The Synthesis and Structural Characterization of Polycyclic

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The Synthesis and Structural Characterization of Polycyclic Derivatives of Cobalt Bis(dicarbollide)(1−) Bohumír Grüner,*,† Václav Šícha,† Drahomír Hnyk,† Michael G.S. Londesborough,† and Ivana Císařová‡ Institute of Inorganic Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Hlavní 1001, CZ-250 68 Ř ež, Czech Republic Department of Inorganic Chemistry, Faculty of Natural Sciences, Charles University, Hlavova 2030, 128 42 Prague 2, Czech Republic

† ‡

S Supporting Information *

ABSTRACT: The cobalt bis(dicarbollide) anion [(1,2-C2B9H11)2-3,3′-Co]− (1−) is an increasingly important building block for the design of new biologically active compounds. Here we report the reactions of lithiated 1− with N-(ω-bromoalkyl)phthalimides Br-(CH2)n-N(CO)2NC6H4 (where n = 1 to 3) that give a number of new compounds substituted at dicarbollide carbon atom positions. For n = 2 and 3, substitution of the cobalt bis(dicarbollide) anion is accompanied by cyclocondensation of the organic moieties to give polycyclic ring structures attached to the cage. Predominant products correspond to oxazolo[2,3-a]isoindol-5(9bH)-1,2,3-dihydro-9b-yl)(1-cobalt(III) bis(1,2-dicarbollide)(1−) (2−) and 1-(2H-[1,3]-oxazino[2,3a]isoindol-6(10bH)-1,3,4-dihydro-10b-yl)-(1-cobalt(III) bis(1,2dicarbollide)(1−) (4−) ions with isoindolone functions containing either five- or six-membered lateral oxazine rings. Additionally, products (tetrahydro-2-benzo[4,5]furan-1(3H)-1-[3,3]-yl-)-1,1′-μ-cobalt(III) bis(1,2-dicarbollide)(1−) (3−) and (2-(azetidin-yl-carbonyl)benzoyl-)-1-cobalt(III) bis(1,2-dicarbollide)(1−) (5−) were isolated, which display unusual cyclic structures featuring a bicyclic benzofuranone ring attached in a bridging manner by a quarternary carbon to two skeletal carbon atoms and a ketobenzoic acid amide substituent with a side azetidine ring. However, in the case of n = 1, only the anticipated methylene amine derivative [(1NH2CH2-1,2-C2B9H11)(1′,2′-C2B9H11)2-3,3′-Co]− (6−) was isolated in low yield after cleavage of the phthalimide intermediate species. The molecular structures of all isolated cyclic products 2− to 5− were confirmed by single-crystal X-ray diffraction studies, and the structure of cobalt bis(dicarbollide)-1-CH2NH2 6− was delineated using density functional theory applied at BP86/AE1 level in combination with NMR spectroscopy. Thus, the synthetic method described herein presents a facile route to new cobalt bis(dicarbollide) derivatives substituted by polycyclic structural motifs with potential biological activity.

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INTRODUCTION Interest in the unique properties of the cobalt(III) bis(1,2dicarbollide)(1 − ) anion [(1,2-C 2 B 9 H 11 ) 2 -3,3′-Co(III)] − (1−)1−4 has recently engendered several emerging applications. A key development to the application of this chemistry was the discovery of the easy cleavage of the B(8) atom-bonded ring in [(8-O(CH2CH2)2O-1,2-C2B9H10)-3,3′-Co(III)]− (or other closely related compounds),5 enabling the incorporation of the cobalt bis(dicarbollide) cluster framework into larger functional molecules and materials.2,4,6 These functional molecules include efficient extraction agents for lanthanides and actinides,7 biologically active species2,8−11 and probes,12 dendrimeric structures and their precursors,6,13−15 additives to polymers and membranes, and selective electrodes,6,16−19 among others. The use of reagents based on cleavable cyclic ether moieties5 results in lengthy linear connections, typically containing a chain of six atoms, between the cobalt bis(dicarbollide) cluster and its organic functionality. Note that some alternative building blocks based on a cleavable diatomic bridge20 or B-ammonium derivatives1,2,21 are also available. © 2015 American Chemical Society

A current goal in the synthetic development of this chemistry is concordantly the tuning of the distance between the cobalt bis(dicarbollide) cluster and its functional group. This is particularly relevant to drug design and would be best accessible via direct carbon substitution, in a similar fashion as in the carborane series.2 In this context we have been searching for suitable synthetic pathways to alkylamino compounds based on the cobalt bis(dicarbollide) anion (see Figure 1) as building blocks applicable in the design of biologically active compounds, particularly those targeting the inhibition of HIV protease9,10 and carbonic anhydrase IX enzymes.11 Regarding the direct carbon substitution of carboranes, the ortho-, meta-, and para-carborane isomers contain weakly acidic cage CH groups (pKa = 23, 26, and 30, respectively)22 that can be easily deprotonated by using strong bases, typically BuLi, and reacted with a wide scope of reagents; for examples, see refs 2 and 22. However, in the case of the cobalt bis(dicarbollide)Received: October 6, 2014 Published: March 26, 2015 3148

DOI: 10.1021/ic502450t Inorg. Chem. 2015, 54, 3148−3158

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Inorganic Chemistry

DME solvent, equivalent molar quantities of both BuLi and N(ω-bromoalkyl)phthalimide reagent were used (see Experimental Section for details). Despite the associated risk connected with the possibility of different reaction pathways,35,45,49 these conditions were selected in preference to other alternatives, due to (a) the widespread use of this procedure for alkylamine synthesis,33 (b) the availability of appropriate starting chemicals, and (c) the documented applicability of this method in the case of carborane derivatives.2,45−47 However, this method did not result in the anticipated straightforward formation of simple alkyl amine derivatives (see Figure 1), but instead resulted in the generation of substituted cobalt bis(dicarbollide) species with unexpected ring structures. Thus, for reactions with Br-(CH2)n-N(CO)2NC6H4, where n = 2 and 3, substitution proceeded in high yields to give main products whose structures were determined by single-crystal X-ray crystallography and shown in Figures 2−5.

Figure 1. Aminoderivatives of the cobalt bis(dicarbollide) ion as the anticipated products shown along with their cage-numbering scheme.

(1−) anion, C-substituted functional derivatives have been mainly prepared via indirect methods starting from modified carboranes followed by their degradation and subsequent metal insertion,1,2 examples of which include Hawthorne’s wellknown pyrazole-bridged Venus flytrap systems.23 Although the first reports on the feasibility of the lithiation of C−H bonds24,25 were published a long time ago, only limited examples exist of C-substituted derivatives obtained by direct methods. However, a recently renewed interest in the lithiation of C−H bonds in Cs1 has led to a renaissance of this approach and, from it, the synthesis of C-phosphine26,27 and hydrosilylated28−30 derivatives. This was closely followed by the direct formation of C−C bonds in a series of alkylhydroxy31 and (alkyl)carboxy derivatives and the respective amides.32 The synthesis of amines via the reaction of N-(ωhalogenoalkyl)phthalimides with deprotonated organic molecules, followed by cleavage of the phtalimide protective group under a variety of conditions, is a highly exploited reaction pathway in organic chemistry.33 When using some strong nucleophiles, some examples of cyclization reactions have been reported.34−40 Thus, for example, lithiated phenylacetylene, phenyllithium or phenyl- and benzyl-magnesium halides react with N-(2-bromoethyl) phtalimides to give cyclic 9-b-phenyl or 9-b-benzyl-2,3-dihydrooxazolo[2,3-a]isoindol-5-(9-b-H)-ones or closely related compounds in good yields.34−40 Cyclic compounds from these families have now found wide applications as biologically active species.39,41−44 Numerous contributions to the literature also outline the successful application of this reaction pathway to lithiated carboranes for the direct syntheses of primary aminoalkyl carborane derivatives.2,6,45−48 Note that two papers described a formation of cyclic structures at 1-substituted ortho-carborane.45,49 However, as yet, no attempts have been made at similar exploitations of this method with lithiated cobalt bis(dicarbollide) species. Only a cleavage of B(8)-substituted dioxane derivative with potassium phtalimide has been described for this series.50 Herein, we describe results from the reactions of some N-(ω-bromoalkyl)phthalimides with lithiated cobalt bis(dicarbollide) in dimethoxy ethane (DME) at low temperatures.

