1 H, NH), 6.75 (t, 1 H, p-H, Xy, 3JHH = 7.4 Hz), 6.82 (br d, 1 H, m-H, Xy, 3JHH = 6.8 Hz), 6.94 (br d, 1 H, m-H, Xy, 3JHH = 7.2 Hz), 6.98 (m, 2 H, o-H, Ph), 7.07 (m, 3 H, Ph), 7.18−7.27 (m, 7 H, Ph and Ar), 7.86 (m, 2 H, o-H, Ph). 13C{1H} NMR (100.81 MHz): δ 16.4 (s, Me, Xy), 18.9 (s, Me, Xy), 30.6 (s, Me, CMe2), 32.0 (s, Me, CMe2), 45.1 (s, CH2Ar), 53.6 (s, CMe2), 122.4 (s, p-CH, Xy), 126.9 (s, CH, Ar), 127.1 (s, pCH, Ph), 127.3 (s, p-CH, Ph), 127.59 (s, CH, Ar), 127.62 (s, m-CH, both Ph), 128.0 (s, m-CH, Xy), 128.1 (s, m-CH, Xy), 129.0 (s, CH, C10), 129.1 (s, o-C, Xy), 129.5 (s, o-C, Xy), 130.2 (s, CH, C7), 130.7 (s, o-CH, Ph), 130.8 (s, o-CH, Ph), 135.9 (s, C5), 137.4 (s, C10a), 137.7 (s, C6 or i-C, Ph), 140.5 (s, i-C, Ph), 141.7 (s, C6 or i-C, Ph), 143.3 (s, C6a), 145.0 (br s, i-C, Xy), 154.3 (s, CN). Synthesis of 8a. CO was bubbled for 5 min through a suspension of palladacycle A (140 mg, 0.128 mmol) in MeOH (30 mL) in a Carius tube. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 48 h. Decomposition to metallic palladium was observed. The resulting suspension was filtered through a plug of Celite, and the solvent was removed from the filtrate. The residue was vigorously stirred in Et2O (30 mL), the yellow suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and airdried to afford a first crop of compound 8a as a yellow solid (56 mg). The filtrate was concentrated to ca. 2 mL, and n-pentane (20 mL) was added. The suspension was filtered, and the solid was washed with npentane (2 × 5 mL) and air-dried to afford a second crop of compound 8a as a yellow solid (15 mg). Yield: 71 mg, 0.142 mmol, 56%. Mp: 155 °C. ESI-HRMS: exact mass calcd for C26H28NO4 418.2018 [(M − Br)+]; found 418.2022. ΛM (Ω−1 mol−1 cm2): 71 (4.98 × 10−4 M). IR (cm−1): ν(NH) 3593 br w, 3550 br w, 3480 br w, 3413 br m; ν(CO) 1698 vs 1H NMR (300.1 MHz, DMSO-d6): δ 2.56−2.77 (m, 3 H, 2 H of CH2Ar + 1 H of CH2N), 2.87−3.04 (m, 1 H, CH2N), 3.42 (s, 3 H, MeO), 3.75 (s, 3 H, MeO), 3.78 (s, 3 H, MeO), 6.84 (s, 1 H, H6), 6.85 (s, 1 H, H3), 6.94−6.99 (m, 2 H, o-H Ph), 7.09−7.17 (m, 5 H, 2 H of o-H + 3 H of m-H, Ph), 7.21−7.25 (m, 3 H, 2 H of p-H + 1 H of m-H, Ph), 7.75 (br s, 3 H, NH3). 13C{1H} NMR (100.81 MHz, DMSO-d6): δ 30.3 (s, CH2Ar), 30.4 (s, CH2N), 51.8 (s, MeO), 55.4 (s, MeO), 55.8 (s, MeO), 113.2 (s, CH, C3), 27


