Article pubs.acs.org/Organometallics
Chelated Assisted Metal-Mediated N−H Bond Activation of β‑Lactams: Preparation of Irida‑, Rhoda‑, Osma‑, and Ruthenatrinems Luis Casarrubios,† Miguel A. Esteruelas,*,‡ Carmen Larramona,‡ Jaime G. Muntaner,† Montserrat Oliván,† Enrique Oñate,‡ and Miguel A. Sierra*,† †
Departamento de Quı ́mica Orgánica, Facultad de Ciencias Quı ́micas, Universidad Complutense, 28040 Madrid, Spain Departamento de Quı ́mica Inorgánica, Instituto de Sı ́ntesis Quı ́mica y Catálisis Homogénea (ISQCH), Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain
‡
S Supporting Information *
ABSTRACT: 2-Azetidinones substituted with pyridine (2a), quinoline (2b), isoquinoline (2c), imidazole (2d), and benzimidazole (2e) at the 4-position of the four-membered ring have been prepared in order to synthesize tribactams containing a transition metal and its associated ligands, LnM, at the 2-position of the tricyclic skeleton. The developed procedure is compatible with a wide range of transition-metal starting complexes. Thus, the iridium and rhodium dimers [M(η5-C5Me5)Cl2]2 react with 2a−e, in the presence of sodium acetate, to afford irida- and rhodatrinems (1a−j) containing the half-sandwich d6 metal fragments M(η5-C5Me5)Cl (M = Ir, Rh). The reactions of [M(μ-OMe)(η4-COD)]2 (M = Ir, Rh) with 2a lead to irida- and rhodatrinems (1k,l) with the d8 moieties M(η4-COD). The coordination sphere and oxidation state of the metal center in these compounds can be modified, without affecting the 2-azetidinone backbone, by means of substitution and oxidative addition reactions. As a proof of concept, metallatrinems with the M(CO)2 (M = Ir (1m), Rh (1n)) and Ir(Me)I(CO)2 (1o) units are also reported. Osmatrinems 1p,q containing the d4 metal fragment OsH3(PiPr3)2 have been obtained starting from the d2 hexahydride OsH6(PiPr3)2, by reaction with 2a,b, whereas the treatment of the tetrahydroborate complexes MH(η2-H2BH2)(CO)(PiPr3)2 (M = Os, Ru) with 2a yields osma- and ruthenatrinems (1r,s) containing six-coordinate bis(phosphine) d6 metal fragments. The IR stretching frequency of the lactamic carbonyl, the bent angle between the five- and four-membered rings of the tricycle, and the N−CO bond length in the lactamic ring are clearly infuenced by the LnM fragment.
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by far the most efficient is the use of β-lactamases.5 These enzymes catalyze the irreversible hydrolysis of the amide bond of the β-lactam ring, yielding the antibiotic inactive. Several classes of β-lactamases have been characterized, leading to the clinical answer of using the combination of the active β-lactam antibiotic and one agent to inactivate the hydrolytic enzyme.6 Tricyclic β-lactams known as tribactams or trinems7 are among the more promising candidates to act as β-lactamase inhibitors. Nevertheless, these inhibitors have a skeleton closely related to the natural and synthetic β-lactam antibiotics, which make them potential targets for the evolution of new βlactamases. Therefore, a drastically different approach to the problem is required. The incorporation of a transition metal8 and its associated ligands as a constituent of the tribactam skeleton is certainly a promising alternative. In this context, it should be noted that there are no analogues in nature and the metal fragment can afford a wide electronic and structural diversity, as a result of the wide range of coordination numbers and polyhedrons of the derivatives of these elements, which can
INTRODUCTION The neverending fight of mankind with bacteria has taken advantage of the evolutionary arsenal provided by fungi (one of the natural enemies of the bacteria) in the form, among others, of β-lactam antibiotics.1 However, the evolutionary pressure derived from the indiscriminate use of such as antibacterial agents has resulted in the apparition of bacteria strains capable of resisting the action, not only of the commonly used antibiotics but also of many of their synthetic analogues.2 In fact, several opinions have appeared pointing that humanity is losing its battle against these pathogens.3 Response to this situation follows two main trends. The first one is to prepare new antibacterial agents able to keep their activity in the presence of bacteria resistant to the already inactive antibacterial agents. The second front is to develop novel compounds to inactivate the mechanisms through which bacteria render useless the antibiotics. Both lines of action are a worldwide priority, since bacterial resistance is reaching unseen levels not only in underdeveloped countries but also in first-world countries.4 Bacteria have evolved several strategies to quench the bactericide action of β-lactam antibiotics: the main one and © 2014 American Chemical Society
Received: February 13, 2014 Published: April 1, 2014 1820
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be further modified through specific reactions. In addition, a plethora of useful starting complexes are available as metal precursors. The electronic and structural diversity introduced by the metal fragment should allow these systems to be used not only as inhibitors of β-lactamases but also as active antibacterial agents. This paper shows the first metallatrinems, which include four-, six-, and seven-coordinate transition-metal derivatives of Ir(III), Rh(III), Ir(I), Rh(I), Os(IV), Os(II), and Ru(II) ions as a member of the tricyclic system.
Scheme 2
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RESULTS AND DISCUSSION Synthetic Strategy. The available electron density of an amidate group is mainly centered on the nitrogen atom. Due to its high basicity, metal ion hydrolysis often competes with nitrogen ion coordination.9 As a consequence, the formation of stable nitrogen-coordinated amidate transition-metal derivatives is rare, in particular when β-lactams are involved,10 although complexes containing ligands with this moiety as a substituent are known.11 The balance shifts to the metal ion coordination when one or more anchors occur so that favorable five- or sixmembered chelate rings can be formed.9,12 Keeping this in mind, we designed 2-azetidinones substituted at the 4-position with an aromatic nitrogen donor group, which should bring the N−H bond to an electrophilic metal center to promote its activation. These metal centers activate σ bonds in a heterolytic manner using an external base or alternatively a ligand with sufficiently basic free electron pairs or hydride.13 We planned a four-step procedure for the synthesis of metallatribactams 1 having a metal at the 2-position of the tricyclic skeleton, with the aim of developing a flexible and easy route to these compounds (Scheme 1). The incorporation of
of the PMP group occurred uneventfully with cerium(IV) ammonium nitrate (CAN) to yield N−H 2-azetidinones 2a−c in acceptable to good yields (Scheme 3). Oxidation of the Scheme 3
Scheme 1
heterocyclic nitrogen did not take place. Extensive decomposition of the starting materials to unknown mixtures of products was observed, however, when the reaction was tested with 2-azetidinones having five-membered heterocycles at the 4-position of the four-membered ring and an allyl group at the nitrogen (3d,e). For these cases, the deprotection methodology described by Alcaide and Almendros involving the sequential use of Grubbs carbene (isomerization) and RuCl3 (oxidation) was employed.14 Treatment of compounds 3d,e with Ru( CHPh)Cl2(PCy3)2 (5 mol % per mol of 2-azetidinone 3) yielded compounds 5a,b having the N-1 allyl bond isomerized to the methylvinyl moiety, which were subsequently oxidized (RuCl3/NaIO4) to the corresponding N−H 2-azetidinones 2d,e. Yields of this oxidation were poor, probably due to oxidation of the five-membered ring at the 4-position (Scheme 4). Irida- and Rhodatrinems Containing Six-Coordinate Half-Sandwich d6 Metal Fragments. The feasibility of the synthesis of the metallatrinems was initially checked by reacting the 2-azetidinone 2a with the dimers [M(η5-C5Me5)Cl2]2 (M = Ir, Rh), using conditions similar to those previously employed to promote the chelated assisted aryl C−H bond activation,15 which do not produce the fragmentation of the four-membered
the metal in the tricyclic skeleton 1 takes place by means of an assisted chelated heterolytic N−H bond activation of the 2azetidinones 2. These substrates were accessed by N-1 deprotection of β-lactams 3 prepared through a Staudinger cycloaddition between the appropriate imine 4 and phenoxyacetyl chloride. Preparation of 2-Azetidinones. Imines 4a−d (Scheme 2) were reacted with phenoxyacetyl chloride, in the presence of Et3N, at −78 °C in dichloromethane, yielding the corresponding 2-azetidinones 3a−d in good to excellent yields as single cis isomers.11e Imine 4e required a modification of the procedure, involving boiling toluene instead of dichloromethane at −78 °C. The corresponding 2-azetidinone 3e was obtained as a 1/4 cis/trans mixture in an overall 39% yield, from which trans-3e was separated to be isolated in 31% yield. Compounds 3a−e bear either a p-MeOC6H4 (PMP) (3a−c) group or an allyl substituent (3d,e) at N-1. The election of the N-1 protecting group was critical to perform the next step. The compatibility of the heterocycle at the 4-position with the method used to remove the N-1 group was the pivotal feature of the synthesis of the 2-azetidinones. Thus, oxidative removal 1821
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occupying three sites of a face, whereas the pyridylamidate moiety lies in the opposite site with a bite angle of 75.0(3)°. The separation between the iridium center and the amidic nitrogen atom of 1.989(9) Å (Ir−N(1)) is about 0.2 Å shorter than that between the metal and the pyridinic nitrogen atom (Ir−N(2) = 2.168(8) Å). Both bond lengths are consistent with those reported for N-arylpicolinamidate iridium(III) derivatives.17 The lactamic N(1)−C(1) and C(1)−O(1) distances of 1.428(14) and 1.222(13) Å, respectively, agree with those found in the scarce pure organic trinems characterized by X-ray diffraction analysis.16,18 Metallatrinems 1a,b exist in solution as 5/1 mixtures of the two pairs of diastereoisomers resulting from the chirality of the metal center and both CH carbon atoms of the lactamic fourmembered ring. The most noticeable spectroscopic feature of these compounds is the presence of a singlet at 175.8 ppm for 1a and 177.1 ppm for 1b in the 13C{1H} NMR spectra, in chloroform-d, corresponding to the lactamic carbonyl group of the major diastereoisomer, which appears shifted by about 9 ppm toward lower field with regard to that of 2a (167.2 ppm). In the IR spectra in chloroform, the lactamic ν(CO) absorption is observed at 1696 cm−1 for 1a and 1684 cm−1 for 1b, in this case shifted more than 77 cm−1 toward lower frequencies with regard to that of 2a (1761 cm−1). Having demonstrated that the labile four-membered ring of 2-azetidinone was compatible with the N-directed N−H activation, the scope of the reaction with regard to the substituents at the 4-position of the four-membered ring was studied next. Under the experimental conditions previously mentioned, azetidinones 2b,c with quinoline and isoquinoline substituents, respectively, react with the iridium and rhodium dimers to give the respective metallatrinems 1c−f (Scheme 6)
Scheme 4
ring. In contrast to the lactamic cleavage, the treatment of the dimers with 1.0 equiv of the 2-azetidinone, in the presence of 2.3 equiv of sodium acetate, in dichloromethane at room temperature for 12 h leads to the irida- and rhodatrinems 1a,b, which were isolated as yellow and brown solids in 93% and 90% yields, respectively (Scheme 5). Their formation can be rationalized as the heterolytic rupture of the N−H bond of 2a, by action of the external acetate base, according to our initial hypothesis. Scheme 5
Iridatrinem 1a was characterized by X-ray diffraction analysis. Figure 1 gives a drawing of the molecule. The structure proves
Scheme 6
Figure 1. ORTEP diagram of complex 1a (50% probability ellipsoids). Hydrogen atoms (except those of the lactamic ring) are omitted for clarity. Selected bond lengths (Å) and angles (deg): Ir−Cl(1) = 2.434(3), Ir−N(1) = 1.989(9), Ir−N(2) = 2.168(8), N(1)−C(1) = 1.428(14), C(1)−O(1) = 1.222(13); N(1)−Ir(1)−N(2) = 75.0(3).
in excellent yields (80−96%). The reactions of 2d,e, having five-membered heterocyclic rings at the 4-position of the fourmembered ring, with the metal dimers analogously lead to the tetracyclic (2d) and tricyclic (2e) 2-metalla-β-lactams 1g−j also in excellent yields (90−96%). In agreement with the case for 1a,b, the 13C{1H} NMR spectra in chloroform-d of these compounds contain singlets between 177.0 and 179.0 ppm due to the lactamic carbonyl group, whereas the ν(CO) absorptions in the IR spectra are observed in the range 1685−1703 cm−1. The reactions shown in Schemes 5 and 6 demonstrate that the
the formation of the tricyclic skeleton with a dihedral angle between the five-membered metallacycle and the fourmembered lactamic ring of 55.55°, which compares well with the related angle in allyl (4S,8S,9R)-10-[(E)-ethylidene]-4methoxy-11-oxo-1-azatricyclo[7.2.0.03,8]undec-2-ene-2-carboxylate (53.74°),16 the immediate synthetic precursor of the βlactamase inhibitor sodium (8R,9R)-10-[(E)-ethylidene]-4methoxy-11-oxo-1-azatricyclo[7.2.0.03,8]undec-2-ene-2-carboxylate (Lek157). The geometry around the metal center is close to octahedral, with the pentamethylcyclopentadienyl ligand 1822
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method being developed is amenable to prepare [4,5,6], [4,5,6,6], [4,5,5], and [4,5,5,6] C-2 metalla analogues of tribactams. Irida- and Rhodatrinems Containing Four-Coordinate d8 Metal Fragments: Modification of the Coordination Sphere and Oxidation State of the Metal Center. The square-planar iridium and rhodium dimers [M(μ-OMe)(η4COD)]2 (M = Ir, Rh; COD = 1,5-cyclooctadiene) are useful starting materials to introduce M(η4-COD) moieties at the 2position of a tricyclic β-lactam system. Treatment of these dimers with 1.0 equiv of 2a, in pentane, at room temperature for 4−6 h leads to the metallatrinems 1k,l, containing a fourcoordinate d8 metal fragment (Scheme 7), which were isolated
Figure 2. ORTEP diagram of complex 1m (50% probability ellipsoids). Hydrogen atoms (except those of the β-lactamic ring) are omitted for clarity. Selected bond lengths (Å) and angles (deg): Ir−N(1) = 2.111(4), Ir−N(2) = 2.028(4), N(2)−C(8) = 1.340(6), C(8)−O(1) = 1.235(5); N(1)−Ir−N(2) = 77.72(15).
