Icosahedral carboranes as scaffolds for congested regioselective polyaryl compounds: the distinct distance tuning of C–C and its antipodal B–B

Icosahedral carboranes as scaffolds for congested regioselective polyaryl compounds: the distinct distance tuning of C–C and its antipodal B–B

Scientific Highlights Biomaterials and materials for drug delivery, therapy, diagnostics and sensing 13 September 2019 93 hits icmabcsic

Four-fold aryl substituted o-carborane derivatives with defined patterns of substitution at the antipodal region of the cluster carbon atoms have been achieved. It is proven that this region is congested but lacks steric hindrance. Also, the two antipodal sites Cc–Cc and B9–B12 are affected very distinctly by electron donor substituents.

The closo C2B10H12 icosahedral carboranes, o-(1,2), m-(1,7), or p-(1,12), are the most widely studied boron clusters; they can be functionalized by different reactions,1 in a regioselective manner, with many possible sites of substitution. o-Carborane, 1,2-closo-C2B10H12, acts as a strong electron-withdrawing molecule through the substitution on the carbon, Cc,2 and as an electron-donating moiety through the boron vertices with a gradation depending on the distance to the carbon atoms.3 On the other hand, it is well known that the Cc–Ccbond length in o-carborane and metalla-o-carborane strongly depends on the electronic nature of the immediate Cc-substituents;4 π-donor substituents bonded to the Cc, as well as atoms with lone pairs, donate electron density to the σ*(Cc–Cc) antibonding orbital (negative hyperconjugation) of o-carborane, which lies in the Cc–Cc bond, increasing significantly the Cc–Cc bond distance.5 In the case of aryl substituents, the orientation of the substituents has a significant impact on the electron donation.6 The longest Cc–Cc distance ever reported is 2.156(4) Å for the 1,2-(CR2Fc)2-1,2-closo-C2B10H10, {R = pentamethylene; Fc = (η5-C5H4)Fe(η5-C5H5)} o-carborane cluster derivative.7 While the plasticity of the Cc–Cc bond has been investigated, the possibility of a similar behaviour at the B–B bonds located antipodal to the cluster carbon atoms remained unexplored.In addition, if π-aromaticity and tridimensional aromaticity of the icosahedral boranes are two sides of the same coin,8 could it be possible to obtain hybrid polyaryl compounds by merging the 2D organic aromatic groups at the dense antipodal region of the cluster carbon atoms with 3D inorganic icosahedral clusters?To produce B–C substitutions, a useful and general method is by electrophilic iodination of o-carborane followed by Kumada cross-coupling reaction.9 This implies that one should start from the appropriate iodocarborane derivatives. A less regioselective B(8)/B(9)-aryl-o-carborane Pd-catalysed monoarylation with aryl iodides via B–H activation was reported,10 as well as a palladium-catalysed regioselective diarylation on B(4,5) of o-carborane directly from B–H with aryl halides, with the help of the traceless directing carboxylic group.11 With hindered substitutions on the neighbouring C/B atoms, 3-Ph-1,2-Ph2-1,2-closo-C2B10H9 and 3,6-Ph2-1,2-Ph2-1,2-closo-C2B10H912 derivatives were obtained in low yield by using the sequential nucleophilic-capping reactions of BPhCl2 in the precursors [7,8-Ph2-7,8-nido-C2B9H9]2− and [6-Ph-7,8-Ph2-7,8-nido-C2B9H8]2−. It should be noted that disubstituted 9,12-Ph2-1,2-closo-C2B10H10,13 1,9- and 1,12-(p-MeC6H4)2-1,2-closo-C2B10H10 were also reported.14 We interpret that the presence of the four phenyl groups in the crowded area adjacent to the Cc vertices is accessible because of the different behaviour of all the atoms connected to the C2B2 region where the strong electron-withdrawing (Cc) and electron-donating moieties (B) of the o-carboranyl group co-exist. As mentioned, it was our main target to elucidate if the four iodo groups in the compact and electron-rich region of the o-carborane cluster (Chart 1) could be fully or only partially replaced by the organic aryl (sp2) groups such as phenyl to produce a “four phenyl congested site”. Furthermore, it could provide a good picture of the B–B tuning possibility to the antipodal Cc–Cc unit. This would be a potentially useful heavily congested electron-rich region due to the regioselective formation of B–C(sp2), B–C(sp) and B–C(sp3). To achieve so, the cross-coupling reaction on the B-iodinated o-carboranes with Grignard reagents in the presence of the Pd(ii) and Cu(i) catalysts was studied. Two were the starting iodinated derivatives, 9,12-I2-1,2-closo-C2B10H10 (1) and 8,10,9,12-I4-1,2-closo-C2B10H8 (2). In 2, the four iodo groups occupy a highly dense region antipodal to the Cc–Cc atoms. In 1, only two adjacent iodo groups are present, again antipodal to the Cc–Cc unit. Four Grignard reagents were used, phenylethynyl magnesium, phenyl magnesium and allyl magnesium chlorides, and 4-benzaldehyde dimethyl acetal magnesium bromide. The first, the second and the fourth would produce a highly electron dense and congested region in o-carborane derivatives, whereas the third would produce a more relaxed space. In a typical experiment, 1 and cis-[PdCl2(PPh3)2] and CuI as catalysts were dispersed in anhydrous THF and treated with the appropriate Grignard reagent at low temperatures (Scheme 1). After refluxing overnight, the corresponding crude compounds were purified (see ESI). The cross-coupling reaction of 1 with 4-benzaldehyde dimethyl acetal magnesium bromide proceeded to give 9,12-(C6H4CH(OCH3)2)2-1,2-closo-C2B10H103, in 71% yield (Scheme 1a), which was confirmed by multinuclear NMR, FTIR, mass spectrometry and elemental analysis.

Icosahedral carboranes as scaffolds for congested regioselective polyaryl compounds: the distinct distance tuning of C–C and its antipodal B–B

Related Topics: Biomaterials and materials for drug delivery, therapy, diagnostics and sensing

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