Organometallics

Article

Synthesis of 8d. CO was bubbled for 5 min through a suspension of palladacycle D (150 mg, 0.160 mmol) in MeOH (10 mL) in a Carius tube. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 5 h. Decomposition to metallic palladium was observed. The suspension was filtered through a plug of Celite, the pale yellow filtrate was concentrated to ca. 1 mL, and Et2O (20 mL) was added. The resulting suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and air-dried to give 8d as a colorless solid. Yield: 116 mg, 0.275 mmol, 86%. Mp: 233 °C. ESIHRMS: exact mass calcd for C26H28NO2 386.2115 [(M − Cl)+]; found 386.2121. ΛM (Ω−1 mol−1 cm2): 103 (5.45 × 10−4 M). IR (cm−1): ν(NH) 3369 br; ν(CO) 1722 vs. 1H NMR (400.91 MHz): δ 1.45 (s, 3 H, Me, CMe2), 1.63 (s, 3 H, Me, CMe2), 2.44 (d, 1 H, CH2Ar, 2JHH = 14.4 Hz), 2.76 (d, 1 H, CH2Ar, 2JHH = 14.4 Hz), 3.55 (s, 3 H, MeO), 7.07−7.13 (m, 5 H, Ph or Ar), 7.16−7.18 (m, 3 H, Ph or Ar), 7.21−7.24 (m, 2 H, Ph or Ar), 7.27 (m, 1 H, H3), 7.37−7.39 (m, 3 H, Ph or Ar), 8.55 (br s, 3 H, NH3). 13C{1H} NMR (100.81 MHz): δ 25.9 (s, Me, CMe2), 27.8 (s, Me, CMe2), 43.4 (s, CH2Ar), 52.6 (s, MeO), 55.6 (s, CMe2), 127.6 (s, CH), 127.9 (s, CH), 128.2 (br s, CH), 128.4 (s, CH), 130.4 (s, CH), 130.6 (s, CH), 130.8 (s, CH), 133.7 (s, CH, C6), 133.9 (s, C1), 135.1 (s, C), 136.7 (s, C), 138.6 (s, C), 142.9, (s, C2), 148.9 (s, C), 172.0 (s, CO). Single crystals suitable for an X-ray diffraction study were obtained by slow diffusion of n-pentane into a solution of 8d in CH2Cl2. Synthesis of 8e,e′. CO was bubbled for 5 min through a suspension of palladacycle E (100 mg, 0.111 mmol) in MeOH (10 mL) in a Carius tube. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 2 h. Decomposition to metallic palladium was observed. The resulting black suspension was filtered through a plug of Celite, the filtrate was concentrated to ca. 1 mL, and Et2O (20 mL) was added. The suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and air-dried to afford the ester 8e as a colorless solid. Yield: 42 mg, 0.104 mmol, 47%. Mp: 95 °C. ESI-HRMS: exact mass calcd for C22H26NO4 368.1862 [(M − Cl)+]; found 368.1860. ΛM (Ω−1 mol−1 cm2): 9 (5.35 × 10−4 M). IR (cm−1): ν(NH) 3458 m, 3359 m, 3305 m; ν(CO) 1728 vs, 1705 s. 1H NMR (300.1 MHz): δ 1.51 (s, 6 H, CMe2), 3.07 (br s, 2 H, CH2Ar), 3.47 (s, 3 H, MeO), 3.49 (s, 3 H, MeO), 7.28−7.43 (m, 9 H, Ar + Ph), 8.40 (br s, 3 H, NH3). 13C{1H} NMR (75.81 MHz): δ 25.8 (s, CMe2), 43.0 (s, CH2Ar), 52.4 (s, MeO), 52.5 (s, MeO), 56.4 (s, CMe2), 127.5 (s, CH, C4), 128.0 (s, o-CH or m-CH, Ph), 128.5 (s, o-CH or m-CH, Ph), 128.9 (s, CH), 129.2 (s, CH), 130.9 (s, CH), 132.3 (s, CH, C6), 133.8 (s, C), 135.2 (s, C), 136.2 (s, C2), 137.5 (s, C), 141.4 (s, C), 168.1 (s, CO), 168.2 (s, CO). When the mixture of palladacycle E and CO in MeOH was stirred for 2 days, or when a solution of the isolated salt 8e was stirred at room temperature for 2 days or heated at 65 °C for 12 h, a mixture of isomers 8e and 8e′ in a 1/5 ratio was obtained. NMR data of the salt 8e′ extracted from the mixture are as follows. 1H NMR (300.1 MHz): δ 1.28 (s, 3 H, Me, CMe2), 1.40 (s, 3 H, Me, CMe2), 2.42 (d, 1 H, CH2Ar, 2JHH = 13.8 Hz), 2.78 (d, 1 H, CH2Ar, 2JHH = 14.1 Hz), 3.75 (s, 3 H, MeO), 3.86 (s, 3 H, MeO), 7.04−7.28 (m, 9 H, Ar + Ph), 8.40 (br s, 3 H, NH3). 13C{1H} NMR (75.81 MHz): δ 25.0 (s, Me, CMe2), 26.2 (s, Me, CMe2), 42.3 (s, CH2Ar), 52.79 (s, MeO), 52.84 (s, MeO), 56.0 (s, CMe2), 127.2 (s, CH, Ar), 128.2 (s, o-CH or m-CH, Ph), 129.0 (s, CH), 129.1 (br s, o-CH or m-CH, Ph), 131.5 (s, CH), 132.4 (s, CH), 132.7 (s, C), 132.8 (s, C), 133.6 (s, C1), 134.5 (s, C), 143.9 (s, C), 167.8 (s, CO), 168.8 (s, CO). Synthesis of 8f. CO was bubbled for 5 min through a solution of palladacycle F (130 mg, 0.160 mmol) in MeOH (10 mL) in a Carius tube. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 5 h. Decomposition to metallic palladium was observed. The suspension was filtered through a plug of Celite, the solvent was removed from the filtrate, and Et2O (3 mL) and n-pentane (20 mL) were added. The resulting suspension was filtered, and the solid was washed with n-pentane (2 × 5 mL) and airdried to afford 8f as a colorless solid. Yield: 106 mg, 0.294 mmol, 92%. Mp: 190 °C. ESI-HRMS: exact mass calcd for C21H26NO2 324.1964 [(M − Cl)+]; found 324.1963. ΛM (Ω−1 mol−1 cm2): 10 (6.00 × 10−4 M). IR (cm−1): ν(NH) 3486 br; ν(CO) 1733 s. 1H NMR (400.91