Scheme 7
bite angle of 77.72(15)°. The separation between the iridium center and the amidic nitrogen atom N(2) of 2.028(4) Å compares well with that of 1a and is about 0.1 Å shorter than the separation between the metal and the pyridinic N(1) nitrogen atom of 2.111(4) Å. Interestingly, the N(2)−C(8) bond length of 1.340(6) Å is about 0.1 Å shorter than the related parameter of 1a (N(1)−C(1)), suggesting that the replacement of the Ir(η5-C5Me5)Cl fragment by the Ir(CO)2 unit produces a strength increase of the N−carbonyl bond within the four-membered lactamic ring. In contrast to the N(2)−C(8) distance, the C(8)−O(1) bond length of 1.235(5) Å is statistically identical with the related parameter of 1a. A noticeable feature of the structure is also the association of two molecules through an Ir(dz2)−Ir(dz2) interaction (Figure 3).20
as orange and bright yellow solids in 77% and 69% yields, respectively. Their formation can be rationalized as the pyridine-assisted heterolytic N−H bond activation of the four-membered ring of 2a promoted by the internal methoxy base, although homolytic N−H addition to the metal center, followed by reductive elimination of methanol, should not be totally ruled out, since the square-planar iridium(I) and rhodium(I) complexes have Lewis base character.19 As expected due to the bent nature of the tricyclic unit, four olefinic resonances at 5.71, 5.36, 3.68, and 3.61 ppm (1k) and 5.65, 4.69, 4.03, and 3.91 ppm (1l) in the 1H NMR spectra and at 67.8, 65.9, 63.6, and 62.2 ppm (1k) and 81.5, 79.9, 79.5, and 79.2 ppm (1l) in the 13C{1H} NMR spectra are characteristic for these compounds, in dichloromethane-d2, at room temperature. In agreement with the case for 1a−j, the 13C{1H} NMR spectra also show singlets at 172.6 (1k) and 174.5 ppm (1l) due to the lactamic carbonyl group, whereas the ν(CO) absorptions in the IR spectra are observed at 1687 (1k) and 1680 cm−1 (1l). The possibility of modifying the coordination sphere of the metal center of the tricycle was also explored. From a conceptual point of view, this should afford a general methodology to prepare metallatrinems with not only different metals but also β-lactams having the same metal with properties tunable by changes in its coordination sphere. As a proof of concept, we performed the substitution of the diolefin of 1k,l by CO. Bubbling this gas through dichloromethane solutions of the diolefinic species leads to the cis-dicarbonyl derivatives 1m,n, keeping the tricyclic skeleton unaltered (Scheme 7). These compounds were isolated as orange solids in 90% yields in both cases. Iridatrinem 1m was characterized by X-ray diffraction analysis. The structure (Figure 2) proves the tricyclic nature of the species, which displays a dihedral angle between the fivemembered metallacycle and the four-membered lactamic ring of 53.57°, similar to that of 1a. The coordination geometry around the iridium atom is almost square planar, with the metal 0.0822 Å out of the best plane defined by the Ir(1), N(1), N(2), C(15), and C(16) atoms. The main distortion of the idealized geometry is due to the pyridylamidate N(1)−Ir−N(2)
Figure 3. Association of two molecules of complex 1m through an Ir(dz2)−Ir(dz2) interaction (Ir−Ir = 3.1821(4) Å).
The resulting dimer shows an intermolecular metal−metal distance of 3.1821(4) Å, which compares well with that reported for the anion [Ir(Tcbiim)(CO)2]− (3.183(1) Å; Tcbiim = 4,4′,5,5′-tetracyano-2,2-biimidazolate).21 The carbonyl ligands of one molecule eclipse the polycyclic system of the other molecule, whereas the lactamic four-membered rings are disposed in an antiparallel manner. The IR and 13C{1H} NMR spectra of 1m,n, in dichloromethane-d2, at room temperature are consistent with the structure shown in Figure 2. As expected for the cis-dicarbonyl nature of the metal fragments, the IR spectra show two bands at 2061 and 1991 cm−1 for 1m and 2073 and 2007 cm−1 for 1n along with the lactamic ν(CO) absorption at 1706 cm−1 for 1m and 1705 cm−1 for 1n. In the 13C{1H} NMR spectra, the carbonyl ligands display singlets at 178.9 and 171.9 ppm for 1m and doublets at 186.8 (JC−Rh = 63.0 Hz) and 185.5 ppm (JC−Rh = 74.0 Hz) for 1n. The lactamic CO resonance appears at 173.8 ppm for 1m and 174.6 ppm for 1n. 1823
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which were isolated as white solids in 82% and 71% yields, respectively. Under the reaction conditions, the starting hexahydride undergoes the reductive elimination of molecular hydrogen to afford the unsaturated d 4 tetrahydride OsH4(PiPr3)2,25 which promotes the heterolytic N−H cleavage of the lactam by the action of one of the hydride ligands. The resulting trihydride intermediates are stabilized by coordination of the nitrogen atom of the heterocyclic substituent at the 4position of the lactamic ring. The formation of 1p,q is new evidence of the wide versatility in coordination number, type of ligands, metal elements, and electronic and geometrical environments that it is possible to reach in the metal fragment of this novel type of tribactams through the synthetic methodology designed in Scheme 1. Osmatrinem 1p has been characterized by X-ray diffraction analysis. Figure 4 gives a drawing of the tricycle, which shows a
The tricyclic systems, including the lactamic four-membered ring, tolerate not only external and internal bases but also electrophilic reagents. As a consequence, it is possible to modify simultaneously the coordination sphere and the oxidation state of the metal center without affecting the sensitive 2-azetidinone backbone. Stirring of 1m in methyl iodide for 5 h at room temperature affords the six-coordinate iridium(III) derivative 1o, resulting from the SN2 oxidative addition of the alkyl halide to the iridium(I) center of the starting metallatrinem. Tricycle 1o was isolated as a white solid in 79% yield. In solution it exists as a 4/6 mixture of the diastereoisomers shown in Scheme 8. The presence of both species is strongly supported Scheme 8
by the 1H and 13C{1H} NMR spectra in dichloromethane-d2, at room temperature. The most noticeable feature in the 1H NMR spectrum is the presence of two singlets at 1.51 and 1.41 ppm, corresponding to the methyl ligand, which show a 4/6 intensity ratio. According to the proposed structures the 13C{1H} NMR spectrum contains four Ir−CO resonances at 163.5, 163.4, 158.4, and 158.3 ppm, in addition to the lactamic CO signals at 174.4 and 173.2 ppm and the methyl resonances at −10.2 and −12.0 ppm. Osmatrinems Containing a Seven-Coordinate d4 Metal Fragment: Hydride as Promoter of the N−H Bond Activation. The saturated hexahydride d2 complex OsH6(PiPr3)2 activates C−H bonds of a wide range of organic molecules.22 By protonation with weak Brønsted acids, it releases molecular hydrogen to afford osmium hydride d4 species which contain the corresponding conjugated base as a ligand.23 Furthermore, it has been recently shown that it also activates N−H bonds adjacent to a cyclic carbonyl group such as those of thymine, uracil, 1-methylthymine, 1-methyluracil, and cytosine.24 In agreement with this, the treatment of toluene solutions of this polyhydride with 1.0 equiv of 2a,b, under reflux, for 12 h leads to the osmatrinems 1p,q (Scheme 9),
Figure 4. ORTEP diagram of complex 1p (50% probability ellipsoids). Hydrogen atoms (except hydrides) are omitted for clarity. Selected bond lengths (Å) and angles (deg): Os−N(1) = 2.2062(8), Os−N(2) = 2.1218(19), N(2)−C(8) = 1.347(3), C(8)−O(2) = 1.223(3); P(1)−Os−P(2) = 163.08(2), N(1)−Os−N(2) = 73.70(7).
dihedral angle between the five-membered metallacycle and the four-membered lactamic ring significantly more closed (45.00°) than those of 1a,m. The geometry around the osmium atom can be rationalized as a distorted pentagonal bipyramid with the phosphine ligands occupying axial positions (P(1)−Os−P(2) = 163.08(2)°). The metal coordination sphere is completed by the pyridylamidate moiety, which in this case acts with a N(1)− Os−N(2) bite angle of 73.70(7)°, and the hydride ligands. The separation between the metal center and the amidic nitrogen atom N(2) of 2.1218(19) Å compares well with those reported for osmium amidate compounds26 and is about 0.08 Å shorter than the pyridinic Os−N(1) bond length of 2.2062(8) Å. The lactamic N(2)−C(8) and C(8)−O(2) distances of 1.347(3) and 1.223(3) Å, respectively, are statistically identical with the related parameters of 1m. Because of the bent nature of the tricyclic system, the phosphine ligands of the metal fragment are inequivalent. According to this, the 31P{1H} NMR spectra of 1p,q, in toluene, at room temperature show AB spin systems centered at 27.3 ppm in both cases and defined by Δν = 2873 Hz and JA‑B = 680 Hz (1p) and Δν = 1691 Hz and JA‑B = 670 Hz (1q). In the 1H NMR spectra at room temperature, the most noticeable feature is a hydride resonance at −11.72 ppm for 1p and at −11.70 ppm for 1q, which suggests the operation of two thermally activated site exchange processes for the inequivalent hydride ligands of each molecule. In agreement with this, the 1H{31P} NMR spectrum of 1p at 183 K contains
Scheme 9
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at −11.48 ppm an AB spin system, defined by Δν = 778 Hz and JA‑B = 77.5 Hz, and at −12.56 ppm a singlet (see the Supporting Information). The high value of the JA‑B coupling constant, for two cisoid disposed hydrides, indicates that HA and HB undergo quantum exchange coupling27 in addition to the thermally activated site exchange. Lactamic CO resonances at 175.2 ppm (1p) and 175.8 ppm (1q) in the 13C{1H} NMR spectra and ν(CO) bands at 1684 (1p) and 1681 cm−1 (1q) in the IR spectra are also characteristic of these compounds. Osma- and Ruthenatrinems Containing Six-Coordinate Bis(phosphine) d6 Metal Fragments: Tetrahydroborate Complexes as Introducers of the Metal Fragment. Complexes containing a tetrahydroborate ligand attached to the metal through two bridging hydrogen atoms are known for the most of the transition metals.28 In solution, they are in equilibrium with the M(η1-H-BH3) species, resulting from the breaking of a bridge.29 In agreement with this, most commonly BH3 is lost from the [BH4]− ligand, generating unsaturated hydride compounds. 30 The wide range of transition-metal tetrahydroborate complexes known and the fact proved in Scheme 9 that a hydride ligand promotes the heterolytic N−H bond activation of the lactam without affecting the four-membered ring prompted us to perform the reactions of the tetrahydroborate complexes MH(η2-H2BH2)(CO)(PiPr3)2 (M = Os, Ru)31 with 2a, in order to asseverate the wide versatility of the procedure. Treatment of toluene solutions of the aforementioned osmium and ruthenium tetrahydroborate compounds with 1.0 equiv of 2a, under reflux, for 12 h leads to the osma- and ruthenatrinems derivatives 1r,s (Scheme 10), containing six-
Figure 5. ORTEP diagram of complex 1s (50% probability ellipsoids). Hydrogen atoms (except the hydride) are omitted for clarity. Selected bond lengths (Å) and angles (deg): Ru−N(1) = 2.117(2), Ru−N(2) = 2.247(2), N(1)−C(1) = 1.350(3), C(1)−O(1) = 1.229(3); P(1)−RuP(2) = 162.33(2), N(1)−Ru−N(2) = 75.11(8), H(01)−Ru−N(2) = 169.4(10), C(15)−Ru−N(1) = 176.50(10).
occupying trans positions (P(1)−Ru−P(2) = 162.33(2)°). The perpendicular plane is formed by the amidic N(1) and the pyridinic N(2) nitrogen atoms of the pyridylamidate moiety, which acts with a N(1)−Ru−N(2) bite angle of 75.11(8)°, the hydride ligand disposed trans to N(2) (H(01)−Ru−N(2) = 169.4(10)°), and the carbonyl group located trans to N(1) (C(15)−Ru−N(1) = 176.50(10)°). The Ru−N(1) bond length of 2.117(2) Å compares well with the Ru−N distances reported for ruthenium amidate compounds26c,32 and is 0.13 Å shorter than the Ru−N(2) bond length of 2.247(2) Å. The lactamic N(1)−C(1) and C(1)−O(1) distances of 1.350(3) and 1.229(3) Å, respectively, are statistically identical with the related parameters of 1p. The 1H, 31P{1H}, and 13C{1H} NMR spectra of 1r,s, in benzene-d6, at room temperature are consistent with the structure shown in Figure 5. In agreement with the presence of a hydride ligand in these compounds, the 1H NMR spectra in the high-field region contain at −14.69 (1r) and −13.33 ppm (1s) triplets with H−P coupling constants of 21.3 and 24.0 Hz, respectively. As expected for inequivalent phosphine ligands, resulting from the bent nature of the tricycles, 31P{1H} NMR spectra show AB spin systems centered at 24.9 (1r) and 52.4 ppm (1s) and defined by Δν = 2341 Hz and JA‑B = 634 Hz and Δν = 2395 Hz and JA‑B = 676 Hz, respectively. In the 13C{1H} NMR spectra, the lactamic CO resonances appear at 174.6 (1r) and 175.6 ppm (1s), whereas the ν(CO) bands are observed at 1679 (1r) and 1670 cm−1 (1s) in the IR spectra, along with the ν(MCO) absorptions at 1866 (1r) and 1881 cm−1 (1s).