Figure 2. Molecular structure of the ion 2− (ORTEP view, 30% probability level); the Me4N+ cation is omitted for clarity. Selected interatomic distances [Å] and angles [deg]: Co3−C1 2.129 (2), Co3− C1′ 2.064(2), C1−C2 1.631(3), C1′−C2′ 1.606(3), C1−B6 1.727 (3), B4−B8 1.822(4), C1−C3 1.582(3), C8−C9 1.393(3), C3−O14 1.416(2), C10−O15 1.216(3), C13−O14 1.448(2),C3−N11 1.465 (2), C10−N11 1.378 (3); C1−Co3−C2 45.79 (7), C3−C1−Co3 116.12(1), C1−C2−B7 114.93(2), C1−C2−B6 61.73(1), C3−C1− C2 119.61(2), C3−C1−B6 108.60 (15), O14−C3−C4 112.46(2), N11−C3−C4 102.56 (2), O14−C3−N11 104.10(2), C10−N11−C12 121.90(2), O15−C10−N11 124.7(2).

Specifically, reaction of lithiated Cs1 with N-(2-bromoethyl)phthalimide (see Scheme 1), gave the oxazolo[2,3-a]isoindol5(9-b-H)-one,2,3-dihydro-9-b-cobalt bis(1,2-dicarbollide) (1−) anion (2−) as the major product in high yield (64%) when isolated as the Me4N2 salt. Its structure (Figure 2) contains a tricyclic moiety composed of an aromatic phenyl ring conjoined to two five-member rings. In this case, the formation of a stable five-atom central ring seems to be a potent driving force for the observed cyclization. The second most abundant product species (18%, according to HPLC analysis of the reaction mixture), isolated as Me4N3 only in 6% yield, contains a different type of substituent that is bicyclic and attached to the dicarbollide cage by a quarternary carbon atom in a bridging manner (see Figure 3 and Scheme 1). The substituent now interconnects two carbon atoms located in the two ligand planes; the mutual positions of the other two carbons are in the

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RESULTS AND DISCUSSION Initial efforts to synthesize aminoalkyl derivatives of 1− centered around reactions of lithiated Cs1 with N-(ωbromoalkyl)phthalimides Br-(CH2)n-N(CO)2NC6H4 (n = 1, 2, and 3). In these reactions, conducted at low temperature in 3149


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Figure 3. Molecular structure of 3− ion (ORTEP view, 30% probability level); the Me4N+ cation is omitted for clarity. The salt crystallized with CH2Cl2 solvent molecules in void. Selected interatomic distances [Å] and angles [deg]: Co3−C1 1.978(3), Co3−C1′ 1.986 (3), Co3−C2 2.037(3), Co3−C2′ 2.027(3), C1−C2 1.625(4), C1′−C2′ 1.624(4), C1−B4 1.762(5), C2−B7 1.701(5), C1−C3 1.560(4), C1′−C3 1.563(4), C3−C10 1.516(4), C3−O1 1.445(3), C4−O1 1.377(4), C4−O2 1.206(4); C1−Co3−C1′ 75.06(1), C2′−Co3−C2 139.30(1), C1−Co3−B7′ 143.97(1), C3− C1−Co3 92.02(2), C3−C1′−Co3 91.65(2), C1−Co3−B4′ 103.32(1), C3−C1−C2 114.7(2), C3−C1′−C2′ 111.7(2), C10−C3−C1 117.8(2), C3−C1−B4 117.9(2), B7−Co3−B7′ 125.22(2), B8− Co3−B8′ 117.64(1), C3−C1′−B4′ 120.2(2), O1−C3−C1 107.2(2), O1−C3−C1′ 109.2(2).

Figure 5. Molecular structure of 5− ion (ORTEP view, 30% probability level); the cation is omitted for clarity. Selected interatomic distances [Å] and angles [deg]: Co3−C1 2.081(3), C1−C2 1.631(4), C1′−C2′ 1.608(5), C1−C3 1.525(4), C9−C10 1.504(4), C11−C12 1.544(6), O1−C3 1.214(3), N1−C10 1.319(4), N1−C11 1.475(5), O1−C3 1.214(3), O2−C10 1.239(3), C2′−Co3−C1 136.53(1), C1′− Co3−C2 101.24(1), B8−Co3−B8′ 91.84(2), C3−C1−Co3 111.44(2), C3−C1−C2 112.4(2), C4−C3−C1 124.0(2), C8−C9− C10 118.1(2), O1−C3−C1 117.3(2), N1−C10−C9 117.2(2), N1− C13−C12 88.5(3), C11−N1−C13 94.0(3),C10−N1−C13 126.8(3), C10−N1−C11 130.3(3).

arrangement of an anti isomer, as discussed previously for other substituents.24,28,31 Similar preferential cyclizations were observed for the reaction of N-(3-bromopropyl) phthalimide, although with some differences. Here the respective tricyclic 2H-[1,3]oxazino[2,3-a]isoindol-6(10-b-H)-1,3,4-dihydro-10-b-cobalt bis(1,2-dicarbollide) ion formed in a 28% isolatable yield as (Cs4). The tricyclic ring is of an isoindolone type, with a six-member side ring comprising both oxygen and nitrogen atoms (Scheme 2 and Figure 4). Furthermore, inspection of the reaction mixture by high-performance liquid chromatography (HPLC) revealed the presence of high quantities of a second product that formed in a ratio of approximately 3:4 with respect to Cs4. This second product, containing a four-member azetidine ring attached via an amidic bond to the carboxylic function of the 2-ketobenzoic acid group (Scheme 2 and Figure 5), was isolated as (Me4N5) in 31% yield. Similarly to all other isolated species, this compound is quite stable in solution or when stored for a long time (months) at ambient temperature in the solid state. The formation of the cyclic products (2− to 5−) can be attributed to the ability of the lithiated cobalt bis(dicarbollide) cage to peferentially attack the carbonyl function and not the terminal -CH2- group in the bromoalkane chain. As depicted in Schemes 1 and 2 (upper lines) the first step in the reaction mechanism consists of a nucleophilic addition of the lithiated cobalt bis(dicarbollide) cage carbon atom to the carbonyl moiety present in the phtalimide group, while leaving the -CH2Br group in the alkyl chain available for further involvement in the cyclization process. Only the later stages of the reaction correspond to a mechanism of nucleophilic substitution in which the nucleophilic alcoholate ion reacts at the terminal

Figure 4. Molecular structure of 4− ion (ORTEP view, 30% probability level); the Me3NH+ cation present in this structure is omitted for clarity. Selected interatomic distances [Å] and angles [deg]:Co3−C1 2.149(2), Co3−C2 2.069 (2), Co3−B8 2.098 (3), C1−C2 1.623(3), C1′−C2′ 1.610(3), B7−B8 1.800(4), B4−B8 1.825(4), C1−C3 1.582(3), C3−N1 1.469(3), C10−N1 1.354(3), C3−O1 1.416(3), C13−O1 1.442(3), C10−O2 1.238(3); C2′−Co3− C1 104.53(9), C3−C1−Co3 116.96(1), C3−C1−C2 120.10(2), C4− C3−C1 114.05(2), C3−C1−B6 108.50(2), C3−C1−B4 126.73(2), N1−C3−C1 111.42(2), O1−C3−C1 107.60(2), O1−C3−N1 107.60(2), C3−O1−C13 112.72(2), C10−N1−C3 113.05(2).