113.4 (s, CH, C6), 127.5 (s, C1), 127.7 (s, p-CH, Ph), 127.8 (s, p-CH, Ph), 127.8 (s, m-CH, Ph), 128.3 (s, m-CH, Ph), 129.5 (s, o-CH, Ph), 129.8 (s, o-CH, Ph), 133.0 (s, C2), 134.5 (s, C-CO), 136.3 (s, i-C, Ph), 139.0 (s, i-C, Ph), 144.4 (s, C-Ar), 147.1 (s, C4), 148.5 (s, C5), 169.3 (s, CO). Single crystals suitable for an X-ray diffraction study were obtained by slow diffusion of Et2O into a solution of 8a in MeOH. Synthesis of 8b. CO was bubbled for 5 min through a suspension of palladacycle B (see note below; 80 mg, 0.079 mmol) in MeOH (30 mL) in a Carius tube. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 16 h. Decomposition to metallic palladium was observed. The resulting suspension was filtered through a plug of Celite, the solvent was removed from the filtrate, and the residue was vigorously stirred in Et2O (30 mL). The suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and dried under nitrogen to afford 8b as a cream-colored solid. Yield: 50 mg, 0.104 mmol, 66%. Mp: 110 °C. ESI-HRMS: exact mass calcd for C22H26NO6 400.1760 [(M − Br)+]; found 400.1764. ΛM (Ω−1 mol−1 cm2): 22 (3.33 × 10−4 M). IR (cm−1): ν(NH) 3695 br w, 3597 br w; ν(CO) 1721 m. 1H NMR (400.91 MHz): δ 3.09−3.15 (m, 2 H, CH2Ar), 3.50−3.55 (m, 2 H, CH2N), 3.54 (s, 3 H, MeO), 3.58 (s, 3 H, MeO), 3.86 (s, 3 H, MeO), 3.99 (s, 3 H, MeO), 6.71 (s, 1 H, H3), 7.01 (s, 1 H, H6), 7.33−7.44 (m, 5 H, o-H + m-H + p-H, Ph), 7.87 (br s, 3 H, NH3). 13C{1H} NMR (75.45 MHz): δ 30.4 (s, CH2Ar), 39.2 (s, CH2N), 52.6 (s, MeO), 52.6 (s, MeO), 53.0 (s, MeO), 56.1 (s, MeO), 56.3 (s, MeO), 112.6 (s, CH, C3), 114.2 (s, CH, C6), 126.3 (s, C1), 127.2 (s, C2), 127.9 (s, o-CH, Ph), 128.6 (s, m-CH, Ph), 129.2 (s, p-CH, Ph), 134.1 (s, C-Ar), 136.9 (s, i-C, Ph), 141.5 (s, C-CO), 148.2 (s, C4), 149.7 (s, C5), 167.9 (s, CO), 168.8 (s, CO). Note: the starting material is actually a 2.5/1 mixture of palladacycle B and its regioisomer B′, which differs in the position of the substituents in the alkenyl moiety.18 Therefore, compound 8b is isolated along with a small amount of its corresponding regioisomer 8b′ (ratio 8b/8b′ = 3.5/1, by 1H NMR). Selected data for 8b′ are as follows. 1H NMR (400.91 MHz): δ 3.70 (s, 3 H, MeO), 3.71 (s, 3 H, MeO), 3.87 (s, 3 H, MeO), 3.99 (s, partially obscured by the MeO signal, 3 H, MeO), 6.72 (s, 1 H, H3), 7.11 (s, 1 H, H6). 13C{1H} NMR (75.45 MHz): δ 52.5 (s, MeO), 53.1 (s, MeO), 56.2 (s, MeO), 56.4 (s, MeO), 111.1 (s, CH, C3), 115.5 (s, CH, C6). Synthesis of 8c. CO was bubbled for 5 min through a suspension of palladacycle C (see note below; 100 mg, 0.103 mmol) in MeOH (30 mL) in a Carius tube. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 16 h. Decomposition to metallic palladium was observed. The suspension was filtered through a plug of Celite, the solvent was removed from the filtrate, and the residue was vigorously stirred in Et2O (30 mL). The resulting suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and dried under nitrogen to afford 8c as a cream-colored solid. Yield: 50 mg, 0.115 mmol, 55%. Mp: 128 °C. ESI-HRMS: exact mass calcd for C21H26NO4 356.1862 [(M − Br)+]; found 356.1875. ΛM (Ω−1 mol−1 cm2): 15 (3.94 × 10−4 M). IR (cm−1): ν(NH) 34814 br m; ν(CO) 1717 vs. 1H NMR (400.91 MHz): δ 1.98 (m, 3 H, Me), 3.06 (m, 1 H, CH2Ar), 3.14 (m, 1 H, CH2Ar), 3.39−3.44 (m, 1 H, CH2N), 3.52 (s, 3 H, MeO), 3.39−3.44 (m, partially obscured by the MeO signal, 1 H, CH2N), 3.85 (s, 3 H, MeO), 3.96 (s, 3 H, MeO), 6.54 (s, 1 H, H3), 6.99 (s, 1 H, H6), 7.37−7.45 (m, 5 H, 2 H of o-H + 2 H of m-H + 1 H of p-H, Ph), 7.97 (br s, 3 H, NH3). 13C{1H} NMR (100.81 MHz): δ 22.6 (s, Me), 30.2 (s, CH2Ar), 40.3 (s, CH2N), 52.6 (s, MeO), 56.1 (s, MeO), 56.2 (s, MeO), 110.8 (s, CH, C3), 113.7 (s, CH, C6), 124.3 (s, C1), 128.0 (s, p-CH, Ph), 128.6 (s, m-CH, Ph), 129.6 (s, o-CH, Ph), 134.6 (s, C-CO), 134.9 (s, C2), 135.5 (s, i-C, Ph), 146.6 (s, C-Ar), 148.4 (s, C4), 148.8 (s, C5), 170.5 (s, CO). Note: the starting material is actually a 5/1 mixture of palladacycle C and its regioisomer C′, which differs in the position of the substituents in the alkenyl moiety.18 Therefore, compound 8c is isolated along with a small amount of its corresponding regioisomer 8c′ (ratio 8/8c′ = 8/ 1, by 1H NMR). Selected data for 8c′ are as follows. 1H NMR (400.91 MHz): δ 2.20 (m, 3 H, Me), 3.64 (s, 3 H, MeO), 3.89 (s, 3 H, MeO), 3.92 (s, 3 H, MeO), 6.66 (s, 1 H, H3), 6.85 (s, 1 H, H6). 28