Scheme 10
coordinate bis(phosphine) d6 metal fragments at the 2-positon of the tricycle, which were isolated as brown solids in 67% and 78% yields, respectively. Their formation involves the heterolytic N−H bond activation of the lactam promoted by one of the hydride ligands of the unsaturated five-coordinate dihydride species MH2(CO)(PiPr3)2, which are generated as a consequence of the BH3 release from the starting complexes according to the previously mentioned general behavior of these types of compounds. As for 1p, the coordination of the pyridyl substituent of the four-membered ring stabilizes the resulting unsaturated monohydride intermediates. Ruthenatrinem 1s was characterized by an X-ray diffraction analysis. Figure 5 shows a view of the tricycle, which displays a bent angle between the five- and four membered rings of 37.92°. This angle is more closed than those of 1a,m,p by about 18, 16, and 7°, respectively. The comparison points out that the transition metal at the 2-position and its associated ligands exercise a marked influence on the bent angle of the tricycle. The coordination geometry around the ruthenium atom can be rationalized as derived from a distorted octahedron with the phosphorus atoms of the triisopropylphosphine ligands
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CONCLUDING REMARKS This paper shows the discovery of an unprecedented class of tribactams containing a transition metal and its associated ligands at the 2-position of the tricyclic skeleton and reveals that these metallatrinems can be formed through chelated assisted heterolytic N−H bond activation of 2-azetidinones substituted at the 4-position of the four-membered ring with an N-heterocycle, including pyridine, quinoline, isoquinoline, imidazole, and benzimidazole. The procedure is compatible with a wide range of transition-metal starting complexes (halfsandwich and diolefin dimers, polyhydride or tetrahydroborate derivatives) and external and internal bases, including the hydride ligand. This versatility allows polycycles to be built 1825
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Organometallics
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z): calcd for C17H15N2O [M + H]+ 263.1179, found 263.1160. IR (CH2Cl2, cm−1): ν (CN) 1618, 1582, 1503. 1H NMR (300 MHz, CDCl3, 298 K): δ 9.70−9.64 (m, 1H, isoqn), 9.07 (s, 1H, CHN), 8.67 (d, JH−H = 5.6, 1H, isoqn), 7.90−7.84 (m, 1H, isoqn), 7.75−7.68 (m, 3H, isoqn), 7.47−7.42 (m, 2H, PMP), 7.03−6.97 (m, 2H, PMP), 3.86 (s, 3H, CH3O). 13C{1H} NMR (75.5 MHz, CDCl3, 298 K): δ 160.1 (s, C isoquin), 159.0 (s, C PMP), 152.2 (s, CHN), 144.1 (s, C PMP), 142.1 (s, C isoqn), 136.9 (s, C isoqn), 130.2 (s, CH isoqn), 128.5 (s, CH isoqn), 127.2 (s, CH isoqn), 127.1 (s, CH isoqn), 127.0 (s, CH isoqn), 122.6 (s, CH PMP), 122.4 (s, CH isoqn), 114.4 (s, CH PMP), 55.4 (s, CH3O). Preparation of N-((1-Methyl-1H-benzo[d]imidazol-2-yl)methylene)prop-2-en-1-amine (4d). A solution of allylamine (1.73 g, 30.28 mmol) and 1-methyl-1H-benzo[d]imidazole-2-carbaldehyde39 (0.80 g, 6.05 mmol) in dichloromethane (12 mL) was stirred at room temperature for 15 h in the presence of 6.05 g of anhydrous Na2SO4. The mixture was then filtered and evaporated to yield a yellow solid (1.2 g, quantitative). HRMS (electrospray, m/z): calcd for C12H13NaN3 [M + Na]+ 222.1002, found 222.0985. IR (CH2Cl2, cm−1): ν(CN) 1649. 1H NMR (300 MHz, CDCl3, 298 K): δ 8.55 (s, 1H, CHN), 7.85−7.82 (m, 1H, bzim), 7.45−7.28 (m, 3H, bzim), 6.17−6.02 (m, 1H, CH), 5.33−5.18 (m, 2H, CH2), 4.36−4.33 (m, 2H, CH2N), 4.19 (s, 3H, CH3N). 13C{1H} NMR (75.5 MHz, CDCl3, 298 K): δ 155.3 (s, CHN), 147.5 (s, C bzim), 142.6 (s, C bzim), 137.0 (s, C bzim), 135.1 (s, CH), 124.4 (s, CH bzim), 122.7 (s, CH bzim), 120.6 (s, CH bzim), 116.5 (s, CH2), 109.9 (s, CH bzim), 64.0 (s, CH2N), 31.9 (s, CH3N). Preparation of N-((1-Methyl-1H-imidazol-2-yl)methylene)prop-2-en-1-amine (4e). This compound was prepared as described for 4d starting from allylamine (3.20 g, 56.7 mmol), 1-methyl-1Himidazole-2-carbaldehyde (1.25 g, 11.35 mmol), and 11.35 g of anhydrous Na2SO4 in dichloromethane (25 mL). Yield (white solid): 1.69 g (quantitative). HRMS (electrospray, m/z): calcd for C8H12N3 [M + H]+ 150.1026, found 150.0999. IR (CH2Cl2, cm−1): ν(CN) 1650. 1H NMR (300 MHz, CDCl3, 298 K): δ 8.33 (s, 1H, CHN), 7.12 (s, 1H, imid), 6.94 (s, 1H, imid), 6.12−5.97 (m, 1H, CH), 5.26−5.12 (m, 2H, CH2), 4.25−4.20 (m, 2H, CH2N), 4.01 (s, 3H, CH3N). 13C{1H} NMR (75.5 MHz, CDCl3, 298 K): δ 153.6 (s, CH N), 142.8 (s, C im), 135.4 (s, CH), 128.8 (s, CH im), 124.5 (s, CH im), 115.5 (s, CH2), 63.3 (s, CH2N), 35.0 (s, CH3N). Preparation of (±)-cis-1-(4-Methoxyphenyl)-3-phenoxy-4(pyridin-2-yl)azetidin-2-one (3a). A solution of phenoxyacetyl chloride (3.32 g, 19.48 mmol) in anhydrous dichloromethane (5 mL) was purged with argon and cooled to −78 °C. A solution of triethylamine (3.03 g, 29.94 mmol) in dichloromethane (2.5 mL) was added dropwise. The mixture was stirred for 30 min at −78 °C, and a solution of 4-methoxy-N-(pyridin-2-ylmethylene)aniline (4a; 3.18 g, 14.98 mmol) in dichloromethane (2.5 mL) was slowly added by dropping. Upon completion of the addition, the cooling bath was removed; the reaction mixture was stirred at room temperature for 16 h and quenched with 2 mL of MeOH. The crude mixture was diluted with 15 mL of CH2Cl2 and washed with NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent evaporated. SiO2 chromatography (Hex/EtOAc 4/6) yielded analytically pure 3a (3.84 g, 74%) as a single cis isomer. HRMS (electrospray, m/z): calcd for C21H18NaN2O3 [M + Na]+ 369.1210, found 369.1174. IR (CHCl3, cm−1): ν(CO) 1756. 1H NMR (300 MHz, CDCl3, 298 K): δ 8.54−8.50 (m, 1H, py), 7.60 (td, JH−H = 7.7, 1.8, 1H, py), 7.42 (d, JH−H = 7.9, 1H, py), 7.34−7.29 (m, 2H, PMP), 7.21−7.13 (m, 3H, py + Ph), 6.94−6.87 (m, 1H, Ph), 6.86−6.79 (m, 4H, PMP + Ph), 5.61 (d, JH−H = 4.9, 1H, −CH), 5.55 (d, JH−H = 4.9, 1H, −CH), 3.74 (s, 3H, CH3O). 13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 162.2 (CO), 156.9 (s, C PMP), 156.6 (s, C Ph), 153.6 (s, C py), 149.3 (s, CH py), 136.3 (s, CH py), 130.3 (s, C PMP), 129.2 (s, CH Ph), 123.3 (s, CH py), 122.6 (s, CH py), 122.2 (s, CH Ph), 118.7 (s, CH PMP), 115.8 (s, CH Ph), 114.5 (s, CH PMP), 81.5 (s, −CH), 63.4 (s, −CH), 55.4 (CH3O). Preparation of (±)-cis-1-(4-Methoxyphenyl)-3-phenoxy-4(quinolin-2-yl)azetidin-2-one (3b). This compound was prepared as described for 3a starting from phenoxyacetyl chloride (1.36 g, 7.97
containing a variety of saturated and unsaturated metal fragments and four-, six-, and even seven-coordinated metal ions (d4, d6, d8). Furthermore, once the metallatrinem has been formed, the coordination sphere and oxidation state of the metal center can be modified, without affecting the sensitive 2azetidinone backbone, through reactions of substitution and oxidative addition, respectively. The metal fragment certainly has a significant influence on relevant parameters of the tribactam such as the IR stretching frequency of the lactamic carbonyl, which ranges from 1670 to 1710 cm−1, the bent angle between the five- and four-membered rings of the tricycle, which changes from 55.55 to 37.92° for the studied cases, and the N−CO bond length in the lactamic ring, which undergoes a notable shortening by replacement of Ir(η5-C5Me5)Cl by Ir(CO)2, OsH3(PiPr3)2, or RuH(CO)(PiPr3)2. It is clear that hard work now needs to be done in order to fully understand the influence of the metal fragment on the relevant parameters of this novel family of tribactams, in particular those determining their activity as inhibitors or antibiotics,33 because the potentiality of their components is impressive given the versatility of metal complexes that can be used to introduce the metal fragment into the polycycle and the possibility of modifying the coordination sphere of the metal through simple reactions.
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EXPERIMENTAL SECTION
General Information. All reactions involving the use of metallic complexes were carried out with rigorous exclusion of air using Schlenk-tube techniques. Solvents were obtained free of oxygen and water from a solvent purification apparatus. Et3N was distilled over CaH2 and stored under argon prior to use. Acid chlorides were distilled under argon prior to use. 1H, 13C{1H}, and 31P{1H} NMR spectra were recorded on 300, 400, and 500 MHz spectrometers. Chemical shifts (expressed in parts per million) are referenced to residual solvent peaks (1H, 13C{1H}) or external 85% H3PO4 (31P{1H}). Coupling constants J and N are given in hertz. Attenuated total reflection infrared spectra (ATR-IR) of solid samples were run on a FT-IR spectrometer. C, H, and N analyses were carried out with a CHNS/O analyzer. High-resolution electrospray mass spectra were acquired using a hybrid quadrupole time-of-flight spectrometer. 4Methoxy-N-(pyridin-2-ylmethylene)aniline (4a),34 [M(η5-C5Me5)Cl2]2 (M = Ir, Rh),35 [M(μ-OMe)(η4-COD)]2 (M = Ir, Rh),36 OsH6(PiPr3)2,37 and MH(η2-H2BH2)(CO)(PiPr3)2 (M = Os, Ru)31a were prepared by published methods. Preparation of 4-Methoxy-N-(quinolin-2-ylmethylene)aniline (4b). A solution of 1.55 g (9.84 mmol) of quinoline-2carbaldehyde and 0.88 g (7.13 mmol) of 4-methoxyaniline in 20 mL of EtOH was stirred at room temperature for 10 h. The formed solid was filtered and redissolved in Et2O (40 mL). Filtration and evaporation of the solvent yielded pure 4b (1.49 g, 5.70 mmol, 80%) as an orange solid. HRMS (electrospray, m/z): calcd for C17H15N2O [M + H]+ 263.1179, found 263.1129. IR (CH2Cl2, cm−1): ν (CN) 1622, 1599, 1591. 1H NMR (300 MHz, CDCl3, 298 K): δ 8.75 (s, 1H, CHN), 8.25 (d, JH−H = 8.6, 1H, quin), 8.10 (d, JH−H = 8.5, 1H, quin), 8.03 (d, JH−H = 8.6, 1H, quin), 7.69−7.53 (m, 2H, quin), 7.46−7.39 (m, 1H, quin), 7.36−7.31 (m, 2H, PMP), 6.89−6.83 (m, 2H, PMP), 3.68 (s, 3H, CH3O). 13C{1H} NMR (75.5 MHz, CDCl3, 298 K): δ 158.7 (s, C, PMP), 157.7 (s, C quin), 154.7 (s, CHN), 147.5 (s, C quin), 143.0 (s, C PMP), 136.0 (s, C qn), 129.4 (s, CH qn), 129.1 (s, CH qn), 128.3 (s, CH qn), 127.3 (s, CH qn), 127.0 (s, CH qn), 122.5 (s, CH PMP), 118.1 (s, CH qn), 114.1 (s, CH PMP), 55.0 (s, CH3O). Preparation of (E)-N-(Isoquinolin-1-ylmethylene)-4-methoxyaniline (4c). A solution of 0.58 g (3.70 mmol) of isoquinoline-1carbaldehyde38 and 0.46 g (3.70 mmol) of 4-methoxyaniline in 8 mL of EtOH was stirred at room temperature for 10 h. The formed solid was filtered, washed with cold EtOH (2 × 2 mL), and dried to give pure 4c (0.97 g, quantitative) as a red solid. HRMS (electrospray, m/ 1826