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Scheme 1. Proposed Mechanism for the Formation of Cyclic Products 2− and 3− by Low-Temperature Reaction of Bromoethyl Phtalimide with Lithiated Cs1a

a

The second assumed lithiation step originates from an equilibrium between the monolithiated and dilithiated form, which typically occur in solutions of carboranes2.

Scheme 2. Proposed Mechanism for the Formation of Cyclic Products 4− and 5− from the Low-Temperature Reaction of Bromopropyl Phtalimide with Lithiated Cs1

substituent present at the vicinal carbon position of the orthocarborane cage.49 Similarly, the formation of a different ring structure bridging both carbon atoms in carborane cage was ascribed to the presence of a substituent in the starting 1-t-Budi-Me-silyl-carborane.45 The mechanism, rationalizing the formation of isoindolone rings in 2− and 4−, would closely correspond to that observed previously for organic nucleophiles such as phenylithium35 or for lithiated 1-phenyl-1,2-carborane,49 albeit no substituent is present in the vicinal carbon

polarized -CH2-Br carbon in the chain and forms a lateral ring in the polycyclic moiety (see Schemes 1 and 2). Considering related reactions of lithiated parent icosahedral carboranes with the N-(ω-bromoalkyl)phthalimides, only two literature reports describe formation of cyclic products.45,49 A cyclocondensation of N-(2-bromoethyl)pthalimide and lithiated 1-phenyl-ocarborane results in an isoindolone structure,49 which parallels this observed in the metallacarborane 2−. The cyclization was explained in terms of an inductive effect of the phenyl 3151


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Inorganic Chemistry Scheme 3. Synthesis of Aminomethyl Cobalt Bis(dicarbollide) from the Low-Temperature Reaction of Bromomethyl Phtalimide with Lithiated Cs1, and Subsequent Cleavage of the Protective Groupa

a

Alternatively NaBH4 in i-PrOH-water can be used, followed by hydrolysis by 3M HCl in glacial acetic acid.

Therefore, in summary, the reactions of Br-(CH2)n-N(CO)2NC6H4 with lithiated cobalt bis(dicarbollide) under the described conditions do not give rise to expected alkylphtalimide products for n = 2 or 3 but do for n = 1, albeit in relatively low yield.

position of the cobalt bis(dicarbollide) cage. It is reasonable that here the lithiated cobalt bis(dicarbollide) acts as a sterically demanding nucleophile comparable in strength to phenyllithum. Further experimental and theoretical studies focus on the determination of pKa values of CH protons present in the cobalt bis(dicarbollide) cage and on elucidating the contribution of electronic effects introduced by the substituent on the cyclization process in both cobalt bis(dicarbollide) and carborane series. The formation of different cyclic moieties in anions 3− and 5− has no analogy either in the substitution chemistry of cobalt bis(dicarbollide) or in the chemistry of N-(ω-bromopropyl) phthalimides. The reaction pathways to both these compounds reasonably begin by the same nucleophilic attack as with the main isoindolone products and are detailed in Schemes 1 and 2. The substitution in 3− seemingly involves a closure to a triatomic ring, which resembles the ring formation in 5− (see Scheme 2). We assume a repetition of the nucleophilic attack on the same carbonyl by a second lithiated cage carbon atom with the formation of the bridge and a simultaneous extrusion of the aziridine ring. Considering the formation of 5− (see Scheme 2), the initial nucleophilic attack is followed by breakage of the (O)C−N bond in an intermediate species. The final step consists in a substitution of the terminal carbon atom present in the bromopropyl moiety by the NH2 group, which acts as another available nucleophile. Only in the case of lithiated Cs1 with N-(2-bromomethyl)phthalimide (see Scheme 3) did the reaction take place preferentially at the terminal -CH2Br moiety, leading to the isolation of the methyleneamino derivative Me4N6, but only in low overall yields, 18% or less, depending on the method of the cleavage of the respective (methylene)phthalimide intermediate product (see Scheme 3). The cleavage was accomplished either by treatment with ethylenediamine or by NaBH4 followed by acid hydrolysis with HCl in acetic acid. (Note that cleavage by the typical method of treatment with hydrazine hydrate did not provide the expected product.) In purifications of the (methylene)phthalimide intermediate, a substantial amount of unreacted starting material Cs1 (29%) was recovered, as well as smaller quantities of a disubstituted and even a trisubstituted species. These compounds could be removed by repeated chromatography.

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CRYSTALLOGRAPHIC AND COMPUTATIONAL STUDIES The molecular structures for 2−, 3−, 4−, and 5− as determined by single-crystal X-ray diffraction analyses are presented in Figures 2−5; for selected interatomic distances see the figure captions. The isoindolone-type species in Me4N2 and Me3NH4 (Figures 2 and 4) adopt an asymmetric tricyclic bent arrangement resembling a hand pointing outward from the cobalt bis(dicarbollide) cage. The lateral heterocyclic moieties in both structures are oriented toward the second, unsubstituted, dicarbollide ligand, whereas the phenyl rings are pointing toward the B(6)−H site of the substituted ligand. The angle between C1−C3−N1 is 116.1° and 111.4° for 2− and 4−, respectively, and therefore the six-membered ring isoindolone system in 4− is slightly more inclined toward the cage. The parameters of the cobalt bis(dicarbollide) cage itself are not exceptional. In the structure of Me4N3 a tetrahydrofuranone ring is attached directly to the cobalt bis(dicarbollide) cage in a bridging manner via a quarternaly carbon atom (Figure 3). The orientation of the dicyclic ring structure in Me4N3 is almost perpendicular to the cobalt bis(dicarbollide) cage. The presence of the bridge interconnecting the two cobalt bis(dicarbollide) cage carbon atoms in Me4N3 causes the pentagonal ligand planes connected to the cobalt atom to become inclined. The phenyl ring in Me4N5 also adopts an almost perpendicular orientation with respect to the cobalt bis(dicarbollide) cage (Figure 5). The carbon positions in the structures of the isoindolone derivatives 2− and 4− correspond to an eclipsed conformation close to a cisoid arrangement (gauche) with torsion angles between the carbon atoms in the {C2B3} ligand planes of 9.34(1)° and 11.00(1)°, respectively, which are even smaller than the value observed for the bridged derivative 3− that has an angle of 17.08(2)°. The position of the carbon atoms in the 5− anion is slightly different and adopts an even more eclipsed, but still gauche, conformation with a torsion angle of 6.25(2)°. 3152


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ments resulted in the geometries with almost ideal transoid arrangements of the CC vectors, the second starting geometries brought about a mutual rotation of the vectors to value for θ of ∼36°, for 6b− see Figure 6. Interestingly, the intermolecular N···H nonbonded distance is shorter in length than the sum of the corresponding van der Waals radii for these atoms, which might account for the distortions observed in 6b−. Such a N···H contact is missing in the neutral form 6a as well as in both transoid forms related to 6a and 6b−. The associated energies of the latter isomers lie above those with θ of ∼36° by ca. 1.5 kcal/mol. All these four structures were computed to be minima on their corresponding potential energy hypersurfaces at BP86/AE1. Computations also revealed that substitution on the cobalt bis(dicarbollide) carbon atom is reflected in the computed shielding tensor(s) to a small extent. The calculated 11B NMR spectrum (see Table 1) for 6b− is much more symmetrical than that for neutral 6a (cf. the corresponding peaks associated with B(8) and B(8′)) and is more-or-less shifted to lower frequencies with respect to 6a, obviously due to larger shielding of almost all B atoms in the presence of an overall delocalized negative charge. This is in accord with the experimental NMR pattern observed for Me4N6 (e.g., if the two quite discernible peaks for B(8) and B(8′) had existed in reality, we would have seen such a difference of ca. 5 ppm in the experimental data). In sum, both this NMR criterion and the absence of the stabilizing N···H contact support our conclusion that the correct structure is the anionic form 6b− that is present in neutral or slightly basic solutions of the methylene amine derivative. The experimental data and observations are thus in close relation to those for 6b− computed at the GIAO-B3LYP/II′ level.