Organometallics

Article

MHz): δ 1.43 (s, 3 H, Me, CMe2), 1.65 (s, 3 H, Me, CMe2), 2.04 (s, 3 H, MeC), 2.98 (d, 1 H, CH2Ar, 2JHH = 14.0 Hz), 3.31 (d, 1 H, CH2Ar, 2JHH = 14.4 Hz), 3.40 (s, 3 H, MeO), 7.14 (m, 1 H, H3), 7.24−7.30 (m, 4 H, H4 + H5 + H6 + p-H from Ph), 7.36 (br t, 2 H, m-H, Ph, 3JHH = 7.6 Hz), 7.55 (br dd, 2 H, o-H, Ph, 3JHH = 8.0, 4JHH = 1.2 Hz), 8.61 (br s, 3 H, NH3). 13C{1H} NMR (75.45 MHz): δ 23.4 (s, MeC), 25.6 (s, Me, CMe2), 27.0 (s, Me, CMe2), 43.2 (s, CH2Ar), 52.1 (s, MeO), 56.1 (s, CMe2), 127.4 (s, CH, C4), 127.5 (s, CH, C5), 127.7 (s, p-CH, Ph), 128.3 (s, m-CH, Ph), 128.6 (s, CH, C3), 129.5 (s, o-CH, Ph), 132.0 (s, C1), 132.4 (s, CH, C6), 134.4 (s, C(CO2Me)), 136.1 (s, i-C, Ph), 143.7 (s, C2), 147.0 (s, MeC), 170.0 (s, CO). Synthesis of 9d. TlTfO (114 mg, 0.322 mmol) was added to a solution of palladacycle D (150 mg, 0.160 mmol) in acetone (15 mL) in a Carius tube. CO was bubbled through the resulting suspension for 5 min. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 12 h. Decomposition to metallic palladium was observed. The suspension was filtered through a plug of Celite, the filtrate was concentrated to ca. 1 mL, and n-pentane (20 mL) was added. The resulting suspension was filtered, and the solid was washed with n-pentane (2 × 5 mL) and air-dried to give crude 9d as a colorless solid. Yield: 131 mg, 0.251 mmol, 78.5%. The solid was recrystallized from acetone/Et2O (recrystallization yield: 47%). Dec pt: 163 °C. ESI-HRMS: exact mass calcd for C25H26NO2 372.1963 [(M − TfO)+]; found 372.1961. ΛM (Ω−1 mol−1 cm2): 127 (4.33 × 10−4 M). IR (cm−1): ν(NH) 3145 br s, 3078 br s; ν(CO) 1725 s, 1695 s. 1H NMR (300.1 MHz, acetone-d6): δ 1.43 (s, 3 H, Me, CMe2), 1.47 (s, 3 H, Me, CMe2), 2.68 2.75 (AB system, 2 H, 2JAB = 14.7 Hz), 7.02 (m, 2 H, o-H, Ph), 7.11 (m, 2 H, m-H, Ph), 7.15−7.18 (m, 3 H, o-H + p-H, Ph), 7.22−7.24 (m, 3 H, m-H + p-H, Ph), 7.38−7.49 (m, 3 H, H4 + H5 + H6, Ar), 7.58 (m, 1 H, H3, Ar), 7.88 (br s, 3 H, NH3). The signal corresponding to CO2H is not observed. 