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Organometallics
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(CHCl3, cm−1): ν(CO) 1763. 1H NMR (300 MHz, CDCl3, 298 K): δ 7.29−7.18 (m, 2H, Ph), 7.09 (s, 1H, im), 7.00−6.93 (m, 1H, Ph), 6.92−6.80 (m, 3H, Ph + im), 5.76−5.61 (m, 1H, CH), 5.56 (bs, 1H, −CH), 5.18− 5.05 (m, 2H, CH2), 4.65 (bs, 1H, −CH), 4.24−4.13 (m, 1H, CH2N), 4.59−4.50 (m, 1H, CH2N), 3.56 (s, 3H, CH3N). 13 C{1H} NMR (75 MHz, CDCl3, 298 K): δ 164.7 (s, CO), 156.9 (s, C Ph), 141.8 (s, C im), 131.3 (s, CH), 129.6 (s, CH Ph), 128.7 (s, CH im), 122.2 (s, CH im), 122.1 (s, CH Ph), 118.8 (s, CH2), 115.1 (s, CH Ph), 84.9 (s, −CH), 53.9 (s, −CH), 43.2 (s, CH2N), 32.6 (s, CH3N). Isomerization of 3d into (±)-cis-4-(1-Methyl-1H-benzo[d]imidazol-2-yl)-3-phenoxy-1-(prop-1-enyl)azetidin-2-one (5a). To a sunlight -protected solution of 3d (0.55 g, 1.65 mmol) in anhydrous toluene (6 mL) was added RuCl2(CHPh)(PCy3)2 (67.9 mg, 0.082 mmol) in portions, under argon. The mixture was refluxed and monitored by thin-layer chromatography (TLC). After completion, the solvent was eliminated and the crude product was purified by SiO2 chromatography (Hex/EtOAc 7/3) to obtain analytically pure 5a as 1.6/1 E/Z mixture. Yield (yellow solid): 0.34 g (62%). IR (CHCl3, cm−1): ν(CO) 1758. 1H NMR (300 MHz, CDCl3, 298 K): δ 7.79−7.74 (m, 2H, bzim, E+Z), 7.40−7.26 (m, 6H, bzim, E+Z), 7.22−7.14 (m, 4H, Ph, E+Z), 6.98−6.86 (m, 6H, Ph, E +Z), 6.64 (dd, JH−H = 14.3, 1.7, 1H, =CHN, E), 6.33 (dd, JH−H = 9.3, 1.8, 1H, CHN, Z), 5.87 (d, JH−H = 5.0, 1H, −CH, Z), 5.71 (d, JH−H = 5.0, 1H, −CH, Z), 5.66 (s, 2H, 2 x −CH, E), 5.17−4.98 (m, 2H, CHCH3, E+Z), 3.88 (d, JH−H = 1.6, 6H, CH3N, E+Z), 1.61 (dd, JH−H = 7.0, 1.7, 6H, CH3CH, E+Z). 13C{1H} NMR (75 MHz, CDCl3, 298 K, E+Z): δ 163.1 (s, CO, E), 161.4 (s, CO, Z), 156.8 (s, C Ph, E), 156.8 (s, C Ph, Z), 147.1 (s, C bzim, Z), 146.4 (s, C bzim, E), 142.2 (s, C bzim, E+Z), 137.0 (s, C bzim, E), 136.9 (s, C bzim, Z), 129.6 (s, C Ph, E), 129.5 (s, CH Ph, Z), 123.3 (s, CH Ph, Z), 123.2 (s, CHN, Z), 122.9 (s, CHN, E), 122.3 (s, CH Ph, E), 120.8 (s, CH bzim, E), 120.0 (s, CH bzim, Z), 119.9 (s, CH bzim, E), 119.5 (s, CH bzim, Z), 116.0 (s, CH Ph, Z), 115.9 (s, CH Ph, E), 113.5 (s, CHCH3, Z), 111.8 (s, CHCH3, E), 109.4 (s, CH bzim, Z), 109.3 (s, CH bzim, E), 83.6 (s, −CH, Z), 83.0 (s, −CH, E), 60.2 (s, −CH, E), 58.1 (s, −CH, Z), 30.8 (s, CH3N, E+Z), 14.9 (s, CH3CH, E), 12.8 (s, CH3CH, Z). Isomerization of trans-3e into (±)-trans-4-(1-Methyl-1Himidazol-2-yl)-3-phenoxy-1-(prop-1-enyl)azetidin-2-one (5b). This compound was prepared as described for 5a starting from trans-3e (1.10 g, 3.88 mmol) and RuCl2(CHPh)(PCy3)2 (159.6 mg, 0.194 mmol). Pure 5b was obtained as a 1/6 E/Z mixture after purification by SiO2 chromatography (Hex/EtOAc 4/6). Yield (yellow oil): 0.70 g (64%). IR (CHCl3, cm−1): ν(CO) 1754. 1H NMR (300 MHz, CDCl3, 298 K): δ 7.31−7.23 (m, 4H, Ph, E+Z), 7.13 (d, JH−H = 1.2, 2H, im, E+Z), 7.05−6.98 (m, 2H, Ph, E+Z), 6.95−6.85 (m, 6H, Ph + im, E+Z), 6.48 (dd, JH−H = 14.3, 1.8, 1H, CHN, E), 6.02 (dd, JH−H = 9.0, 1.7, 1H, CHN, Z), 5.50 (d, JH−H = 1.8, 1H, −CH, Z), 5.45 (d, JH−H = 1.9, 1H, −CH, E), 5.18−5.08 (m, 1H, CHCH3, Z), 5.03 (d, JH−H = 1.9, 1H, −CH, Z), 5.01−4.91 (m, 1H, CHCH3, E), 4.90 (d, JH−H = 1.9, 1H, −CH, E), 3.68 (s, 3H, CH3N, E), 3.65 (s, 3H, CH3N, Z), 1.63−1.60 (m, 3H, CH3CH, E), 1.60 (dd, JH−H = 7.2, 1.7, 3H, CH3CH, Z). 13C{1H} NMR (75 MHz, CDCl3, 298 K, Z): δ 162.4 (s, CO), 157.0 (s, C Ph), 142.0 (s, C im), 129.7 (s, CH Ph), 129.0 (s, CHN), 122.5 (s, CH Ph), 122.4 (s, CH im), 120.1 (s, CH im), 116.8 (s, CHCH3), 115.3 (s, CH Ph), 85.5 (s, −CH), 57.3 (s, −CH), 32.8 (CH3N), 12.8 (CH3CH). Preparation of (±)-cis-3-Phenoxy-4-(pyridin-2-yl)azetidin-2one (2a). To an ice-cooled solution of 3a (1.00 g, 2.88 mmol) in CH3CN (90 mL) was slowly added a solution of cerium(IV) ammonium nitrate (CAN, 4.74 g, 8.66 mmol) in H2O (30 mL). The reaction mixture was kept at 0 °C, and progress was monitored by TLC until total consumption of the starting material. After completion, AcOEt, saturated aqueous NaHCO3, and saturated aqueous Na2SO3 were added to the reaction mixture and the two layers separated. The aqueous layer was extracted with AcOEt, and the combined organics were washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure, and the crude mixture was purified by SiO2 chromatography (Hex/EtOAc 4/6) to
mmol), 4b (1.40 g, 5.33 mmol), and Et3N (1.61 g, 15.91 mmol). 3b was obtained as a single cis isomer after purification by SiO2 chromatography (Hex/EtOAc 8/2). Yield (white solid): 1.48 g (70%). HRMS (electrospray, m/z): calcd for C25H21N2O3 [M + H]+ 397.1547, found 397.1501. IR (CHCl3, cm−1): ν(CO) 1755. 1H NMR (300 MHz, CDCl3, 298 K): δ 8.10 (t, JH−H = 8.9, 2H, qn), 7.80 (dd, JH−H = 8.1, 1.4, 1H, qn), 7.76−7.71 (m, 1H, qn), 7.62−7.52 (m, 2H, qn), 7.38−7.33 (m, 2H, PMP), 7.17−7.09 (m, 2H, Ph), 6.90−6.78 (m, 5H, Ph + PMP), 5.74 (d, JH−H = 5.0, 1H, −CH), 5.71 (d, JH−H = 5.0, 1H, −CH), 3.74 (s, 3H, CH3O). 13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 162.5 (s, CO), 157.0 (s, C PMP), 156.7 (s, C Ph), 154.6 (s, C qn), 147.7 (s, C qn), 136.6 (s, C qn), 130.4 (s, C PMP), 129.8 (s, CH qn), 129.2 (s, CH Ph), 129.0 (s, CH qn), 127.8 (s, CH qn), 127.7 (s, CH qn), 126.9 (s, CH qn), 122.4 (s, CH Ph), 119.7 (s, CH qn), 118.7 (s, CH PMP), 115.9 (s, CH Ph), 114.5 (s, CH PMP), 81.9 (s, −CH), 64.0 (s, −CH), 55.4 (s, CH3O). Preparation of (±)-cis-4-(Isoquinolin-1-yl)-1-(4-methoxyphenyl)-3-phenoxyazetidin-2-one (3c). This compound was prepared as described for 3a starting from phenoxyacetyl chloride (0.90 g, 5.28 mmol), 4c (0.92 g, 3.52 mmol), and Et3N (1.07 g, 10.56 mmol). 3c was obtained as a single cis isomer after purification by SiO2 chromatography (Hex/EtOAc 4/6). Yield (white solid): 0.76 g (54%). HRMS (electrospray, m/z): calcd for C25H21N2O3 [M + H]+ 397.1547, found 397.1508. IR (CHCl3, cm−1): ν(CO) 1746. 1H NMR (300 MHz, CDCl3, 298 K): δ 8.52 (d, JH−H = 5.7, 1H, isoqn), 8.16 (bd, JH−H = 7.9, 1H, isoqn), 7.86 (d, JH−H = 8.3, 1H, isoqn), 7.69 (t, JH−H = 7.6, 1H, isoqn), 7.63−7.55 (m, 2H, isoqn), 7.37−7.34 (m, 2H, PMP), 7.07 (t, JH−H = 8.0, 2H, Ph), 6.88−6.78 (m, 3H, Ph), 6.68 (d, JH−H = 8.1, 2H, PMP), 6.21 (d, JH−H = 5.2, 1H, −CH), 5.82 (d, JH−H = 5.2, 1H, −CH), 3.76 (s, 3H, CH3O). 13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 162.3 (s, CO), 157.2 (s, C PMP), 156.4 (s, C Ph), 151.8 (s, C isoqn), 142.1 (s, C isoqn), 136.2 (s, C isoqn), 131.1 (s, CH isoqn), 129.9 (s, C PMP), 129.1 (s, C Ph), 127.5 (s, CH isoqn), 127.4 (s, CH isoqn), 127.2 (s, CH isoqn), 123.8 (s, CH isoqn), 122.3 (s, CH Ph), 121.0 (s, CH isoqn), 118.9 (s, CH PMP), 116.2 (s, CH Ph), 114.3 (s, CH PMP), 82.2 (s, −CH), 55.4 (s, −CH), 53.4 (s, CH3O). Preparation of (±)-cis-1-Allyl-4-(1-methyl-1H-benzo[d]imidazol-2-yl)-3-phenoxyazetidin-2-one (3d). This compound was prepared as described for 3a starting from phenoxyacetyl chloride (1.03 g, 6.03 mmol), 4d (0.60 g, 3.01 mmol), and Et3N (1.22 g, 12.05 mmol). 3d was obtained as a single cis isomer after purification by SiO2 chromatography (Hex/EtOAc 4/6). Yield (orange solid): 0.59 g (59%). HRMS (electrospray, m/z): calcd for C20H20N3O2 [M + H]+ 334.1550, found 334.1524. IR (CHCl3, cm−1): ν(CO) 1762. 1H NMR (300 MHz, CDCl3, 298 K): δ 7.82−7.76 (m, 1H, bzim), 7.37− 7.26 (m, 3H, bzim), 7.21−7.14 (m, 2H, Ph), 6.94 (t, JH−H = 7.6, 1H, Ph), 6.91−6.86 (m, 2H, Ph), 5.86−5.71 (m, 1H, CH), 5.65 (d, JH−H = 4.8, 1H, −CH), 5.40 (d, JH−H = 4.8, 1H, −CH), 5.26−5.17 (m, 2H, CH2), 4.41−4.33 (m, 1H, CH2N), 3.95−3.87 (m, 1H, CH2N), 3.78 (s, 3H, CH3N). 13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 164.8 (s, CO), 156.8 (s, C Ph), 147.3 (s, C bzim), 142.3 (s, C bzim), 136.5 (s, C bzim), 130.1 (s, CH), 129.4 (s, CH Ph), 123.0, 122.6, 122.1 (all s, CH bzim), 120.0 (s, CH2), 119.9 (s, CH Ph), 115.8 (s, CH Ph), 109.1 (s, CH bzim), 82.8 (s, −CH), 55.9 (s, −CH), 43.8 (s, CH2N), 30.4 (s, CH3N). Preparation of (±)-trans-1-Allyl-4-(1-methyl-1H-imidazol-2yl)-3-phenoxyazetidin-2-one (trans-3e). A solution of phenoxyacetyl chloride (4.50 g, 26.80 mmol) in 5 mL of anhydrous toluene was added dropwise via syringe to a solution of 4e (2.00 g, 13.40 mmol) and Et3N (5.40 g, 53.60 mmol) in 2.5 mL of refluxing toluene under argon. The resulting mixture was refluxed for 10 h. The crude mixture was diluted with 15 mL of CH2Cl2 and washed with saturated NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent evaporated under vacuum. The crude mixture (1/4 cis-/trans-3e) was purified by SiO 2 chromatography (Hex/EtOAc 3/7) to yield analytically pure lactam trans-3e. Yield (yellow solid): 1.20 g (31%). A 1.50 g portion (39%) of the cis/trans mixture was also recovered. HRMS (electrospray, m/z): calcd for C16H18N3O2 [M + H]+ 284.1394, found 284.1364. IR 1827