With the aim to better interpret the structure and solution behavior of the methylene amine derivative of the cobalt bis(dicarbollide) ion 6−, quantum chemical computations at the BP86/AE1 level of theory were carried out. A density functional theory (DFT)-based refinement of the molecular structure of the monoanionic 1-CH2NH2 6b− form is presented in Figure 6; however, calculations also considered the

Figure 6. Optimized geometry at BP86/AE1 of 6b−. A dotted line indicates intramolecular N···H distance is 217 pm, i.e., shorter than than the sum of the van der Waals radii of N and H atoms (266 pm). The dihedral angles θ[B(8′)−Co−B(10)−B(8)] and θ [B(8)−Co− B(10′)−B(8′)] are 36° and 38.5°.

zwitterionic 1-CH2NH3 6a (not shown in Figure 6). The use of GIAO−DFT computational protocol (optimization of geometries at DFT levels and chemical shift computation at GIAO−DFT level) has proved successful for the parent cobalt bis(dicarbollide) ion51 and its monocarboxy and dicarboxy derivatives.32 A previous computational study revealed the parent compound to have an energy minimum in a structural form of C2h symmetry, that is, with the carbon atoms in both subclusters of the cobalt bis(dicarbollide) ion in the anti conformation, in which the rotational angle θ (defined as B8− Co3−B10−B8′) is 180°.51 Therefore, we started to optimize the molecular geometries of 6a and 6b− not only with the anti conformation of both CC pairs, in which the rotational angle θ (defined as B8−Co3−B10−B8′) is 180° as observed previously in parent ions (C2h-like forms(s)),51 but also from C2v-like form(s) when θ is 0°. Whereas the former starting arrange-

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CONCLUSIONS The results of our experiments thus indicate that the reactions of the lithiated cobalt bis(diarbollide) represent easy and efficient ways to conjoin cobalt bis(dicarbollide) cages with tricyclic isoindolone rings or other cyclic species with unusual structures. Their formation can be attributed to the general ability of the lithiated {Li−C} vertex to act as nucleophile preferentially at the carbonyl group, leaving the bromoalkyl moiety as an available site for subsequent cyclization reactions. Therefore, this observation may be applicable in a wider variety of future nucleophilic addition reactions of the lithiated ion 1− with various carbonyl functions to give secondary alcohols or other cyclic structures.

Table 1. Calculated 11B NMR Chemical Shifts (calcd.) at GIAO-B3LYP/II//BP86/AE1, in ppm, for Cobalt Bis(dicarbollide)-1CH2NH3, 6a, and Cobalt Bis(dicarbollide)-1-CH2NH2, 6b− B(8) 6a 6b−

calcd. Øa calcd. Øa

10.3 9.8

B(9)

6b− expb a

calcd. Øa calcd. Øa

B(10)

15.0

−3.1

B(10′) 3.5

B(4)

B(7)

−11.0

−0.5

−7.2

B(9′)

−1.7

−2.7

−2.2

2.1 B(12′) −0.9

−5.2

0.8 B(5)

B(11)

−25.1

−18.9

−1.8 −5.0

−6.5 −6.6

−2.2

9.4 9.6 7.1 B(12)

−4.5 −8.0

B(4′)

B(7′)

−2.0

−4.1

−6.6

−4.2

−4.4

12.7

expb 6a

B(8′)

−9.1

−5.0

B(5′)

−5.3 -5.6 B(11′)

B(6)

B(6′)

−19.4

−19.5

−21.6

−26.6

−19.8

−21.8

−26.7

−22.7

−21.5

−22.6

−20.7 −6.3

−21.6

−7.7 −7.3

−19.8 −20.8 −16.9

Ø represents mean calculated values compared with the experimentally determined chemical shifts. bThis work. 3153


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Table 2. Selected Crystallographic Data, Data Collection, and Structure Refinement Parameters for Compounds 2− to 5−a compound formula M (g mol−1) crystal habit crystal size (mm) crystal system space group a (Å) b(Å) c (Å) α (deg) β (deg) γ (deg) V (Å3) Z Dcalc (g mL−1) μ(Mo Kα) (mm−1) TFb diffrns total; Rint (%)c unique/obsdc diffrns R (%)d,e wR (all data) (%)e GOFe max/min Δρ (e Å−3) CCDC entry

Me4N2 C14H29B18CoNO2·C4H12N· CH2Cl2 655.96 orange-red prism 0.50 × 0.36 × 0.35 triclinic P1̅ 8.8476 (2) 12.0410 (3) 16.3218 (4) 82.3860 (10) 84.0090 (10) 72.5600 (10) 1640.42 (7) 2 1.328 0.71 0.718, 0.788 21 185, 0.018 7528/6677 0.045 0.122 1.03 1.66/−1.04 977760

Me4N3·CH2Cl2 2(C12H23B18CoO2)·2(C4H12N)· CH2Cl2 1138.85 orange prism 0.30× 0.22 × 0.06 monoclinic P21/c 7.330 10 (10) 32.8341 (8) 13.0658 (3)

Me3NH4 C15H31B18CoNO2· C3H10N 571.04 red plate 0.46 × 0.36 × 0.07 orthorhombic Pbca 9.4710 (2) 24.1214 (4) 28.5697 (5)

93.7400 (10)

Li(DME)5·H2O C15H31B18CoNO2·H2O·Li· DME 535.87 orange bar 0.40 × 0.17 × 0.12 monoclinic P21/n 11.0702 (4) 13.0078 (4) 22.9231 (9) 97.4450 (10)

3137.94 (11) 2 1.205 0.65 0.829, 0.965 18 320; 0.036 6133/4713 0.051 0.155 1.04 0.93/ −0.33 977761

6526.9 (2) 8 1.162 0.55 0.788, 0.964 28 083; 0.033 6409/5229 0.046 0.120 1.04 1.08/ −0.68 977762

3273.1 (2) 4 1.087 0.54 0.812, 0.939 47 670; 0.048 7511/5933 0.062 0.169 1.04 1.06, −0.75 977763