13C{1H} NMR (100.81 MHz): δ 25.1; 25.4 (s, Me, CMe2), 28.0; 28.1 (s, Me, CMe2), 43.39; 48.38 (s, CH2Ar), 56.99; 57.08 (s, CMe2), 128.6 (s, p-CH, Ph), 128.7 (s, m-CH, Ph), 128.8 (s, CH, C4), 129.0 (s, m-CH, Ph), 129.1 (s, p-CH, Ph), 129.4 (s, CH, C5), 131.0 (s, o-CH, Ph), 131.3 (s, o-CH, Ph), 131.7 (s, CH, C3), 134.5 (s, C1), 134.6 (s, CH, C6), 136.9 (s, C7 or C8), 137.7 (s, i-C, Ph), 139.7 (s, i-C, Ph), 143.6 (s, C2), 148.5 (s, C7 or C8), 174.2 (s, CO). The 13C NMR signals corresponding to the TfO group was not observed. The signals corresponding to CH2Ar and CMe2 appear duplicated, probably as a consequence of the strong hydrogen bond between the NH3 and CO2H groups, which leads to a nonfluxional conformation of the organic fragment. The 13C{1H} NMR spectrum was also recorded in DMSO-d6 (75.81 MHz): δ 24.9 (s, Me, CMe2), 42.2 (s, CH2Ar), 53.9 (s, CMe2), 120.6 (q, TfO, 1JCF = 332.8 Hz), 127.0 (s, CH + CH, Ar or p-CH from Ph), 127.2 (s, CH), 127.5 (s, CH), 127.6 (s, m-CH, Ph), 127.8 (s, m-CH, Ph), 129.5 (s, oCH, Ph), 130.0 (s, o-CH, Ph), 130.8 (s, CH, Ar), 132.7 (s, CH, Ar), 133.9 (s, C), 137.9 (br s, C), 139.6 (s, C), 142.6 (s, C), 171.6 (s, CO). The signals corresponding to two of the quaternary carbons were not observed. Single crystals of 9d·Me2CO, suitable for an X-ray diffraction study, were obtained by slow diffusion of n-pentane into a solution of 9d in acetone. Synthesis of 9e. TlTfO (98 mg, 0.277 mmol) was added to a solution of palladacycle E (120 mg, 0.134 mmol) in acetone (15 mL) in a Carius tube. CO was bubbled through the resulting suspension for 5 min. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 12 h. Decomposition to metallic palladium was observed. The suspension was filtered through a plug of Celite, the solvent was removed from the filtrate, and CHCl3 (1 mL) and Et2O (20 mL) were added to the residue. The suspension was filtered, the solvent was removed from the filtrate, n-pentane (20 mL) was added, and the mixture was vigorously stirred. The suspension was filtered, the solvent was removed from the filtrate, and the residue was vacuum-dried to give the ammonium triflate 9e as a very hygroscopic colorless solid. Yield: 96 mg, 0.190 mmol, 71%. Mp: 78 °C. ESIHRMS: exact mass calcd for C21H24NO4 354.1705 [(M − TfO)+]; found 354.1706. ΛM (Ω−1 mol−1 cm2): 116 (5.96 × 10−4 M). IR (cm−1): ν(NH) 3487 br m; ν(CO) 1722 br s, 1622 br s. 1H NMR (400.91 MHz): δ 1.30 (br s, 3 H, Me, CMe2), 1.43 (br s, 3 H, Me, CMe2), 2.90 (br m, 2 H, CH2Ar), 3.46 (s, 3 H, MeO), 6.90 (br s, 3 H,