dx.doi.org/10.1021/om500162m | Organometallics 2014, 33, 1820−1833
Organometallics
Article
yield analytically pure 2a. Yield (white solid): 0.41 g (60%). HRMS (electrospray, m/z): calcd for C14H13N2O2 [M + H]+ 241.0972, found 241.0976. IR (CHCl3, cm−1): ν(CO) 1761. 1H NMR (300 MHz, CDCl3, 298 K): δ 8.46 (bd, JH−H = 4.8, 1H, py), 7.69−7.63 (m, 1H, py), 7.51 (d, JH−H = 7.8, 1H, py), 7.20−7.10 (m, 3H, py + Ph), 6.90 (t, JH−H = 7.3, 1H, Ph), 6.79 (d, JH−H = 8.1, 2H, Ph), 6.42 (bs, 1H, NH), 5.54 (dd, JH−H = 4.8, 2.6, 1H, −CH), 5.22 (d, JH−H = 4.8, 1H, −CH). 13 C{1H} NMR (75 MHz, CDCl3, 298 K): δ 167.2 (s, CO), 157.0 (s, C Ph), 155.6 (s, C py), 149.1 (s, CH py), 136.6 (s, CH py), 129.4 (s, CH Ph), 123.4 (s, CH py), 122.5 (s, CH py), 122.4 (s, CH Ph), 115.9 (s, CH Ph), 83.7 (s, −CH), 59.8 (s, −CH). Preparation of (±)-cis-3-Phenoxy-4-(quinolin-2-yl)azetidin2-one (2b). This compound was prepared as described for 2a starting from 3b (0.70 g, 1.76 mmol) in CH3CN (60 mL) and CAN (2.90 g, 5.30 mmol) in H2O (18 mL). Pure 2b was obtained after purification by SiO2 chromatography (Hex/EtOAc 6/4) as a pale brown solid. Yield: 0.38 g (75%). HRMS (electrospray, m/z): calcd for C18H15N2O2 [M + H]+ 291.1128, found 291.1129. IR (CHCl3, cm−1): ν(CO) 1764. 1H NMR (300 MHz, CDCl3, 298 K): δ 8.18 (d, JH−H = 8.5, 1H, qn), 8.03 (d, JH−H = 8.5, 1H, qn), 7.82 (d, JH−H = 8.1, 1H, qn), 7.74−7.68 (m, 1H, qn), 7.65 (d, JH−H = 8.6, 1H, qn), 7.58−7.52 (m, 1H, qn), 7.17−7.10 (m, 2H, Ph), 6.92−6.82 (m, 3H, Ph), 6.75 (bs, 1H, NH), 5.66 (dd, JH−H = 4.8, 2.5, 1H, −CH), 5.40 (d, JH−H = 4.8, 1H, −CH). 13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 166.7 (s, CO), 157.0 (s, C Ph), 155.8 (s, C qn), 147.4 (s, C qn), 136.4 (s, C qn), 129.8 (s, CH qn), 129.3 (s, CH Ph), 129.0 (s, CH qn), 127.7 (s, CH qn), 126.8 (s, CH qn), 122.3 (s, CH Ph), 119.6 (s, CH qn), 115.8 (s, CH Ph), 83.9 (s, −CH), 60.0 (s, −CH). Preparation of (±)-cis-4-(Isoquinolin-1-yl)-3-phenoxyazetidin-2-one (2c). This compound was prepared as described for 2a starting from 3c (0.35 g, 0.88 mmol) in CH3CN (30 mL) and CAN (1.45 g, 2.65 mmol) in H2O (9 mL). Pure 2c was obtained after purification by SiO2 chromatography (Hex/EtOAc 6/4) as a slightly colored solid. Yield: 0.11 g (41%). HRMS (electrospray, m/z): calcd for C18H15N2O2 [M + H]+ 291.1128, found 291.1130. IR (CHCl3, cm−1): ν(CO) 1759. 1H NMR (300 MHz, DMSO-d6, 298 K): δ 9.05 (s, 1H, NH), 8.52 (d, JH−H = 5.6, 1H, isoqn), 8.20 (d, JH−H = 8.4, 1H, isoqn), 7.96 (d, JH−H = 8.1, 1H, isoqn), 7.78 (d, JH−H = 5.7, 1H, isoqn), 7.73 (dd, JH−H = 8.4, 6.7, 1H, isoqn), 7.59 (dd, JH−H = 8.4, 6.7, 1H, isoqn), 7.08 (dd, JH−H = 8.6, 7.3, 2H, Ph), 6.85−6.80 (m, 1H, Ph), 6.63 (dd, JH−H = 7.6, 1.6, 2H, Ph), 5.96 (dd, JH−H = 5.0, 1.4, 1H, −CH), 5.92 (d, JH−H = 5.0, 1H, −CH). 13C{1H} NMR (75 MHz, DMSO-d6, 298 K): δ 166.0 (s, CO), 157.1 (s, C Ph), 155.2 (s, C isoqn), 141.4 (s, C isoqn), 135.2 (s, C isoqn), 130.1 (s, CH isoqn), 129.2 (s, CH Ph), 127.2, 127.0, 126.3, 124.5 (all s, CH isoqn), 121.8 (s, CH Ph), 120.4 (s, CH isoqn), 115.7 (s, CH Ph), 83.5 (s, −CH), 55.3 (s, −CH). Preparation of (±)-cis-4-(1-Methyl-1H-benzo[d]imidazol-2yl)-3-phenoxyazetidin-2-one (2d). Aqueous RuCl3 (0.30 g, 0.90 mmol) and solid NaIO4 (0.38 g, 1.80 mmol) were sequentially added to a solution of 5a (0.30 g, 0.90 mmol) in a 1,2-dichloroethane/water mixture (8 mL, 1/1). The reaction mixture was stirred at room temperature until completion (TLC). The mixture was quenched with aqueous Na2S2O3 and extracted with EtOAc. The organic phase was concentrated, and the resulting residue was dissolved in acetone and stirred with saturated aqueous NaHCO3 (0.33 mL) and Na2CO3 (0.02 mmol). The mixture was extracted with EtOAc, and the extract was washed with water, dried over MgSO4, filtered, and concentrated. The crude mixture was purified by SiO2 chromatography (EtOAc) to yield analytically pure 2d as a pale brown solid. Yield: 30 mg (13%). HRMS (electrospray, m/z): calcd for C17H16N3O2 [M + H]+ 294.1237, found 294.1238. IR (CHCl3, cm−1): ν(CO) 1772 cm−1. 1H NMR (300 MHz, CDCl3, 298 K): δ 7.80 (d, JH−H = 7.3, 1H, bzim), 7.44 (bs, 1H, NH), 7.38−7.27 (m, 3H, bzim), 7.22 (dd, JH−H = 8.6, 7.3, 2H, Ph), 7.00 (d, JH−H = 7.4, 1H, Ph), 6.94 (d, JH−H = 7.7, 2H, Ph), 5.71 (bd, JH−H = 4.7, 1H, −CH), 5.40 (d, JH−H = 4.7, 1H, −CH), 3.77 (s, 3H, CH3N). 13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 165.6 (s, CO), 157.0 (s, C Ph), 148.9 (s, C bzim), 142.1 (s, C bzim), 136.7 (s, C bzim), 129.6 (s, CH Ph), 123.2 (s, CH bzim), 122.9 (s, CH bzim),
122.4 (s, CH Ph), 119.9 (s, CH bzim), 116.1 (s, CH Ph), 109.2 (s, CH bzim), 84.2 (s, −CH), 52.5 (s, −CH), 30.4 (s, CH3N). Preparation of (±)-trans-4-(1-Methyl-1H-imidazol-2-yl)-3phenoxyazetidin-2-one (2e). This compound was prepared as described for 2d starting from 5b (0.66 g, 2.33 mmol), RuCl3 (17 mg, 0.08 mmol), NaIO4 (0.97 g, 4.66 mmol) in 1,2-DCE (11 mL), and H2O (11 mL). Pure 2e was obtained after purification by SiO2 chromatography (EtOAc) as a reddish solid. Yield: 90 mg (16%). HRMS (electrospray, m/z): calcd for C13H14N3O2 [M + H]+ 244.1081, found 244.1083. IR (CHCl3, cm−1): ν(CO) 1769. 1H NMR (300 MHz, CDCl3, 298 K): δ 7.55 (bs, 1H, NH), 7.31−7.25 (m, 2H, Ph), 7.07−6.97 (m, 4H, Ph + imid), 6.91 (bs, 1H, im), 5.47 (bs, 1H, −CH), 4.82 (d, JH−H = 1.8, 1H, −CH), 3.62 (s, 3H, CH3N). 13 C{1H} NMR (75 MHz, CDCl3, 298 K): δ 165.6 (s, CO), 157.1 (s, C Ph), 143.7 (s, C im), 129.7 (s, C Ph), 128.1 (s, CH im), 122.5 (s, CH im), 122.4 (s, CH Ph), 115.6 (s, CH Ph), 86.3 (s, −CH), 51.7 (s, −CH), 32.8 (s, CH3N). Reaction of [Ir(η5-C5Me5)Cl2]2 with 2a: Preparation of 1a. A mixture of [Ir(η5-C5Me5)Cl2]2 (33.4 mg, 0.042 mmol), 2a (20 mg, 0.084 mmol), and NaOAc (16.1 mg, 0.196 mmol) in dichloromethane (10 mL) was stirred overnight at room temperature. After this time, the crude mixture was filtered through Celite and evaporated to dryness. The obtained residue was dissolved in the minimum amount of dichloromethane, and diethyl ether was added to afford a yellow solid that was dried in vacuo. Yield: 46 mg (93%). This complex was isolated as a 5/1 diastereomeric mixture. The diastereomeric ratio was determined by integration of well-resolved signals in the 1H NMR spectra and indicated as [M] for the major and [m] for the minor. Separation of the diastereoisomers was not possible by SiO 2 chromatography or any other means. HRMS (electrospray, m/z): calcd for C24H26IrN2O2 [M − Cl]+ 567.1619, found 567.1632. IR (CHCl3, cm−1): ν(CO) 1696 (s). 1H NMR (300 MHz, CDCl3, 298 K): δ 8.88 (d, JH−H = 5.6, 1H, py, [m]), 8.59 (d, JH−H = 5.6, 1H, py [M]), 7.71 (td, J = 7.7, 1.6, 2H, py, [M+m]), 7.40−7.20 (m, 8H, py + Ph, [M+m]), 7.13−7.05 (m, 4H, Ph, [M+m]), 7.02−6.94 (m, 2H, Ph, [M+m]), 5.75 (d, JH−H = 4.5, 1H, −CH, [M]), 5.74 (d, JH−H = 4.4, 1H, −CH, [m]), 5.14 (d, JH−H = 4.5, 1H, −CH, [M]), 4.89 (d, JH−H = 4.4, 1H, −CH, [m]), 1.87 (s, 15H, Cp*, [M]), 1.82 (s, 15H, Cp*, [m]). 13 C{1H} NMR (75 MHz, CDCl3, 298 K, [M]): δ 175.8 (s, CO), 162.5 (s, C py), 158.0 (s, C Ph), 150.3 (s, CH py), 137.8 (s, CH py), 129.5 (s, CH Ph), 124.5 (s, CH py), 122.5 (s, CH Ph), 121.8 (s, CH py), 115.7 (s, CH Ph), 86.5 (s, −CH), 82.7 (s, C Cp*), 65.6 (s, −CH), 9.8 (s, CH3 Cp*). Reaction of [Rh(η5-C5Me5)Cl2]2 with 2a: Preparation of 1b. This complex was prepared as described for 1a starting from [Rh(η5C5Me5)Cl2]2 (25.9 mg, 0.042 mmol), 2a (20.0 mg, 0.083 mmol), and NaOAc (16.1 mg, 0.196 mmol) in dichloromethane (4 mL). Yield (brown solid): 38 mg (90%). This complex was isolated as a 5/1 diastereomeric mixture. HRMS (electrospray, m/z): calcd for C24H26N2O2Rh [M − Cl]+ 477.1044, found 477.1051. IR (CHCl3, cm−1): ν(CO) 1684 (s). 1H NMR (300 MHz, CDCl3, 298 K): δ 8.88 (d, JH−H = 5.6, 1H, py, [m]), 8.56 (d, JH−H = 5.6, 1H, py, [M]), 7.68 (td, JH−H = 7.7, 1.5, 2H, py, [M+m]), 7.38−7.14 (m, 8H, py + Ph, [M+m]), 7.11−7.05 (m, 4H, Ph, [M+m]), 6.96 (td, JH−H = 7.3, 1.2, 2H, Ph, [M+m]), 5.66 (d, JH−H = 4.5, 1H, −CH, [M]), 5.65 (d, JH−H = 4.5, 1H, −CH, [m]), 4.85 (d, JH−H = 4.5, 1H, −CH, [M]), 4.58 (d, JH−H = 4.5, 1H, −CH, [m]), 1.89 (s, 15H, Cp*, [M]), 1.83 (s, 15H, Cp*, [m]).13C{1H} NMR (75 MHz, CDCl3, 298 K, [M]): δ 177.1 (s, CO), 161.6 (s, C py), 158.1 (s, C Ph), 149.7 (s, CH py), 137.5 (s, CH py), 129.5 (s, CH Ph), 124.2 (s, CH py), 122.9 (s, CH Ph), 121.7 (s, CH py), 115.7 (s, CH Ph), 94.8 (d, JC−Rh = 8.3, C Cp*), 83.2 (s, −CH), 64.7 (s, −CH), 9.9 (s, CH3 Cp*). Reaction of [Ir(η5-C5Me5)Cl2]2 with 2b: Preparation of 1c. This complex was prepared as described for 1a starting from [Ir(η5C5Me5)Cl2]2 (27.1 mg, 0.034 mmol), 2b (20.0 mg, 0.069 mmol), and NaOAc (13.4 mg, 0.163 mmol) in dichloromethane (3 mL). Yield (yellow solid): 43.1 mg (96%). This complex was isolated as a 1/1 diastereomeric mixture. HRMS (electrospray, m/z): calcd for C28H28IrN2O2 [M − Cl]+ 617.1776, found 617.1787. IR (CHCl3, cm−1): ν(CO) 1697. 1H NMR (300 MHz, CDCl3, 298 K): δ 8.64 1828