Common details: T = 150(2) K. bThe range of transmission factors. cRint = ∑|F02 − F02(mean)|/∑F02, where F02(mean) is the average intensity for symmetry-equivalent iffractions. dDiffractions with I0 > 2σ(I0). eR = ∑||F0| − |Fc||/∑|F0|, wR = [∑{w(F02 − Fc2)2}/∑w(F02)2]1/2. GOF = [∑(w(F02 − Fc2)2)/(Ndiffrs − Nparams)]1/2. a

purposes, the majority of the new derivatives of ion, compounds 2− to 6− were precipitated in the form of the respective Me4N+ salts that are not hygroscopic and were carefully dried at 60 °C for at least for 12 h to remove residual water or solvents before the measurements of melting points and analysis. The identity of all the reported compounds was also conclusively proven by their spectral data, which are fully in agreement with the crystal structures presented in this paper. Instrumental Techniques. 1H, 11B, and 13C NMR spectroscopy was performed on a Varian Mercury 400Plus instrument. 1H (400 MHz) and 13C NMR (100 MHz) chemical shifts are referred to the residual 1H signal(s) of a deuterated solvent used and are given in ppm. 1H NMR chemical shifts δ(1H) are given in ppm, coupling constants J(H,H) in Hz. δ (1H{11B}) data are presented, and their assignment is based on selectively decoupled δ(1H)−{11B selective}NMR experiments. 11B NMR (128 MHz) chemical shifts are given in parts per million to high-frequency (low field) to F3B·OEt2 as the external reference. Coupling constants 1J(11B−1H) were measured by resolution-enhanced 11B spectra with a digital resolution of 2 Hz and are given in Hz. The 11B NMR data are presented in the text below in the following format: 11B chemical shifts δ(11B) (ppm), multiplicity and coupling J(11B−1H) constants are given in Hz. The peak assignment is based on {11B−11B} COSY NMR spectroscopy and compared with the spectrum of the parent salt Cs1 (for assignment of the unsubstituted ligand). Only 13C{1H} NMR resonances are listed; the peak assignment is in full agreement with signal multiplicities observed in coupled 13C NMR experiments. Analytical HPLC was performed on Merck-Hitachi HPLC system LaChrom 7000 series equipped with a DAD 7450 detector (fixed wavelengths 260, 285, 290, and 308 nm) and an Intelligent Injector L7250. The chromatographic IP-RP procedure based on the methods previously reported56 for the separation of hydrophobic borate anions was applied by using a buffer containing 4.5 mmol/L hexylamine acetate in 58% aqueous CH3CN, pH 6.5. Column: RP Separon SGX C8, 7 μm (silica with chemically bonded octyl groups), Tessek Prague,

Interestingly, an aspect of these reactions is that the cyclic products form in a one-pot reaction, in good yields, and under the application of rather mild and simple reaction conditions. These novel derivatives along with similar isoindolinone analogues represent key structural frameworks in a diverse family of synthetic and naturally occurring bioactive molecules,39,41,44,52 with antiviral, antibiotics, antiinflamatory, antihypertensive, antidepressant, cytostatic, and numerous other actions. A potential use of cobalt bis(dicarbollide) ion as hydrophobic pharmacophore belongs now to newly emerging topics.4,5,12,53,54 Screening for the biological activity of the boron compounds described in this article is therefore currently in progress.

■

EXPERIMENTAL SECTION

The cesium salt of cobalt bis(1,2-dicarbollide) (Cs1) was purchased from Katchem Ltd., Czech Republic. The Cs1 salt was crystallized from hot aqueous ethanol (ca. 50%) and dried in vacuum for 4 h at 120 °C and then 8−12 h at 180 °C prior to use. Dimethoxyethane was dried with sodium diphenyl ketyl and distilled. Other chemicals and solvents were purchased from Aldrich and Lachner, Czech Republic, respectively, and were used without purification. Analytical thin-layer chromatography was carried out on Silufol silica gel on aluminum foil, with starch as the binder (Kavalier, Czech Republic). Unless otherwise specified, column chromatography was performed on a high-purity silica gel (Merck grade, Type 7754, 70−230 mesh, 60 Å), using acetonitrile−dichloromethane 1:3 as the mobile phase. All the reactions were performed using standard vacuum or inertatmosphere techniques under a high-purity argon (99.999%, MESSER) as described by Shriver55 although some operations, such as flash chromatography and crystallization, were performed in the air. Melting points were determined in sealed capillaries on a BŰ CHI Melting Point B-545 apparatus and are uncorrected. For analytic 3154


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Inorganic Chemistry Czech Republic. Capacity factors k′ = (tR − t0)/t0 (where tR is retention time, t0 is the void retention time of a nonretained peak) are given for individual compounds; k′ = 4.18 was observed for the parent unsubstituted cobalt bis(dicarbollide) ion, which was 4.16 under the same chromatographic conditions. The purity assay was based on the peak areas on the chromatograms of the individual compounds recorded at 285 nm. Mass spectrometry measurements were performed on a Thermo Finnigan LCQ-Fleet Ion Trap instrument using electrospray (ESI) ionization. Negative ions were detected. Samples dissolved in acetonitrile (concentrations ∼100 ng·ml−1) were introduced to the ion source by the infusion of 5 μL·min−1, source voltage 5.57 kV, tube lens voltage 49.8 V, capillary voltage 10.0 V, drying temperature at 188 °C, drying gas flow 8 L min−1, and auxiliary gas pressure 6 bar. In all cases negative ions corresponding to the molecular ion were observed with 100% abundance for the highest peak in the isotopic distribution plot. The isotopic distribution in the boron plot of all peaks is in perfect agreement with the calculated spectral pattern. The data are presented for the most abundant mass in the boron distribution plot of the base peak (100%) and for the peak corresponding to the highest m/z value with its relative abundance (%). X-ray Structure Determinations. Single-crystal X-ray diffraction data for the salts containing the anions 2−, 3−, 4−, and 5− were obtained from Nonius KappaCCD diifractometer equipped with Bruker ApexII-CCD detector by monochromatized Mo Kα radiation (λ = 0.710 73 Å). The structure was solved by direct methods and refined by full-matrix least-squares based on F2 (SHELXS; SHELXL97 Sheldrick, 2008).57 The hydrogen atoms were fixed into idealized positions (riding model) and assigned temperature factors Hiso(H) = 1.2Ueq(pivot atom). The crystallographic data are given in Table 2. PLATON/SQUEEZE was used to correct the data of Me3NH4 for the presence of the disordered solvent. PLATON/SQUEEZE was used to correct the data of Li(DME)5·H2O for the presence of the disordered solvents occurring in the void of unit cell as well as in coordination sphere of Li+ cation. Computational Details. Stationary points were optimized at the BP86/AE1 level, that is, by employing the exchange and correlation functional of Becke58 and Perdew,59 respectively, and all-electron the basis of the augmented Wachter’s basis60 on Co and 6-31G* basis on all other elements.61,62 Magnetic shieldings were computed for BP86/ AE1 geometries by employing gauge-including atomic orbitals (GIAOs),63−65 the B3LYP66 hybrid functional, together with basis II′ (the same Wachters’ basis set on Co as described above, a TZP basis set on C, B, N together with a DZ basis set on H by Huzinaga).67 Gaussian suit of programs68 was utilized for all computations. Synthetic Procedures. (Oxazolo[2,3-a]isoindol-5(9-b-H)-1,2,3dihydro-9-b-yl)-(1-cobalt(III) Bis(1,2-dicarbollide)(1−), Tetramethylammonium Salt (Me4N2) and Bridged Derivative (Tetrahydro-2benzo[4,5]furan-1(3H)-1-[3,3]-yl-)-1,1′-μ-cobalt(III) Bis(1,2dicarbollide)(1−), Tetramethylammonium Salt (Me4N3). A perfectly dried (185 °C, 12 h in vacuum) cesium salt of cobalt bis(dicarbollide) (2.75 g, 5.98 mmol) was dissolved under agron in dimethoxyethane (DME, 40 mL), cooled under stirring to −82 °C (bath temperature), reacted with BuLi (4.1 mL, 1.6 M in hexane; 6.6 mmol), left to warm slowly to room temperature, and cooled again. N-(2-bromoethyl)phthalimide (1.61 g, 6.32 mmol) in 10 mL of DME was then added slowly from a syringe for 15 min at −82 °C; the reaction mixture was stirred in the bath for 1 h and left to warm to room temperature for 2 h. The reaction was quenched by the addition of methanol (1 mL); the water (2 mL) and the solvents were removed in vacuum. The crude product was dissolved in MeOH and precipitated by aqueous CsCl. The precipitate was crystallized from hot aqueous 50% MeOH. The solids were collected, dried, and dissolved in a CH2Cl2−CH3CN mixture (3:1, b.v.) and injected atop a silica gel column (2.5 × 25 cm). Elution using mobile phase of the same composition led to recovery of the starting Cs1 (430 mg, 16%), which contained some Cs3. Subsequent elution with the same mixture of solvents followed by the evaporation of solvents under reduced pressure led to isolation of a red band that, according to HPLC, contained the crude isoindolone derivative that still contained some starting Cs1 and the second