NH3), 7.22 (d, 1 H, Ar, 3JHH = 7.6 Hz), 7.30−7.37 (m, 8 H, Ar + Ph), 7.90 (s, 1 H, OH). 13C{1H} NMR (75.81 MHz): δ 25.5 (s, Me, CMe2), 26.9 (s, Me, CMe2), 42.9 (s, CH2Ar), 52.6 (s, MeO), 56.6 (s, CMe2), 119.7 (q, CF3SO3, 1JCF = 323.7 Hz), 128.2 (s, o-CH or m-CH, Ph), 128.4 (s, CH), 128.5 (s, o-CH or m-CH, Ph), 129.2 (s, CH), 129.6 (s, CH), 131.1 (s, CH), 132.1 (s, CH), 132.7 (s, C), 134.4 (s, C), 135.9 (s, C), 138.5 (s, C), 141.3 (s, C), 168.3 (s, CO), 170.9 (s, CO). Synthesis of 9f. TlTfO (114 mg, 0.322 mmol) was added to a solution of palladacycle F (130 mg, 0.160 mmol) in acetone (15 mL) in a Carius tube. CO was bubbled through the resulting suspension for 5 min. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 12 h. Decomposition to metallic palladium was observed. The suspension was filtered through a plug of Celite, and the solvent was removed from the filtrate. The residue was dissolved in CH2Cl2 (2 mL), and Et2O was (20 mL) was added. The resulting suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and air-dried to give the salt 9f as a colorless solid. Yield: 78 mg, 0.169 mmol, 53%. Mp: 234 °C. ESI-HRMS: exact mass calcd for C20H24NO2 310.1802 [(M − TfO)+]; found 310.1808. ΛM (Ω−1 mol−1 cm2): 124 (4.95 × 10−4 M). IR (cm−1): ν(NH) 3125 br s; ν(CO) 1685 (s). 1H NMR (300.1 MHz, acetone-d6): δ 1.44 (s, 3 H, Me, CMe2), 1.63 (s, 3 H, Me, CMe2), 2.08 (s, 3 H, MeC), 3.13 (d, 1 H, CH2Ar, 2JHH = 14.7 Hz), 3.32 (d, 1 H, CH2Ar, 2JHH = 14.7 Hz), 7.25 (m, 1 H, H3), 7.30−7.45 (m, 8 H, Ar + Ph), 7.75 (br s, partially obscured by the resonance of NH3 group, 1 H, CO2H), 7.90 (br s, 3 H, NH3). 13C{1H} NMR (75.81 MHz, acetone-d6): δ 23.2 (s, MeC), 25.1 (s, Me, CMe2), 28.0 (s, Me, CMe2), 43.5 (s, CH2Ar), 57.1 (s, CMe2), 128.4 (s, CH), 128.5 (s, CH), 128.7 (s, CH), 129.1 (s, m-CH or o-CH, Ph), 129.4 (s, CH), 130.1 (s, m-CH or o-CH, Ph), 132.9 (s, C1), 133.9 (s, CH, C6), 136.1 (s, C(CO2H)), 137.0 (s, i-C, Ph), 144.5 (s, C2), 147.0 (s, MeC), 173.1 (s, CO). The 13C resonance corresponding to the CF3 group was not observed. Single crystals suitable for an X-ray diffraction study were obtained by slow diffusion of n-pentane into a solution of 9f in CHCl3. Synthesis of 10g. TlTfO (96 mg, 0.273 mmol) was added to a suspension of palladacycle G (100 mg, 0.136 mmol) in acetone (30 mL) in a Carius tube. CO was bubbled through the resulting suspension for 5 min. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 16 h. Decomposition to metallic palladium was observed. The suspension was filtered through a plug of Celite, the solvent was removed from the filtrate, and the residue was vigorously stirred in CH2Cl2 (30 mL). The resulting suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and air-dried to afford compound 10g as an orange solid. Yield: 66 mg, 0.176 mmol, 65%. Mp: 175 °C. ESI-HRMS: exact mass calcd for C11H16NO4 226.1076 [(M − TfO)+]; found 226.1082. ΛM (Ω−1 mol−1 cm2): 131 (8.50 × 10−4 M). IR (cm−1): ν(NH) 3484 br w; 3177 br m; ν(CO) 1683 vs 1H NMR (400.91 MHz, DMSO-d6): δ 3.03 (br m, 2 H, CH2N), 3.17 (m, 2 H, CH2Ar), 3.76 (s, 3 H, MeO), 3.83 (s, 3 H, MeO), 6.89 (s, 1 H, H6), 7.43 (s, 1 H, H3), 7.70 (br s, 3 H, NH3), 12.79 (s, 1 H, OH). 13C{1H} NMR (100.81 MHz, DMSO-d6): δ 31.7 (s, CH2Ar), 40.1 (s, CH2N), 55.5 (s, MeO), 55.6 (s, MeO), 113.8 (s, CH, C3), 114.6 (s, CH, C6), 121.5 (s, C2), 132.9 (s, C1), 146.9 (s, C4), 151.6 (s, C5), 167.8 (s, CO). Synthesis of 10h. TlTfO (183 mg, 0.518 mmol) was added to a solution of palladacycle H (150 mg, 0.258 mmol) in acetone (20 mL) in a Carius tube. CO was bubbled through the resulting suspension for 5 min. The pressure of CO was increased to 1 atm, the tube was sealed, and the mixture was stirred for 24 h. Decomposition to metallic palladium was observed. The suspension was filtered through a plug of Celite, the solvent was removed from the filtrate, and Et2O (2 mL) and n-pentane (25 mL) were added. The resulting suspension was filtered, and the solid was washed with n-pentane (2 × 5 mL) and airdried to give the salt 10h as a colorless solid. Yield: 162 mg, 0.472 mmol, 91%. Mp: 198 °C. ESI-HRMS: exact mass calcd for C11H16NO2 194.1181 [(M − TfO)+]; found 194.1179. ΛM (Ω−1 mol−1 cm2): 125 (6.4 × 10−4 M). IR (cm−1): ν(NH) 3237 br, 3107 br; ν(CO) 1698 vs. 1 H NMR (400.91 MHz, DMSO-d6): δ 1.15 (s, 6 H, CMe2), 3.34 (s partially obscured by the resonance of H2O from solvent, 2 H, 29