dx.doi.org/10.1021/om500162m | Organometallics 2014, 33, 1820−1833
Organometallics
Article
−CH, [M]), 5.06 (d, JH−H = 4.5, 1H, −CH, [m]), 1.95 (s, 15H, Cp*, [M]), 1.90 (s, 15H, [m]). 13C{1H} NMR (126 MHz, CDCl3, 298 K, [M]): δ 177.3 (s, CO), 163.8 (s, C isoqn), 158.3 (s, C Ph), 141.8 (s, C isoqn), 135.9 (s, C isoqn), 132.0 (s, CH isoqn), 129.2 (s, CH Ph), 127.9, 127.7, 126.4, 126.0, 122.9 (all s, CH isoqn), 121.8 (s, CH Ph), 116.5 (s, CH Ph), 94.8 (d, JC−Rh = 8.3, C Cp*), 86.2 (s, −CH), 65.2 (s, −CH), 9.9 (s, CH3 Cp*). Reaction of [Ir(η5-C5Me5)Cl2]2 with 2d: Preparation of 1g. This complex was prepared as described for 1a starting from [Ir(η5C5Me5)Cl2]2 (28.5 mg, 0.036 mmol), 2d (21.0 mg, 0.071 mmol), and NaOAc (13.8 mg, 0.169 mmol) in dichloromethane (3 mL). Yield (yellow solid): 45.0 mg (96%). This complex was isolated as a single diastereomer. HRMS (electrospray, m/z): calcd for C27H29IrN3O2 [M − Cl]+ 620.1885 found 620.1896. IR (CHCl3, cm−1): ν(CO) 1703. 1 H NMR (300 MHz, CDCl3, 298 K): δ 7.65−7.60 (m, 1H, bzim), 7.46−7.36 (m, 3H, bzim), 7.32−7.25 (m, 2H, Ph), 7.18 (d, JH−H = 8.0, 2H, Ph), 7.03−6.96 (m, 1H, Ph), 5.82 (d, JH−H = 4.5, 1H, −CH), 5.04 (d, JH−H = 4.5, 1H, −CH), 3.87 (s, 3H, CH3N), 1.99 (s, 15H, Cp*). 13 C{1H} NMR (75 MHz, CDCl3, 298 K): δ 175.9 (s, CO), 159.7 (s, C bzim), 157.8 (s, C Ph), 138.4 (s, C bzim), 137.0 (s, C bzim), 129.5 (s, CH Ph), 123.8 (s, CH bzim), 123.3 (s, CH bzim), 122.0 (s, CH Ph), 117.4 (s, CH bzim), 115.9 (s, CH Ph), 110.9 (s, CH bzim), 86.2 (s, C Cp*), 83.1 (s, −CH), 56.5 (s, −CH), 32.0 (s, CH3N), 10.6 (s, CH3 Cp*). Reaction of [Rh(η5-C5Me5)Cl2]2 with 2d: Preparation of 1h. This complex was prepared as described for 1a starting from [Rh(η5C5Me5)Cl2]2 (20.0 mg, 0.032 mmol), 2d (19.0 mg, 0.065 mmol), and NaOAc (12.6 mg, 0.153 mmol) in dichloromethane (3 mL). Yield (orange solid): 34.5 mg (94%). This complex was isolated as a single diastereomer. HRMS (electrospray, m/z): calcd for C27H29N3O2Rh [M − Cl]+ 530.1309, found 530.1325. IR (CHCl3, cm−1): ν(CO) 1690. 1H NMR (300 MHz, CDCl3, 298 K): δ 7.73−7.68 (m, 1H, bzim), 7.44−7.35 (m, 4H, bzim + Ph), 7.31−7.25 (m, 1H, Ph), 7.18 (d, JH−H = 8.1, 2H, Ph), 7.01−6.95 (m, 1H, Ph), 5.73 (d, JH−H = 4.5, 1H, −CH), 4.73 (d, JH−H = 4.5, 1H, −CH), 3.78 (s, 3H, CH3N), 1.98 (s, 15H, Cp*). 13C{1H} NMR (CDCl3, 75 MHz, 298 K): δ 177.3 (s, CO), 157.9 (s, C bzim), 157.5 (s, C Ph), 139.1 (s, C bzim), 137.2 (s, C bzim), 129.5 (s, CH Ph), 123.4 (s, CH bzim), 123.0 (s, CH bzim), 121.9 (s, CH Ph), 117.2 (s, CH bzim), 115.9 (s, CH Ph), 110.7 (s, CH bzim), 94.5 (d, JC−Rh = 8.6, C Cp*), 83.9 (s, −CH), 56.0 (s, −CH), 31.6 (s, CH3N), 10.6 (s, CH3 Cp*). Reaction of [Ir(η5-C5Me5)Cl2]2 with 2e: Preparation of 1i. This complex was prepared as described for 1a starting from [Ir(η5C5Me5)Cl2]2 (37.0 mg, 0.047 mmol), 2e (23.0 mg, 0.094 mmol), and NaOAc (18.2 mg, 0.222 mmol) in dichloromethane (5 mL). Yield (yellow solid): 52.3 mg (92%). This complex was isolated as a single diastereomer. HRMS (electrospray, m/z): calcd for C23H27IrN3O2 [M − Cl]+ 570.1728, found 570.1734. IR (CHCl3, cm−1): ν(CO) 1695. 1 H NMR (300 MHz, CDCl3, 298 K): δ 7.31−7.20 (m, 4H, Ph + im), 7.03−6.92 (m, 3H, Ph + im), 4.92 (d, JH−H = 2.3, 1H, −CH), 4.73 (d, JH−H = 2.3, 1H, −CH), 3.54 (s, 3H, CH3N), 1.91 (s, 15H, Cp*). 13 C{1H} NMR (75 MHz, CDCl3, 298 K): δ 175.2 (s, CO), 157.8 (s, C Ph), 153.7 (s, C im), 129.5 (s, CH Ph), 124.4 (s, CH im), 122.9 (s, CH im), 122.2 (s, CH Ph), 117.1 (s, CH Ph), 85.5 (s, C Cp*), 84.9 (s, −CH), 57.4 (s, −CH), 34.3 (s, CH3N), 9.9 (s, CH3 Cp*). Reaction of [Rh(η5-C5Me5)Cl2]2 with 2e: Preparation of 1j. This complex was prepared as described for 1a starting from [Rh(η5C5Me5)Cl2]2 (28.0 mg, 0.045 mmol), 2e (22.0 mg, 0.090 mmol), and NaOAc (17.5 mg, 0.210 mmol) in dichloromethane (5 mL). Yield (orange solid): 41.7 mg (90%). This complex was isolated as a single diastereomer. HRMS (electrospray, m/z): calcd for C23H27N3O2Rh [M − Cl]+ 480.1153, found 480.1157. IR (CHCl3, cm−1): ν(CO) 1684. 1H NMR (300 MHz, CDCl3, 298 K): δ 7.26−7.16 (m, 4H, Ph + im), 7.00−6.90 (m, 3H, Ph + im), 4.93 (d, JH−H = 2.3, 1H, −CH), 4.39 (d, JH−H = 2.5, 1H, −CH), 3.41 (s, 15H, Cp*). 13C{1H} NMR (CDCl3, 75 MHz, 298 K): δ 177.4 (s, CO), 158.2 (s, C Ph), 151.9 (s, C im), 129.9 (s, CH Ph), 125.0 (s, CH im), 123.4 (s, CH im), 122.6 (s, CH Ph), 117.6 (s, CH Ph), 94.4 (d, JC−Rh = 8.5, C Cp*), 85.8 (s, −CH), 57.3 (s, −CH), 34.3 (s, CH3N), 10.3 (s, CH3 Cp*).
(d, JH−H = 8.7, 1H, qn), 8.39 (d, JH−H = 8.7, 1H, qn), 8.18 (d, JH−H = 8.4, 1H, qn), 8.11 (d, JH−H = 8.4, 1H, qn), 7.92−7.72 (m, 5H, qn), 7.67−7.51 (m, 3H, qn), 7.38−7.20 (m, 6H, Ph), 7.09−6.91 (m, 4H, Ph), 6.14 (d, JH−H = 4.3, 1H, −CH), 5.92 (d, JH−H = 4.5, 1H, −CH), 5.34 (d, JH−H = 4.5, 1H, −CH), 5.17 (d, JH−H = 4.3, 1H, −CH), 1.88 (s, 15H, Cp*), 1.70 (s, 15H, Cp*). 13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 176.6 (s, CO), 175.0 (s, CO), 163.8 (s, C qn), 163.8 (s, C qn), 158.3 (s, C Ph), 158.0 (s, C Ph), 146.3 (s, C qn), 145.7 (s, C qn), 138.2 (s, C qn), 138.0 (s, C qn), 132.3, 131.0, 130.1 (all s, CH qn), 129.6 (s, CH Ph), 129.3 (s, CH Ph), 129.1, 128.3, 128.2, 127.6, 127.4, 121.9, 121.6 (all s, CH qn), 119.1 (s, CH Ph), 118.7 (s, CH Ph), 115.9 (s, CH Ph), 87.3 (s, −CH), 86.3 (s, C Cp*), 86.3 (s, C Cp*), 83.2 (s, −CH), 68.6 (s, −CH), 67.9 (s, −CH), 10.5 (s, CH3 Cp*), 9.7 (s, CH3 Cp*). Reaction of [Rh(η5-C5Me5)Cl2]2 with 2b: Preparation of 1d. This complex was prepared as described for 1a starting from [Rh(η5C5Me5)Cl2]2 (26.6 mg, 0.043 mmol), 2b (25.0 mg, 86 mmol), and NaOAc (16.7 mg, 0.204 mmol) in dichloromethane (4 mL). Yield (orange solid): 39 mg (80%). This complex was isolated as a 1.3/1 diastereomeric mixture. HRMS (electrospray, m/z): calcd for C28H28N2O2Rh [M − Cl]+ 527.1200, found 527.1197. IR (CHCl3, cm−1): ν(CO) 1690. 1H NMR (300 MHz, CDCl3, 298 K, broad signals): δ 8.73 (s, 1H, qn, [m]), 8.43 (s, 1H, qn, [M]), 8.22−8.11 (m, 2H, qn, [M+m]), 7.98−7.76 (m, 5H, qn, [M+m]), 7.64−7.53 (m, 2H, qn, [M+m]), 7.45 (s, 1H, qn, [M]), 7.41−7.17 (m, 6H, Ph, [M+m]), 7.14−6.84 (m, 4H, Ph, [M+m]), 5.93 (s, 1H, −CH, [m]), 5.84 (s, 1H, −CH, [M]), 5.24 (s, 1H, −CH, [m]), 4.98 (s, 1H, −CH, [M]), 1.92 (s, 15H, Cp*, [M]), 1.71 (s, 15H, Cp*, [m]). 13C{1H} NMR (CDCl3, 126 MHz, 298 K, [M+m]): δ 179.0 (s, CO), 176.6 (s, CO), 164.9 (s, C qn), 163.6 (s, C qn), 158.7 (s, C Ph), 158.5 (s, C Ph), 147.1, 146.2, 138.2, 138.0 (all s, C qn), 131.4, 131.0, 130.1 (all s, CH qn), 129.9 (s, CH Ph), 129.7 (s, CH Ph), 129.6, 129.5, 128.8, 128.5, 127.7, 127.4, 122.2, 121.9 (all s, CH qn), 120.1, 119.7, 116.3 (all s, CH Ph), 95.9 (d, JC−Rh = 8.3, C Cp*), 94.7 (d, JC−Rh = 8.3, C Cp*), 84.8 (s, −CH), 84.3 (s, −CH), 68.5 (s, −CH), 67.2 (s, −CH), 11.1 (s, CH3 Cp*), 10.1 (s, CH3 Cp*). Reaction of [Ir(η5-C5Me5)Cl2]2 with 2c: Preparation of 1e. This complex was prepared as described for 1a starting from [Ir(η5C5Me5)Cl2]2 (26.1 mg, 0.032 mmol), 2c (19.0 mg, 0.065 mmol), and NaOAc (12.4 mg, 0.152 mmol) in dichloromethane (3 mL). Yield (yellow solid): 39.8 mg (94%). This complex was isolated as a 7/1 diastereomeric mixture. HRMS (electrospray, m/z): calcd for C28H28IrN2O2 [M − Cl]+ 617.1776, found 617.1772. IR (CHCl3, cm−1): ν(CO) 1699. 1H NMR (500 MHz, CDCl3, 298 K, [M + m (characteristic signals)]): δ 8.46 (d, JH−H = 6.4, 1H, isoqn, [M]), 8.01 (d, 1H, JH−H = 8.4, isoqn, [M]), 7.91 (d, JH−H = 8.3, 1H, isoqn, [M]), 7.83 (dd, JH−H = 8.1, 6.8, 1H, isoqn, [M]), 7.69 (d, JH−H = 6.4, 1H, isoqn, [M]), 7.65 (dd, JH−H = 8.3, 6.8, 1H, isoqn, [M]), 7.22 (dd, JH−H = 8.7, 7.2, 2H, Ph, [M]), 6.99−6.94 (m, 3H, Ph, [M]), 6.04 (d, JH−H = 4.6, 1H, −CH, [M]), 6.01 (d, JH−H = 4.7, 1H, −CH, [m]), 5.61 (d, JH−H = 4.6, 1H, −CH, [M]), 5.05 (d, JH−H = 4.7, 1H, −CH [m]), 1.95 (s, 15H, Cp*, [M]), 1.86 (s, 15H, Cp*, [m]). 13C{1H} NMR (126 MHz, CDCl3, 298 K, [M]): δ 176.2 (s, CO), 164.8 (s, C isoqn), 158.3 (s, C Ph), 142.5 (s, C isoqn), 136.0 (s, C isoqn), 132.2 (s, CH isoqn), 129.3 (s, CH Ph), 128.4, 128.0, 126.4, 125.8, 123.2 (all s, CH isoqn), 121.9 (s, CH Ph), 116.5 (s, CH Ph), 86.6 (s, C Cp*), 85.7 (s, −CH), 66.3 (s, −CH), 9.8 (s, CH3 Cp*). Reaction of [Rh(η5-C5Me5)Cl2]2 with 2c: Preparation of 1f. This complex was prepared as described for 1a starting from [Rh(η5C5Me5)Cl2]2 (19.8 mg, 0.032 mmol), 2c (19.0 mg, 0.065 mmol). and NaOAc (12.4 mg, 0.152 mmol) in dichloromethane (4 mL). Yield (orange solid): 33.6 mg (92%). This complex was isolated as a 9/1 diastereomeric mixture. HRMS (electrospray, m/z): calcd for C28H28N2O2Rh [M − Cl]+: 527.1200, found 527.1219. IR (CHCl3, cm−1): ν(CO) 1688. 1H NMR (500 MHz, CDCl3, 298 K, [M + m (characteristic signals)]): δ 8.42 (d, 1H, JH−H = 6.4, isoqn, [M]), 7.91−7.88 (m, 2H, isoqn, [M]), 7.80−7.75 (m, 2H, isoqn, [M]), 7.60 (dd, JH−H = 8.2, 6.8, 1H, isoqn, [M]), 7.20 (dd, JH−H = 8.7, 7.1, 2H, Ph, [M]), 6.97−6.92 (m, 3H, Ph, [M]), 5.92 (d, JH−H = 4.6, 1H, −CH, [M]), 5.90 (d, JH−H = 4.5, 1H, −CH, [m]), 5.30 (d, JH−H = 4.6, 1H, 1829
dx.doi.org/10.1021/om500162m | Organometallics 2014, 33, 1820−1833
Organometallics
Article