product Cs3 present in smaller quantity up to 10%. These solids were dissolved in hot 20% aqueous EtOH and precipitated by an excess of aqueous Me4NCl. After the mixture cooled and stood overnight, the crude product was collected and dried. The red solid was dissolved in a CH2Cl2−CH3CN mixture (85:15, b.v.), injected atop a silica gel column (3.5 × 35 cm), chromatographed by the same composition of the solvents as the mobile phase, and finally eluted with an increase in the CH3CN content to 4:1 b.v. After removing the solvent and drying it in vacuum, the second main red-orange band contained pure Me4N2; 2.20 g (64%). The crystals of Me4N2 for X-ray diffraction were grown from CH2Cl2−hexane (with a drop of MeOH for dissolution). The front orange band was collected separately and evaporated; the solid was extracted with CH2Cl2 (4 × 5 mL), and the extract was layered with hexane and left to crystallize. The crystals of the bridge product Me4N3 (180 mg, 6%), suitable for X-ray diffraction, were collected. Me4N2: Found: Rf (CH2Cl2/CH3CN 3:1) 0.43; mp 178−180 °C; HPLC: k′ 4.07, purity assay 99.6%; Analysis found: C 37.8, H 7.0, calcd. for C18H41B18CoN2O2: C 37.9, H 7.2%; 1H NMR δH(400 MHz; acetone-d6), 7.79 (2H, br. dd, J 6.4, ArH), 7.66 (2H, br. dd, J 6.4, ArH), 4.557 (1H, br s, CH carborane), 4.315 (1H, br. t, J 6.4, −CH2O−), 4.161 (3H, m, −CH2N− and −CH2O−), 4.122 (1H, s, CHcarborane), 3.869 (2H, s, CHcarborane), 3.451 (12H, s, Me4N+), δB-H (from 1H-{11B} selective NMR experiments) 4.08, 3.72 (2H, 2s, B(8, 8′)H), 3.04 (2H, s, B(10)H), 2.88 (2H, s, B(10′)H), 2.23, 2.13 (2H, 2s, B(4, 7)H), 3.03, 2.99, 2.60, 2.54, 1.90 (6H, 5s, B(4′, 7′, 9,12, 9′, 12′)H), 1.96 (1H, s, B(5)H), 1.46 (1H, s, B(11)H), 1.57, 1.51 (2H, 2 s, B(5′, 11′)H), 1.66 (2H, s, B(6,6′)H); 11B NMR δB(128 MHz; acetone-d6; Et2O·BF3) 6.06 (2B, br. d, J 149, B8, 8′), 2.11 (1B, br. d, J 143, B10′), 0.59 (1B, br. d, J 146, B10), −3.19 (2B, d, J 137, B4, 7), −4.62 (2B, d, J 131, B4′, 7′), −7.90 (6B, 3d, overlap, B4′, 7′, 9,12, 9′, 12′), −13.63 (1B, d, J 161, B5), −16.32 (1B, d, J 156, B11), −17.31, −18.38 (2B, 2d, J 150, 143, B5′, 11′), −21.33 (2B, d, J 159, B6,6′); 13 C{1H} NMR δC(100 MHz; acetone-d6) 171.04 (1C, CO), 146.3 (1C, C), 134.64 (1C, ArC), 132.13 (2C, ArC), 125.20 (1C, ArC), 124.61 (1C, ArC), 104.28 (1C, Cquart.), 73.67 (1C, OCH2), 72.05 (1C, Ccarborane), 57.98 (1C, CHcarborane), 56.01 (4C, Me4N+), 53.06 (1C, CHcarborane), 50.48 (1C, CHcarborane), 44.35 (1C, CH2N); m/z (ESI−) 500.50 (M−, 10%), 497.58 (100%), calcd. 497.33 and 500.32. Me4N3 Found: Rf (CH2Cl2/CH3CN 3:1) 0.45; mp 260−261 °C, HPLC: k′ 5.92, purity assay 95.4% (the rest was unreacted ion 1−); analysis found C 36.0, H 6.6, calcd. for C16H36B18CoO2N: C 36.4, H 6.9; 1H NMR δH(400 MHz; acetone-d6), 7.96 (1H, dd, J 7.6, ArH), 7.89 (2H, m, ArH) 7.79 (1H, m, ArH), 5.71 (1H, br s, CHcarborane), 5.63 (1H, s, CHcarborane), 3.47 (12H, s, Me4N+), δB-H (from 1H-{11B} selective NMR experiments) 4.08, 3.72 (2H, 2s, B(8, 8′)H), 3.04 (2H, s, B(10)H), 2.88 (2H, s, B(10′)H), 2.23, 2.13 (2H, 2s, B(4, 7)H), 3.03, 2.99, 2.60, 2.54, 1.90 (6H, 5s, B(4′, 7′, 9,12, 9′, 12′)H), 1.96 (1H, s, B(5)H), 1.46 (1H, s, B(11)H), 1.57, 1.51 (2H, 2 s, B(5′, 11′)H), 1.66 (2H, s, B(6,6′)H); 11B NMR δB(128 MHz; CD3CN; Et2O·BF3) 6.77 (2B, br. d, J 149, B8, 8′), 0.44 (2B, br. d, J 143, B10,10′), −2.36 (2B, d, J 137, B4, 7), −3.67 (2B, 2d, J 131, B4′, 7′, 9,12), −6.23 (2B, d, overlap, B 9′, 12′), −16.27 (2B, d, J 161, B5, 11), −18.10 (1B, d, J 156, B5′, 11′), −23.26 (2B, d, J 159, B6,6′); 13C{1H} NMR δC(100 MHz; acetone-d6) 166.77 (1C, CO), 145.53 (1C, C), 135.84 (1C, ArC), 132.25 (1C, ArC), 126.47 (1C, ArC), 126.36 (1C, ArC), 125.17 (1C, ArC), 92.63 (1C, Cquart.), 58.26 (2C, Ccarborane), 56.0 (4C, Me4N+), 54.91 (1C, CHcarborane), 53.84 (1C, CHcarborane); m/z (ESI−) 457.42 (M−, 12%), 454.42 (100), calcd. 457.28 and 454.28. 1-(2H-[1,3]Oxazino[2,3-a]isoindol-6(10-b-H)-1,3,4-dihydro-10-byl)-cobalt(III) Bis(1,2-dicarbollide), Cesium and Tetramethylammonium Salts (Cs4 and Me4N4) and (2-(Azetidin-yl-carbonyl)benzoyl)-1-cobalt(III) Bis(1,2-dicarbollide)(1−), Cesium and Tetramethylammonium Salts (Cs5 and Me4N5). The Cs1 (2.28 g, 5.0 mmol) in DME (40 mL) was reacted with BuLi (2.3 mL, 2.5 M in hexane; 5.75 mmol) N-(3-bromopropyl)phthalimide (1.56 g, 5.81 mmol, dissolved in 10 mL of DME) under identical conditions described above for the compounds 2− and 3−. The reaction mixture was left overnight to warm slowly to room temperature. The first workup was made analogously to the above procedure for compounds 2− and 3−. The 3155