Organometallics

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CH2Ar), 7.30 (d, 1 H, H3, 3JHH = 7.6 Hz), 7.40 (t, 1 H, H5, 3JHH = 7.6 Hz), 7.53 (t, 1 H, H4, 3JHH = 7.6 Hz), 7.79 (br s, 3 H, NH3), 7.84 (d, partially obscured by the resonance of NH3, 1 H, H6, 3JHH = 8.0 Hz). 13 C{1H} NMR (100.81 MHz, DMSO-d6): δ 25.0 (s, CMe2), 41.2 (s, CH2Ar), 54.4 (s, CMe2), 120.6 (q, CF3, 1JCF = 322.2 Hz), 127.3 (s, CH, C5), 130.4 (s, CH, C6), 131.5 (s, CH, C4), 132.1 (s, C1), 133.1 (s, CH, C3), 135.5 (s, C2), 169.3 (s, CO). Synthesis of 11d. KtBuO (100 mg, 0.818 mmol) was added to a solution of palladacycle D (80 mg, 0.085 mmol) in dry toluene (10 mL) under a nitrogen atmosphere, in a Carius tube. The mixture was heated to 110 °C for 3.5 h. Decomposition to metallic palladium was observed. The solvent was removed from the filtrate, and Et2O (2 mL) and n-pentane (15 mL) were added. The resulting suspension was filtered through a plug of Celite, and the solvent was removed from the filtrate. The oily residue was dissolved in CH2Cl2 (5 mL), and HTfO (0.025 mL, 0.283 mmol) was added. The solution was stirred for 30 min and concentrated to ca. 1 mL, and Et2O (20 mL) was added. The suspension was filtered, and the solid was washed with Et2O (2 × 5 mL) and air-dried to give the salt 11d as a pale yellow solid. Yield: 16 mg, 0.034 mmol, 20%. Mp: 260 °C. ESI-HRMS: exact mass calcd for C24H24N 326.1909 [(M − TfO)+]; found 326.1912. ΛM (Ω−1 mol−1 cm2): 124 (5.37 × 10−4 M). 1H NMR (400.91 MHz, acetone-d6): δ 1.55 (s, 6 H, CMe2), 3.30 (s, 2 H, CH2Ar), 6.92 (d, 1 H, H6, 3JHH = 7.6 Hz), 7.05 (br d, 2 H, o-H, Ph, 3JHH = 6.8 Hz), 7.22−7.27 (m, 3 H, m-H + p-CH, Ph), 7.33−7.37 (m, 4 H, H7 + m-H + p-CH of Ph), 7.47 (br t, 1 H, H8, 3JHH = 7.6 Hz), 7.55−7.58 (m, 3 H, H9 + o-CH of Ph), 9.05 (br s, 2 H, NH2). 13C{1H} NMR (100.75 MHz, acetone-d6): δ 23.2 (s, CMe2), 42.5 (s, CH2Ar), 77.3 (s, CMe2), 120.6 (q, CF3, 1JCF = 320.1 Hz), 127.6 (s, CH, C7), 127.7 (s, CH, Ph), 127.9 (s, CH, Ph), 128.3 (s, CH, Ph), 128.9 (s, CH, Ph), 129.3 (s, CH, C8), 129.7 (s, CH, Ph), 130.0 (s, CH, C9), 130.4 (s, CH, Ph), 130.5 (s, CH, C6), 134.0 (s, C, Ph), 135.5 (s, C9a), 137.4 (s, C5a), 137.7 (s, C, Ph), 140.8 (s, C5). The resonance corresponding to C4 was not observed. Single crystals suitable for an X-ray diffraction study were obtained by slow diffusion of n-pentane into a solution of 11d in acetone. Single-Crystal X-ray Structure Determinations. Relevant crystallographic data, details of the refinements, a complete set of Cartesian coordinates, details (including symmetry operators) of hydrogen bonds, and CIF files for compounds 1a, 1d·1/2CHCl3, 1e·1/5H2O, 3a·1/2Et2O, 4a·CHCl3·Et2O, 5d, 6a·Et2O, 8a, 8d, 9d· Me2CO, 9f and 11d are given in the Supporting Information. Data Collection. For compounds 1a, 1d·1/2CHCl3, 1e·1/5H2O, 3a·1/2Et2O, 4a·CHCl3·Et2O, 6a·Et2O, 8a,d, 9d·Me2CO, 9f, and 11d, crystals suitable for X-ray diffraction were mounted in inert oil on a glass fiber and transferred to a Bruker SMART diffractometer. Data were recorded at 100(2) K, using graphite-monochromated Mo Kα radiation (λ = 0.71073 Å) and ω-scan mode. Multiscan absorption corrections were applied for all complexes. For complex 5d, crystals suitable for X-ray diffraction were mounted on loop fibers and transferred to a Bruker D8 QUEST diffractometer. Data were recorded at 100(2) K, using multilayer-monochromated Mo Kα radiation (λ = 0.71073 Å) and ω- and ϕ-scan modes. Multiscan absorption correction was applied. Structure Solution and Refinement. Crystal structures were solved by direct methods, and all non-hydrogen atoms were refined anisotropically on F2 using the program SHELXL-97.59 Hydrogen atoms were refined as follows. Compounds 1a, 1d·1/2CHCl3, 1e·1/5H2O, 3a·1/2Et2O, 4a·CHCl3·Et2O, 5d, 8a,d, 11d: NH2 or NH3, free with SADI; methyl, rigid group; all others, riding. Compound 6a·Et2O: NH, free; methyl, rigid group; all others, riding. Compound 9d·Me2CO: NH3 and OH, free; ordered methyls, rigid group; all others, riding. Compound 9f: NH3 and OH, free with SADI; methyl, rigid group; all others, riding. Special Features. For 1d·1/2CHCl3, the half-molecule of chloroform is disordered over an inversion center. For 1e·1/5H2O, the largest feature of residual electron density was a solitary peak (2.66 e Å3), disordered over an inversion center. This peak was arbitrarily assigned as water oxygen. It was refined isotropically and the occupation factor was allowed to vary (it refined to 0.4). Its hydrogens were not included in the refinement. For 3a·1/2Et2O, 4a·CHCl3·Et2O, and 5d, for each