398.9847. IR (cm−1): ν(CO) 2073 (s), 2007 (s); ν(CO) 1705 (s). H NMR (300 MHz, CD2Cl2, 298 K): δ 8.61 (d, JH−H = 5.0, 1H, py), 7.90 (t, 1H, JH−H = 5.0, py), 7.39 (m, 2H, py), 7.29 (t, JH−H = 7.9, 2H, m-Ph), 7.06−6.98 (m, 3H, o-Ph + p-Ph), 5.72 (d, JH−H = 4.6, 1H, −CH), 5.10 (d, JH−H = 4.1, 1H, −CH). 13C{1H}-APT plus HSQC and HMBC NMR (75.4 MHz, CD2Cl2, 298 K): δ 186.8 (d, JC−Rh = 63.0, Rh-CO), 185.5 (d, JC−Rh = 74.0, Rh-CO), 174.6 (s, CO), 163.5 (s, C py), 158.2 (s, Cipso Ph), 153.1 (s, CH py), 139.6 (s, CH py), 129.9 (s, CH Ph), 124.0 (s, CH py), 123.1 (s, CH py), 122.0 (s, CH Ph), 115.6 (s, CH Ph), 84.0 (s, CH), 66.2 (s, CH). Reaction of 1m with CH3I: Preparation of 1o. A dark orange suspension of 1m (123.0 mg, 0.252 mmol) was treated with CH3I (4 mL), and the resulting suspension was stirred protected from the light for 5 h at room temperature. After this time, the resulting solution was evaporated to dryness and pentane was added to afford a white solid that was washed with pentane (3 × 2 mL) and dried in vacuo. Yield: 122.6 mg (79%). This complex was isolated as a 4/6 diastereomeric mixture.40 The diastereomeric ratio was determined by integration of well-resolved signals in the 1H NMR spectra and indicated as [M] for the major and [m] for the minor isomer. Anal. Calcd for C17H14IIrN2O4: C, 32.44; H, 2.24; N, 4.45. Found: C, 32.64; H, 2.65; N, 4.25. HRMS (electrospray, m/z): calcd for C17H14IIrN2O4 [M]+ 630.9701, found 630.9761. IR (cm−1): ν(CO) 2113 (s), 2060 (s); ν(CO) 1710 (s). 1H NMR (300 MHz, CD2Cl2, 298 K): δ 8.89 (d, JH−H = 5.3, 1H, py, [M]), 8.66 (d, JH−H = 5.3, 1H, py [m]), 8.08− 8.02 (m, 1H, py, [M]+[m]), 7.61−7.45 (m, 2H, py + Ph, [M]+[m]), 7.38−7.31 (m, 2H, Ph, [M]+[m]), 7.15−7.03 (m, 3H, py + Ph, [M]+[m]), 5.87 (d, JH−H = 4.4, 1H, −CH [M]), 5.85 (d, JH−H = 4.4, 1H, −CH, [m]), 5.46 (d, JH−H = 4.4, 1H, −CH, [m]), 5.37 (d, JH−H = 4.4, 1H, −CH, [M]), 1.51 (s, 3H, −CH3, [m]), 1.41 (s, 3H, −CH3, [M]). 13C{1H}-APT plus HSQC and HMBC NMR (75.47 MHz, CD2Cl2, 298 K, [M] + [m]): δ 174.4, 173.2 (both s, CO), 163.5, 163.4 (both s, Ir-CO), 161.1, 160.2 (both s, C py), 158.4, 158.3 (both s, Ir-CO), 158.0, 157.9 (both s, Cipso Ph), 153.8, 152.0 (both s, CH py), 141.0 (s, CH Py), 130.0 (s, CH Ph), 126.5 (s, CH py), 126.3 (s, CH py), 124.1 (s, CH py), 124.0 (s, CH py), 122.7 (s, CH Ph), 116.2 (s, CH Ph), 116.0 (s, CH Ph), 84.4, 83.2, 69.2, 66.5 (all s, CH), −10.2, −12.0 (both s, CH3). Reaction of OsH6(PiPr3)2 with 2a: Preparation of 1p. A colorless solution of OsH6(PiPr3)2 (100 mg, 0.193 mmol) in toluene (10 mL) was treated with 2a (46.5 mg, 0.193 mmol) and heated under reflux during 12 h. After this time, the resulting solution was evaporated to dryness and pentane was added to afford a white solid that was washed with pentane (3 × 2 mL) and dried in vacuo. Yield: 117 mg (82%). Anal. Calcd for C32H56N2O2OsP2: C, 51.04; H, 7.50; N, 3.72. Found: C, 51.64; H, 7.40; N, 3.46. HRMS (electrospray, m/ z): calcd for C32H55N2O2OsP2 [M − H]+ 753.3430, found 753.3350. IR (cm−1): ν(CO) 1684 (s). 1H NMR (400 MHz, C7D8, 298 K): δ 9.15 (d, JH−H = 6.6, 1H, CH py), 7.48 (d, 2H, JH−H = 7.5, CH Ph), 7.20 (m, 2H, CH py), 7.04 (m, 2H, CH Ph), 6.97 (t, JH−H = 7.6, 1H, CH Ph), 6.88 (t, JH−H = 6.6, 1H, CH py), 6.31 (t, JH−H = 6.6, 1H, CH py), 5.63 (d, JH−H = 4.3, 1H, −CH), 4.70 (d, JH−H = 2.4, 1H, −CH), 2.27 (m, 3H, PCH(CH3)2), 1.93 (m, 3H, PCH(CH3)2), 1.20 (dd, JH−H = 6.8, JH−P = 12.4, 9H, PCH(CH3)2), 1.20 (dd, JH−H = 6.8, JH−P = 12.4, 9H, PCH(CH3)2), 1.02 (dd, JH−H = 7.1, JH−P = 11.8, 9H, PCH(CH3)2), 0.94 (dd, JH−H = 7.1, JH−P = 11.6, 9H, PCH(CH3)2), −11.72 (br, 3H, OsH). 1H{31P} NMR (500 MHz, C7D8, 183 K, highfield region): −11.48 (AB spin system, Δν = 778, JA‑B = 77.5, 2H, OsH), −12.56 (br s, 1H, OsH). t1(min) (ms, OsH, 500 MHz, C7D8, 233 K); 123 ± 4 (−11.48 ppm); 138 ± 4 (−12.56 ppm). 31P{1H} NMR (162 MHz, C7D8, 298 K): δ 27.3 (AB spin system, Δν = 2873, JA‑B = 680). 13C{1H}-APT plus HSQC and HMBC NMR (100.4 MHz, C7D8, 298 K): δ 175.2 (s, CO), 161.5 (s, C py), 158.8 (s, Cipso Ph), 156.2 (s, CH py), 134.0 (s, CH py), 129.1 (s, CH Ph), 122.4 (s, CH py), 121.2 (s, CH Ph), 121.1 (s, CH py), 116.5 (s, CH Ph), 84.7 (s, CH), 68.4 (s, CH), 29.8 (dd, JC−P = 20.6, JC−P = 2.9, PCH(CH3)2), 26.5 (dd, JC−P = 21.3, JC−P = 2.2, PCH(CH3)2), 20.7, 20.4, 19.6, 19.5 (all s, PCH(CH3)2). Reaction of OsH6(PiPr3)2 with 2b: Preparation of 1q. A colorless solution of OsH6(PiPr3)2 (100 mg, 0.193 mmol) in toluene
Reaction of [Ir(μ-OMe)(η4-COD)]2 with 2a: preparation of 1k. A yellow suspension of [Ir(μ-OMe)(η4-COD)]2 (91.5 mg, 0.138 mmol) in pentane (10 mL) was treated with 2a (66.3 mg, 0.276 mmol), and the resulting suspension was stirred for 4 h at room temperature. After this time an orange suspension was formed. The orange solid was washed with pentane (2 × 3 mL) and dried in vacuo. Yield: 115 mg (77%). Anal. Calcd for C22H23IrN2O2: C, 48.96; H, 4.29; N, 5.19. Found: C, 48.63; H, 4.29; N, 5.14. HRMS (electrospray, m/z): calcd for C22H23IrN2O2 539.1344, found 539.1306. IR (cm−1): ν(CO) 1687 (s). 1H NMR (400 MHz, CD2Cl2, 298 K): δ 8.05 (d, JH−H = 5.6, 1H, py), 7.86 (m, 1H, py), 7.50 (d, JH−H = 8.0, 1H, py), 7.34−7.27 (m, 3H, py + m-Ph), 7.07 (d, JH−H = 8.8, 2H, o-Ph), 6.99 (t, JH−H = 7.8, 1H, p-Ph), 5.71 (d, JH−H = 4.6, 1H, −CH), 5.36 (m, 1H, CH COD), 4.95 (d, JH−H = 4.6, 1H, −CH), 4.55 (m, 1H, CH COD), 3.68 (m, 1H, CH COD), 3.61 (m, 1H, CH COD), 2.32− 1.54 (m, 8H, CH2 COD). 13C{1H}-APT plus HSQC and HMBC NMR (100.62 MHz, CD2Cl2, 298 K): δ 172.6 (s, CO), 166.0 (s, C py), 158.3 (s, Cipso Ph), 148.5 (s, CH py), 139.1 (s, CH py), 129.8 (s, Cmeta Ph), 123.9 (s, CH py), 122.6 (s, Cpara Ph), 122.2 (s, CH py), 115.9 (s, Cortho Ph), 84.1 (s, CH), 67.8 (s, CH COD), 66.9 (s, CH), 65.9, 63.6, 62.2 (all s, CH COD), 32.8, 32.3, 31.9, 30.1 (all s, −CH2− COD). Reaction of [Rh(μ-OMe)(η4-COD)]2 with 2a: Preparation of 1l. A pale yellow suspension of [Rh(μ-OMe)(η4-COD)]2 (100.0 mg, 0.149 mmol) in pentane (10 mL) was treated with 2a (72.0 mg, 0.299 mmol), and the resulting suspension was stirred for 6 h at room temperature. After this time a bright yellow suspension was formed. The bright yellow solid was washed with pentane (2 × 3 mL) and dried in vacuo. Yield: 93 mg (69%). Anal. Calcd for C22H23N2O2Rh: C, 58.67; H, 5.15; N, 6.22. Found: C, 59.04; H, 5.36; N, 5.97. HRMS (electrospray, m/z): calcd for C22H23N2NaO2Rh [M + Na]+ 473.0707, found 473.0747. IR (cm−1): ν(CO) 1680 (s). 1H NMR (300 MHz, CD2Cl2, 298 K): δ 7.73 (m, 2H, py), 7.28 (m, 4H, py + m-Ph), 7.06 (d, JH−H = 7.8, 2H, o-Ph), 6.98 (t, JH−H = 7.3, 1H, p-Ph), 5.65 (m, 1H, CH COD), 5.59 (d, JH−H = 4.6, 1H, −CH), 4.82 (d, JH−H = 4.6, 1H, −CH), 4.69 (m, 1H, CH COD), 4.03 (m, 1H, CH COD), 3.91 (m, 1H, CH COD), 2.17−1.75 (m, 8H, CH2 COD). 13C{1H}-APT plus HSQC and HMBC NMR (75.47 MHz, CD2Cl2, 298 K,): δ 174.5 (s, CO), 164.8 (s C py), 158.5 (s, Cipso Ph), 148.0 (s, CH py), 138.2 (s, CH py), 129.8 (s, Cmeta Ph), 123.5 (s, CH py), 123.0 (s, Cpara Ph), 122.1 (s, CH py), 116.1 (s, Cortho Ph), 83.7 (s, JC−Rh = 2.2, CH), 81.5 (d, JC−Rh = 12.5, CH COD), 79.9 (d, JC−Rh = 11.7, CH COD), 79.5 (d, JC−Rh = 13.2, CH COD) 79.2 (d, JC−Rh = 12.4, CH COD), 65.6 (s, CH), 31.1, 31.4, 31.2, 29.6 (all s, −CH2− COD). Reaction of 1k with CO: Preparation of 1m. Carbon monoxide was bubbled through an orange solution of 1k (200 mg, 0.372 mmol) in dichloromethane (10 mL) for 10 min. After this time, the resulting solution was evaporated to dryness and pentane was added to afford a dark orange solid that was washed with pentane (3 × 2 mL) and dried in vacuo. Yield: 163 mg (90%). Anal. Calcd for C16H11IrN2O4: C, 39.34; H, 2.27; N, 5.74. Found: C, 38.94; H, 2.55; N, 5.50. HRMS (electrospray, m/z): calcd for C16H11IrN2O4 [M]+ 511.0253, found 511.0241. IR (cm−1): ν(CO) 2061 (s), 1991 (s); ν(CO) 1706 (s). 1 H NMR (400 MHz, CD2Cl2, 298 K): δ 8.85 (d, JH−H = 5.7, 1H, py), 8.00 (m, 1H, py), 7.55 (d, JH−H = 7.8, 1H, py), 7.42 (m, 1H, py), 7.30 (m, 2H, m-Ph), 7.06−7.02 (m, 3H, o-Ph + p-Ph), 5.82 (d, JH−H = 4.8, 1H, −CH), 5.25 (d, JH−H = 4.8, 1H, −CH). 13C{1H}-APT plus HSQC and HMBC NMR (75.4 MHz, CD2Cl2, 298 K): δ 178.9 (s, Ir-CO), 173.8 (s, CO), 171.9 (s, Ir-CO), 163.4 (s, C py), 158.0 (s, Cipso Ph), 153.9 (s, CH py), 140.9 (s, CH py), 129.9 (s, CH Ph), 125.2 (s, CH py), 123.6 (s, CH py), 122.6 (s, CH Ph), 116.0 (s, CH Ph), 85.2 (s, CH), 66.9 (s, CH). Reaction of 1l with CO: Preparation of 1n. Carbon monoxide was bubbled through a brown solution of 1l (100 mg, 0.186 mmol) in dichloromethane (10 mL) for 2 h. After this time, the resulting solution was evaporated to dryness and pentane was added to afford an orange solid that was washed with pentane (3 × 2 mL) and dried in vacuo. Yield: 80 mg (90%). Anal. Calcd for C16H12N2O4Rh: C, 48.14; H, 3.03; N, 7.02. Found: C, 48.33; H, 2.96; N, 7.42. HRMS (electrospray, m/z): calcd for C16H12N2O4Rh [M]+ 398.9931, found
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dx.doi.org/10.1021/om500162m | Organometallics 2014, 33, 1820−1833
Organometallics
Article