Article

Inorganic Chemistry mixture of cesium salts was dissolved in CH2Cl2−CH3CN (4:1, b.v.) and injected atop a silica gel column (3.5 × 30 cm). Slow elution using mobile phase of the same composition led to the recovery of an orange band containing the starting Cs1 (490 mg, 18%). Subsequent elution with CH2Cl2−CH3CN (3:1, b.v.), followed by the evaporation of solvents under reduced pressure, gave rise to the isolation of a red band, which, according to HPLC, contained the two main products present in the ratio of ca. 4:3. Continued elution with CH2Cl2− CH3CN (1:1 b.v.) resulted in the isolation of main part of collecting poorly resolved band eluting after the main part, and the effluent was evaporated. The crystals suitable for X-ray diffraction were grown from a small part of these solids dissolved in CH2Cl2 and layered by hexane. Crystals of DMELi5 crystallized from this crude fraction. The solids were then dissolved in aqueous MeOH, and the product was precipitated by addition of CsCl yielding Cs5 (780 mg). The first red collected band was separated once more by chromatography on a silica gel column (2.5 × 25 cm) using CH2Cl2−CH3CN (85:15 to 4:1 b.v.) as the mobile phase. Collected fractions were analyzed by HPLC. Pure fractions were combined, and the mixed ones were repeatedly chromatographed. This procedure gave Cs4 in an overall yield of 900 mg and an additional quantity of Cs5 (230 mg). One-third of each product was dissolved in aqueous methanol and precipitated by an excess of aqueous Me4NCl to obtain essentially quantitative conversion to Me4N4 and Me4N5 used for analytical purposes. Because of experimental difficulties in growing crystals suitable for crystallography directly from Me4N4, another portion of Cs4 was converted to trimethylammonium salt by metathesis. This salt crystallized from CH2Cl2−hexane (with a drop of MeOH for dissolution) provided crystals of a good shape and size, which were subsequently used in the X-ray diffraction analysis. Cs4. Yield 0.90 g (28%); Me4N4: Found: Rf (CH2Cl2/CH3CN 3:1) 0.19; mp 212−214 °C; HPLC: k′ 4.26, purity assay 100%; analysis: found C 38.8, H 7.3, calcd. for C19H43B18CoN2O2: C 39.0, H 7.4%; 1H NMR δH(400 MHz; acetone-d6), 7.815 (1H, br. t, J 7.6, ArH), 7.686 (1H, d, J 7.6, d, ArH), 7.629 (1H, d, J 7.6, d, ArH), 4.707 (1H, s, CHcarborane), 4.575 (1H, s, CHcarborane), 4.155 (1H, t, J 11.2, −CH2O−), 3.982 (1H, s, CHcarborane), 3.682 (1H, t, J 11.2, −CH2O−), 3.459 (12H, s, Me4N+), 3.315 (1H, m, J 5.6 −CH2N−), 2.858 (1H, m, J 6.4, −CH2N−), 2.102 (1H, m, J 6.4, −CH2CH2CH2−), 1.808 (1H, m, J 6.4, −CH2CH2CH2−); δB-H (from 1H-{11B} selective NMR experiments) 4.14, 3.73 (2H, 2s, B(8, 8′)H), 3.07 (2H, s, B(10)H), 2.07 (2H, s, B(10′)H), 2.21, 2.14 (2H, 2s, B(4, 7)H), 3.32, 3.19, (2H, s, B(9, 12)H), 2.65, 2.55, 1.91 (4H, 3s, B(4′, 7′, 9′, 12′)H), 1.74 (1H, s, B(5)H), 1.37 (1H, s, B(11)H), 1.57, 1.56 (2H, 2 s, B(5′, 11′)H), 1.74 (2H, s, B(6,6′)H); 11B NMR δB(128 MHz; CD3CN; Et2O·BF3) 6.13 (2B, br. d, J 149, B8, 8′), 2.37 (1B, br. d, J 143, B10′), −0.10 (1B, br. d, J 146, B10), −2.98 (2B, d, J 137, B4, 7), −4.72 (2B, d, J 131, B4′, 7′), −5.57, −9.47 (2B, 2d, J 134, B9,12), −6.80, −7.90, (4B, 2d, overlap, B4′, 7′, 9′, 12′), −12.76 (1B, d, J 161, B5), −16.27 (1B, d, J 156, B11), −17.46, −18.50 (2B, 2d, J 150, 143, B5′, 11′), −21.69 (2B, d, J 159, B6,6′); 13C{1H} NMR δC(100 MHz; acetone-d6) 169.11 (1C, CO), 144.85 (1C, ArC), 134.64 (1C, ArC), 133.46 (1C, ArC), 131.39 (1C, ArC), 124.22 (1C, ArC), 124.18 (1C, ArC), 98.66 (1C, Cquart.), 72.59 (1C, Ccarborane), 60.69 (1C, CHcarborane), 57.82 (1C, CH2O), 56.00 (4C, Me4N+), 54.03 (1C, CHcarborane), 50.99 (1C, CHcarborane), 35.00 (1C, CH2); 24.09 (1C, CH2); m/z (ESI−) 514.42 (M−, 12%), 511.50 (100), calcd. 514.34 and 511.35. Cs5. Yield 1.01 g (31%), Me4N5: Found: Rf (CH2Cl2/CH3CN 3:1) 0.12; mp 189−191 °C; HPLC: k′ 2.98, purity assay 97.8%; Analysis found C 39.2, H 7.5, calcd. for C19H43B18CoN2O2C: 39.00, H 7.4%; 1 H NMR δH(400 MHz; acetone-d6), 8.437 (1H, d, J 7.6, ArH), 7.570 (1H, t, J 7.2, ArH), 7.497 (1H, t, J 7.6, d, ArH), 7.284 (1H, d, J 7.6, d, ArH), 4.233 (2H, s, CHcarborane), 4.106 (1Heq, q, J 7.2, −CH2N−), 3.945 (1Heq, q, J 6.0, −CH2N−), 3.821 (2Hax, m, −CH2N−), 3.583 (1H, s, CHcarborane), 3.451 (12H, s, Me4N+), 2.296 (1H, m, −CH2CH2CH2−), 2.214 (1H, m, −CH2CH2CH2−); δB-H (from 1H{11B} selective NMR experiments) 3.96, 3.73 (2H, 2s, B(8, 8′)H), 3.05 (2H, s, B(10)H), 2.95 (2H, s, B(10′)H), 2.19 (2H, s, B(4, 7)H), 3.10, (2H, s, B(9, 12)H), 2.61, 2.53, 1.87 (5H, 3s, B(4′, 7′, 12′, 9′, 12′)H), 1.74 (1H, s, B(5,11)H), 1.59, 1.42 (2H, 2 s, B(5′, 11′)H), 1.75 (1H, s,