compound, a region of residual electron density could not be interpreted in terms of realistic solvent molecules, even allowing for possible disorder. For this reason the program SQUEEZE, which is part of the PLATON system,60 was employed to remove mathematically the effects of the solvent. Standard deviations of refined parameters should be interpreted with caution. The void volumes per cell were 28 Å3 (3a·1/2Et2O), 884 Å3 (4a·CHCl3·Et2O), and 560 Å3 (5d) with void electron counts per cell of 6 (3a·1/2Et2O), 178 (4a· CHCl3·Et2O), and 117 (5d). These solvents were not taken into account when calculating derived parameters such as the formula weight, because the nature of the solvents was uncertain. For 9d· Me2CO, the acetone molecule is disordered over two positions with a ca. 57/43 occupancy distribution. Computational Details. Density funtional calculations were carried out using the Gaussian 03 package.61 The hybrid density functional BP8662 was applied, employing the SDD basis set63 to describe the Br, P, and Pd atoms and 6-31G* for N, C, O, and H.64 After geometry optimizations, analytical frequency calculations were carried out to determine the nature of the stationary points found and confirm they were minima.

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ASSOCIATED CONTENT

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AUTHOR INFORMATION

S Supporting Information *

Tables, figures, and CIF files giving Cartesian coordinates (Å), absolute energies (au) of computed structures, crystal data, structure refinement details, hydrogen bond data and crystallographic data for compounds characterized by XRD, X-ray thermal ellipsoid plots of complexes 1a, 1d·1/2CHCl3, 1e·1/5H2O, 3a·1/2Et2O, and 8d, and 1H and 13C APT spectra of organic compounds. This material is available free of charge via the Internet at http://pubs.acs.org Corresponding Author

*E-mail: [email protected] (I.S.-L.); [email protected] (J.V.). Web: http:// www.um.es/gqo/. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the Ministerio de Educación y Ciencia (Spain), FEDER (CTQ2011-24016), and Fundación Séneca (04539/ GERM/06) for financial support. J.-A.G.-L. and M.-J.O.-M. are grateful to the Fundación Séneca (CARM, Spain) and Ministerio de Educación y Ciencia (Spain), respectively, for their research grants.

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REFERENCES

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Organometallics

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