−13.33 (t, JH−P = 24.0, 1H, RuH). 31P{1H} NMR (121 MHz, C6D6, 298 K): δ 52.4 (AB spin system, Δν = 2395, JA‑B = 676). 13C{1H}-APT plus HSQC and HMBC NMR (75.3 MHz, C6D6, 298 K): δ 207.0 (s, Ru−CO), 175.6 (s, CO), 161.4 (s, C py), 159.2 (s, Cipso Ph), 153.9 (s, CH py), 135.7 (s, CH py), 129.7 (s, CH Ph), 121.9 (s, CH py), 121.7 (s, CH Ph), 121.5 (s, CH py), 116.8 (s, CH Ph), 84.7 (s, CH), 66.1 (s, CH), 27.6 (dd, JC−P = 16.6, JC−P = 2.6, PCH(CH3)2), 26.6 (dd, JC−P = 15.7, JC−P = 2.6, PCH(CH3)2), 20.6, 20.4, 19.6, 19.5 (all s, PCH(CH3)2). Structural Analysis of Complexes 1a,m,p,s. X-ray data were collected for the complexes on Bruker Smart APEX CCD and Bruker AXS Smart 100 CCD diffractometers equipped with a normal-focus 2.4 kW sealed-tube source (Mo radiation, λ = 0.71073 Å) operating at 50 kV and 40 mA (1p), 30 mA (1p,s) or 25 mA (1a). Data were collected over the complete sphere. Each frame exposure time was 10 s (1a,p,s) or 20 s (1m) covering 0.3° in ω. Data were corrected for absorption by using a multiscan method applied with the SADABS program.41 The structures were solved by Patterson or direct methods and refined by full-matrix least squares on F2 with SHELXL97,42 including isotropic and subsequently anisotropic displacement parameters. The hydrogen atoms (except hydrides) were observed in the least-squares Fourier maps or calculated and refined freely or refined using a restricted riding model. Hydrides of 1p were observed in the last cycles of refinement but refined too close to metals; therefore, a restricted refinement model was used. 1m cocrystallizes with 0.5 molecule of hydroquinone. Crystal data for 1a: C24H26ClIrN2O2·0.5C6H6 Mw = 641.17, yellow, prismatic block (0.18 × 0.16 × 0.07 mm), triclinic, space group P1̅, a = 10.853(2) Å, b = 10.896(2) Å, c = 12.009(3)Å, α = 98.514(4)°, β = 108.068(3)°, γ: =105.722(4)°, V = 1257.1(5) Å3, Z = 2, Z′ = 1, Dcalcd = 1.694 g cm−3, F(000) = 630, T = 120(2) K, μ = 5.443 mm−1, 9523 measured reflections (2θ = 3−50°, ω scans 0.3°), 4298 unique reflections (Rint = 0.1015), minimum/maximum transmission factors 0.693/1.000, final agreement factors R1 = 0.0546 (2936 observed reflections, I > 2σ(I)) and wR2 = 0.1193, 4298/0/265 data/restraints/ parameters, GOF = 0.993, largest peak and hole 2.032 and −1.143 e/ Å3 . Crystal data for 1m: C16H11IrN2O4·0.5C6H6O2, Mw = 542.52, orange, irregular block (0.16 × 0.04 × 0.04 mm), monoclinic, space group C2/c, a = 24.6159(14)Å, b = 8.1783(5)Å, c = 17.4801(10)Å, β = 101.6990(10)°, V = 3445.9(3) Å3, Z = 8, Z′ = 1, Dcalcd = 2.091 g cm−3, F(000) = 2072, T = 100(2) K, μ = 7.784 mm−1, 20493 measured reflections (2θ = 3−58°, ω scans 0.3°), 4160 unique reflections (Rint = 0.0549), minimum/maximum transmission factors 0.598/0.842, final agreement factors R1 = 0.0332 (3530 observed reflections, I > 2σ(I)) and wR2 = 0.0526, 4160/0/247 data/restraints/parameters, GOF = 1.127, largest peak and hole 0.832 and −1.066 e/Å3. Crystal data for 1p: C32H56N2O2OsP2, Mw = 752.93, colorless, irregular block (0.29 × 0.06 × 0.02 mm), monoclinic, space group P21/c, a = 18.5861(8) Å, b = 12.3352(5) Å, c = 15.5389(7) Å, β = 108.2130(10)°, V = 3384.0(3) Å3, Z = 4, Z′ = 1, Dcalcd = 1.478 g cm−3, F(000) = 1536, T = 100(2) K, μ = 3.892 mm−1, 50203 measured reflections (2θ = 3−58°, ω scans 0.3°), 8255 unique reflections (Rint = 0.0330), minimum/maximum transmission factors 0.588/0.842, final agreement factors R1 = 0.0205 (7272 observed reflections, I > 2σ(I)) and wR2 = 0.0456, 8255/3/379 data/restraints/parameters, GOF = 1.052, largest peak and hole 1.102 and −0.476 e/Å3. Crystal data for 1s: C33H54N2O3P2Ru, Mw = 689.79, colorless, irregular block (0.26 × 0.11 × 0.10 mm), monoclinic, space group P21/n, a = 14.4769(7) Å, b = 10.6595(5) Å, c = 23.1385(12) Å, β = 101.2010(10)°, V = 3502.6(3) Å3, Z = 4, Z′ = 1, Dcalcd = 1.308 g cm−3, F(000) = 1456, T = 100(2) K, μ = 0.572 mm−1, 31601 measured reflections (2θ = 3−58°, ω scans 0.3°), 8342 unique reflections (Rint = 0.0481), minimum/maximum transmission factors 0.728/0.842, final agreement factors R1 = 0.0391 (6631 observed reflections, I > 2σ(I)) and wR2 = 0.0816, 8342/0/385 data/restraints/parameters, GOF = 1.056, largest peak and hole 0.628 and −0.677 e/Å3.
(10 mL) was treated with 2b (56.2 mg, 0.193 mmol) and heated under reflux for 12 h. After this time, the resulting solution was evaporated to dryness and pentane was added to afford a white solid that was washed with pentane (3 × 2 mL) and dried in vacuo. Yield: 110 mg (71%). Anal. Calcd for C36H57N2O2OsP2: C, 53.91 H, 7.16; N, 3.49. Found: C, 53.62; H, 6.99; N, 3.68 HRMS (electrospray, m/z): calcd for C36H58N2O2OsP2 [M − H]+ 803.3507, found 803.3545. IR (cm−1): ν(CO) 1681 (s). 1H NMR (300 MHz, C6D6, 298 K): δ 9.74 (d, JH−H = 8.4, 1H, CH py), 7.56−7.06 (m, 9H, CH Py + Ph), 6.87 (t, JH−H = 7.0, 1H, CH py), 5.83 (d, JH−H = 3.6, 1H, −CH), 4.93 (d, JH−H = 3.6, 1H, −CH), 2.19 (m, 3H, PCH(CH3)2), 1.85 (m, 3H, PCH(CH3)2), 1.17 (dd, JH−H = 7.0, JH−P = 12.4, 9H, PCH(CH3)2), 1.07 (dd, JH−H = 7.1, JH−P = 12.2, 9H, PCH(CH3)2), 0.97 (dd, JH−H = 7.5, JH−P = 12, 9H, PCH(CH3)2), 0.82 (dd, JH−H = 7.1, JH−P = 10.9, 9H, PCH(CH3)2), −11.70 (br, 3H, OsH). 1H{31P} NMR (300 MHz, C7D8, 183 K, high-field region): −11.04 (br s, 2H, OsH), −13.03 (br, 1H, OsH). t1(min) (ms, OsH, 300 MHz, C7D8, 233 K); 54 ± 4 (−11.01 ppm); 65 ± 4 (−12.97 ppm). 31P{1H} NMR (162 MHz, C6D6, 298 K): δ 27.3 (AB spin system, Δν = 1691, JA‑B = 670). 13 C{1H}-APT plus HSQC and HMBC (75 MHz, C6D6, 298 K): δ 175.8 (s, CO), 163.7 (s, C qn), 159.2 (s, Cipso Ph), 148.3 (s, C qn), 136.2 (s, CH qn), 135.6 (s, CH Ph), 129.7 (s, CH py), 129.1 (s, CH qn), 128.8 (s, C qn), 128.5 (s, CH qn), 126.7 (s, CH qn), 121.8 (s, CH qn), 119.9 (s, CH Ph), 116.9 (s, CH Ph), 86.3 (s, CH), 71.6 (s, CH), 29.8 (dd, JC−P = 20.4, JC−P = 3.1, PCH(CH3)2), 26.7 (dd, JC−P = 19.8, JC−P = 2.7, PCH(CH3)2), 21.3, 21.0, 20.1 (all s, PCH(CH3)2). Reaction of OsH(η2-H2BH2)(CO)(PiPr3)2 with 2a: Preparation of 1r. A colorless solution of OsH(η2-H2BH2)(CO)(PiPr3)2 (100 mg, 0.180 mmol) in toluene (10 mL) was treated with 2a (43.4 mg, 0.180 mmol) and heated under reflux for 12 h. After this time, the resulting solution was evaporated to dryness and pentane was added to afford a brown solid that was washed with pentane (3 × 2 mL) and dried in vacuo. Yield: 105 mg (67%). Anal. Calcd for C33H54N2O3OsP2: C, 50.88; H, 6.99; N, 3.60. Found: C, 50.82; H, 6.90; N, 3.55. HRMS (electrospray, m/z): calcd for C33H55N2O3OsP2 [M + H]+ 781.3480, found 781.3299. IR (cm−1): ν(CO) 1866 (s), ν(CO) 1679 (s). 1H NMR (300 MHz, C6D6, 298 K): δ 9.15 (d, JH−H = 5.4, 1H, CH py), 7.47 (d, 2H, JH−H = 7.8, CH Ph), 6.87 (m, 2H, CH py), 6.87 (m, 1H, CH Ph), 6.29 (td, JH−H = 6.1, JH−P = 1.8, 1H, CH py), 5.47 (d, JH−H = 4.3, 1H, −CH), 4.33 (s, 1H, −CH), 2.71 (m, 3H, PCH(CH3)2), 232 (m, 3H, PCH(CH3)2), 1.31 (dd, JH−H = 6.9, JH−P = 12.9, 9H, PCH(CH3)2), 1.30 (dd, JH−H = 6.9, JH−P = 12.6, 9H, PCH(CH3)2), 0.99 (dd, JH−H = 6.7, JH−P = 12.5, 9H, PCH(CH3)2), 0.97 (dd, JH−H = 6.3, JH−P = 12.8, 9H, PCH(CH3)2), −14.69 (t, JH−P = 21.3, 1H, OsH). 31 1 P{ H} NMR (121 MHz, C6D6, 298 K): δ 24.9 (AB spin system, Δν = 2341, JA‑B = 634). 13C{1H}-APT plus HSQC and HMBC NMR (100.4 MHz, C6D6, 298 K): δ 188.3 (t, JC−P = 9.8, Os−CO), 174.6 (s, CO), 161.2 (s, C py), 159.1 (s, Cipso Ph), 154.7 (s, CH py), 135.1 (s, CH py), 129.7 (s, CH Ph), 122.3 (s, CH py), 121.8 (s, CH Ph), 121.2 (s, CH py), 116.8 (s, CH Ph), 84.8 (s, CH), 67.9 (s, CH), 28.4 (dd, JC−P = 21.3, JC−P = 2.2, PCH(CH3)2), 27.4 (dd, JC−P = 21.3, JC−P = 2.2, PCH(CH3)2), 20.7, 20.4, 19.6, 19.5 (all s, PCH(CH3)2). Reaction of RuH(η2-H2BH2)(CO)(PiPr3)2 with 2a: Preparation of 1s. A colorless solution of RuH(η2-H2BH2)(CO)(PiPr3)2 (100 mg, 0.215 mmol) in toluene (10 mL) was treated with 2a (51.6 mg, 0.215 mmol) and heated under reflux for 3 h. After this time, the resulting solution was evaporated to dryness and pentane was added to afford a brown solid that was washed with pentane (3 × 2 mL) and dried in vacuo. Yield: 115 mg (78%). Anal. Calcd for C33H54N2O3P2Ru: C, 57.46; H, 7.89; N, 4.06. Found: C, 57.82; H, 7.57; N, 4.37. HRMS (electrospray, m/z): calcd for C33H55N2O3P2Ru [M + H]+ 691.2738, found 691.2735. IR (cm−1): ν(CO) 1881 (s), ν(CO) 1670 (s). 1H NMR (300 MHz, C6D6, 298 K): δ 9.09 (d, JH−H = 5.4, 1H, CH py), 7.60 (d, 2H, JH−H = 8.7, CH Ph), 7.28 (m, 1H, CH py), 7.01 (m, 2H, CH Ph), 6.96 (m, 2H, CH Ph), 6.54 (td, JH−H = 5.8, JH−P = 1.8, 1H, CH py), 5.57 (d, JH−H = 4.1, 1H, −CH), 4.53 (d, JH−H = 4.1, 1H, −CH), 2.76 (m, 3H, PCH(CH3)2), 2.29 (m, 3H, PCH(CH3)2), 1.43 (dd, JH−H = 6.0, JH−P = 12.0, 9H, PCH(CH3)2), 1.43 (dd, JH−H = 9.0, JH−P = 15.0, 9H, PCH(CH3)2), 1.13 (dd, JH−H = 6.0, JH−P = 7.2, 9H, PCH(CH3)2), 1.09 (dd, JH−H = 2.8, JH−P = 7.2, 9H, PCH(CH3)2), 1831
dx.doi.org/10.1021/om500162m | Organometallics 2014, 33, 1820−1833
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ASSOCIATED CONTENT
S Supporting Information *
Figures giving 1H and 13C{1H} NMR spectra of compounds 4b−e, 3a−e, 5a,b, 2a−e, and 1a−j and CIF files giving positional and displacement parameters, crystallographic data, and bond lengths and angles of compounds 1a,m,p,s. This material is available free of charge via the Internet at http:// pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Authors
*E-mail for M.A.E.:
[email protected]. *E-mail for M.A.S.:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS Financial support from the Spanish MINECO (Projects CTQ2011-23459, CTQ2010-20714-C02-01/BQU and Consolider Ingenio 2010 (CSD2007-00006)), the DGA (E35), the CAM (S2009/PPQ-1634-AVANCAT), and the European Social Fund (FSE) is acknowledged. Johnson Matthey Catalysts is acknowledged for the donation of RhCl3·3H2O and IrCl3· 3H2O.
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REFERENCES
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Organometallics
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dx.doi.org/10.1021/om500162m | Organometallics 2014, 33, 1820−1833