B(6)H), 1.59 (1H, s, B(6′)H); 11B NMR δB(128 MHz; CD3CN; Et2O.BF3) 7.46 (2B, br. d, J 150, B8, 8′), 2.85 (1B, br. d, J 140, B10′), 0.87 (1B, br. d, J 143, B10), −4.43 (3B, d, J 136, B4, 7,9), −5.43 (2B, d, J 132, B4′, 7′), −6.57, −7.52 (3B, 2d, J 144 B12, 9′, 12′), −15.30 (2B, d, J 159, 5,11), −16.49, −17.72 (2B, 2d, J 148, B5′,11′), −19.32 (2B, d, J 143, B6); −22.95 (2B, d, J 171, B6′); 13C{1H} NMR δC(100 MHz; acetone-d6) 194.55 (1C, CO), 172.14 (1C, CO), 139.23 (1C, ArC), 135.78 (1C, ArC), 132.79 (2C, ArC), 128.47 (1C, ArC), 128.09 (1C, ArC), 71.35 (1C, Ccarborane), 56.02 (4C, Me4N+), 55.94 (1C, CHcarborane), 55.57 (1C, CHcarborane), 55.22 (1C, CHcarborane), 51.81 (1C, CH2N), 48.85 (1C, CH2N), 16.25 (1C, CH2); m/z(ESI−) 514.42 (M−, 14%), 511.50 (100), calcd. 514.34 and 511.35. (Methyleneamino)-1-cobalt(III) Bis(1,2-dicarbollide), Tetramethylammonium Salt (NMe46). The cesium salt of cobalt bis(dicarbollide) (2.71 g, 5.9 mmol) was dissolved under agron in DME (40 mL), cooled to −78 °C (bath temperature), and then BuLi (4.0 mL, 1.6 M in hexane; 6.4 mmol) was added from a syringe under vigorous stirring. After it was stirred for 15 min at low temperature, the reaction mixture was left to warm to room temperature and then cooled again. Solution of N-(1-bromomethyl)phthalimide (1.50 g, 6.2 mmol) in 15 mL of DME was then added slowly from a syringe for 15 min at −78 °C, and the reaction mixture was left to warm to room temperature for 4 h. After the mixture stood overnight, the solids were filtered under argon and washed with DME (2 × 10 mL), and a red combined filtrate was evaporated in vacuum. Solid residue was dissolved in a CH2Cl2− CH3CN mixture (85:15, b.v.) and injected atop a silica gel column (2.5 × 25 cm). Elution using the mobile phase of the same composition led to the recovery of an orange band containing the starting anion 1−, precipitated as a cesium salt (780 mg, 29%). Subsequent elution with the same mixture of solvents in the ratio 3:1 to 1:1 b.v. led to the isolation of a red band corresponding to a phthalimide product. After the evaporation of volatiles under reduced pressure, this product was precipitated by an excess of aqueous Me4NCl, and the precipitate was then dried and crystallized from CH2Cl2−hexane (to which a few drops of MeOH were added); yield 1.95 g, (59%). Last fractions from chromatography contained an unseparable mixture of disubstituted and trisubstituted species (yield ca. 10%), which were identified by MS. 500 mg (1.04 mmol) of the above intermediate was dissolved in 10 mL of n-butanol; ethylenediamine (1.0 mL) was added, and the reaction mixture was heated and stirred at 95 °C under nitrogen for 6 h. After the mixture cooled, the volatiles were removed under reduced pressure (heated in a bath at temperature 80 °C). The residue was dissolved in ether and washed with diluted HCl (3 M, 3 × 30 mL); while the organic phase was washed with water and evaporated to water and precipitated by Me4NCl, the solids were collected and dried. The product was separated from the parent ion 1−, which resulted from the reaction as a byproduct of chromatography on silica gel using the solvent mixture CH2Cl2−CH3CN (4:1, b.v.); yield 110 mg (30%). Alternatively, a reduction procedure using NaBH4 was used. 500 mg (1.04 mmol) of the above intermediate was dissolved in isopropanol− water (5:1 b.v., 30 mL), then NaBH4 (300 mg, 8 mmol) was added, and the slurry was stirred and heated at 65 °C for 4 h. The solvents were removed in vacuum, and the solids were treated with water (25 mL). The red extract was decanted, and the solids were washed with 30% aqueous MeOH (10 mL). Combined extracts were evaporated almost to dryness; then, 2 M HCl in glacial acetic acid (20 mL) was added, and the reaction mixture was heated for 4 h at 85 °C. The residue was dissolved in ether and washed with diluted HCl (3 M, 3 × 30 mL); while the organic phase was washed with water and evaporated to water and precipitated by Me4NCl, the solids were collected and dried. The product was separated by repeated chromatography on silica gel using the solvent mixture CH2Cl2− CH3CN (9:1 to 4:1, b.v.) as an orange band; yield 65 mg, 18%. Me4N6: Found: Rf (CH2Cl2/CH3CN 3:1) 0.31; HPLC: k′ 4.36, purity assay 98.1%; Analysis found: C 24.9, H 8.5, calc. for C9H37B18CoN2: C 25.3, H 8.7%; 1H NMR (400 MHz; CD3CN, Me4Si) δH/ppm, 4.322 (1H, d, J = 14,4 Hz, CH2NH2), 4.069 (1H, br.s, CH carborane), 4.03 (1H, br.s, CHcarborane), 3.884 (1H, br.s, CHcarborane), 3.822 (1H, d, J= 14.4 Hz, -CH2-NH), 3.46 (12H, 3156


Article

Inorganic Chemistry

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Me4N+), δB-H (from 1H-{11B} selective NMR experiments): 3.501, 3.258 (2H, 2s, B(8,8′)H), 2.979, 2.918 (2H, 2s, B(10,10′)H); 2.841, 1.828, 1.811 (8H, s, B(4,7,4′,7′,9,12, 9′,12′)H); 1.645 (1H, 1s, B(6′) H), 1.592 (1H, s, B(6′)H), 1.595, 1.592 (4H, 5s, B(5, 11, 5′,11′)H); 11 B NMR (128 MHz; CD3CN; Et2O·BF3) δB/ppm: 7.05 (2B, d, J = 144 Hz, B8,8′), 2.13, 0.774 (2B, 2d, J = 159 and 158 Hz, B10,10′), −5.60, −6.55, −4.22 (8B, 3d, overlap, B4,7,4′,7′,9,12,9′,12′), −16.92 (4B, d, J = 162 Hz, B5,11, 5′,11′), −21.51 (1B, d, J = 147 Hz, B6), −22.63 (1B, d, J = 159 Hz, B6′); 13C{1H} NMR (100 MHz; CD3CN; Me4Si) δC/ppm: 66.65 (1 C, Ccarborane), 53.85 (1 C, CHcarborane), 52.05 (1 C, d, CHcarborane), 51.81 (1 C, CHcarborane), 38.22 (1 C, CH2NH); m/ z (ESI−) 353.42 (100%), 356.42 (10%), calcd: 353.31 (100%), 356.30 (10%) [M−H]−.

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ASSOCIATED CONTENT

S Supporting Information *

Additional information is available: CIF file containing X-ray structural data for salts of the species 2−, 3−, 4−, and 5− and Cartesian geometries (xyz in Å) at PB86/AE1 for compounds 6b− and its zwitterionic form 6a. This material is available free of charge via the Internet at http://pubs.acs.org. Crystallographic data (excluding structure factors) for the structures of the salts of 2−, 3−, 4−, and 5− were deposited with the Cambridge Crystallographic Data Centre with CCDC Nos. 977760−977763. Copies of the data can be obtained, free of charge, on application to Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K. (fax: +44(0)1223-336033 or e-mail: [email protected]).

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AUTHOR INFORMATION

Corresponding Author

*Phone: (+420) 266173120. Fax: (+420) 220940161. E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by Grant Agency of the Academy of Sciences of the Czech Republic (Project IAAX00320901) and in part by Grant Agency of Czech Republic (Project 1505677S) and Research Plan RVO 61388980 awarded by the Academy of Sciences of the Czech Republic.

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REFERENCES

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