Quantitative syntheses of permethylated closo-1,10-R2C2B8Me8 (R = H, Me) carboranes. Egg-shaped hydrocarbons on the Frontier between inorganic and organic chemistry

Electrophilic methylation of the closo-1,10-R2C2B8H8 (1) (R = H or Me) dicarbaboranes at higher temperatures or thermal rearrangement of the 1,6-R2C2B8Me8 (3) compounds at 400–500 °C generated the B-permethylated derivatives closo-1,10-R2C2B8Me8 (2) in quantitative (>95%) yields. The compounds exhibit extreme air stability as a consequence of a rigid, egg shaped hydrocarbon structures incorporating inner 1,10-C2B8 carborane core.


Introduction
Methods for cage substitution on the cage of closo-1,10-C 2 B 8 H 10 (1a) generally parallel those employed for the larger C 2 B 10 H 12 icosahedral carboranes. 1 The CH hydrogens in 1a are sufficiently protonic in character to undergo lithiation with butyllithium in ethereal solvents, generating the mono-and dilithio derivatives. 2 The C-lithiated species afford the main entry to alkyl, aryl, carboxyl, silyl, and other C-substituted derivatives via treatment with appropriate reagents. For example, exopolyhedral metal complexes, 3,4 and the silyl-linked mixed-carboranes 5 have also been prepared by this route along with numerous C-metallated compounds containing main-group metals. 1 The only B-substitution processes so far reported are, however, the direct reaction between 1a and Cl 2 affording the Bperchloro species 1,10-H 2 C 2 B 8 Cl 8 (ref. 2) and those leading to a series of halo derivatives 1,10-H 2 C 2 B 8 H 7 -2-X. 6 The successful B-methylation experiments in the 12-vertex carborane series, [7][8][9] together with those achieved by our group in the B-methylation of closo-1,6-C 2 B 8 H 10 , 10 arachno-6,9-C 2 B 8 H 14 , 11 prompted us to extend boron-methylation strategy to the most stable members of the 10-vertex closo series, closo-1,10-R 2 C 2 B 8 H 10 (1) (where R ¼ H or Me), which have been now relatively easily available. 12 In this article we would like to present electrophilic reactions with methylation agents leading to quantitative permethylation of Bvertexes under the formation of rigid, hydrocarbon-boron structures of egg shape that exhibit outstandingly high stability.

Results and discussion
The electrophilic CH 3 I/AlCl 3 methylation of carborane closo-1,10-H 2 C 2 B 8 H 8 (1a) (Scheme 1) led on heating at 115 C for 15 h to exclusive formation of the B-permethylated dicarbaborane closo-1,10-H 2 C 2 B 8 Me 8 (2a) in practically quantitative yield (>95%). The scheme also shows that the CH 3 OTf/HOTf (Tf ¼ SO 2 CH 3 ) methylation proceeded excellently at 165 C for 48 h, giving again a quantitative yield of 2a (>95%). It is, however, interesting that the CH 3 I/AlCl 3 methylation (115 C, 15 h) of closo-1,10-Me 2 C 2 B 8 H 8 (1b) has completely failed, while the CH 3 OTf/HOTf methylation of 1b proceeded smoothly at 175 C for 48 h, giving again a quantitative yield of the decamethylated closo-1,10-Me 2 C 2 B 8 Me 8 (2b). This nding is in accord with that observed in the comparable 12-vertex closo-1,12-Me 2 C 2 B 10 Me 10 series (reux, 20 h, 91% yield). 9 As also observed for the latter species, an attempt at methylating the CH1,10 vertexes in 2a via the Li 2+ salt as in Scheme 1 has failed, too. The difficulty in forcing this reaction to completion must be due to the relative lack of reactivity of the CH vertices present in 2a, which is exacerbated by the steric protection afforded to each CH vertex by the methyl groups of the four surrounding BMe, vertices.
Another straightforward route leading to quantitative formation of permethylated dicarbaboranes 2 consists in thermal isomerisation of closo-1,6-R 2 C 2 B 8 Me 8 (3) carboranes (R ¼ H 3a or Me 3b) 10 by heating at 400-500 C in a sealed tube for 2 h. A similar thermal isomerisation principle could be also applied to the substituted derivatives, for example to closo-1,6- 10 which underwent cage rearrangement to afford 97% of the closo-1,10-H 2 C 2 B 8 Me 7 -2-OTf (5a) upon a similar heating, as shown in Scheme 2.
The structures of derivatives 2a and 5a were determined by an X-ray diffraction study (see Fig. 1 and 2). Both carboranes adopt the expected bicapped Archimedean antiprismatic geometry with two unsubstituted apical CH1,10 vertexes along with eight or seven BMe groups, respectively. The structure 5a unambiguously conrms the B2-substitution with the O-SO 2 -CF 3 group and permethylation in all other B-positions of the cluster. Unfortunately, the crystals of the permethylated 2b were not found suitable for crystallographic studies and the 2a/2b pair was therefore geometry optimized at the MP2/TZVP level ( Fig. 3 and 4).
The optimization revealed that the comparable B-B, C-B, and B-Me bonding vectors are very similar to those found crystallographically for 2a and 5a. The computation has also led to a good agreement between theoretical and experimental d( 11 B) values for 2a and 2b (max. deviation less than 3 ppm), for individual values see ESI. † The HF/cc-pVTZ calculations of the electrostatic potential (ESP) surface show that the parent 1a has hydridic hydrogen atoms, which can form dihydrogen bonds, 13 the hydridic Bbound hydrogens in 2a and 2b are now replaced by methyl groups of amphiphilic character. 14 The hydrogen atoms of the methyl groups have positive ESP surface and the exo-skeletal carbon atoms have negative ESP surface (see Fig. 5). From the viewpoint of electron transmission, Me groups behave as weak electron acceptors, when compared to toluene, xylene, hexamethylbenzene etc. This is in accord with the 1,6-isomers of the same molecular shape 10 and the same also applies to CMe methyl groups; the lower electron density at C1,10 in 2b in relation to 2a (see C1/C10 body diagonals) may perhaps prove this concept. The electron transmission thus follows the established electronegativity concept (C in CH 3 is more electronegative than C (cage)) reecting the fact that exo-skeletal substituents are bound via classical 2-centre 2-electron bonds. 15 This agrees with the concept elaborated by Viñas et al. on a hexamethylated closo-H 2 C 2 B 10 H 4 Me 6 system. 16 Conceivably, the whole 11 B NMR spectra of 2a and 2b are signicantly paramagnetically deshielded to high frequencies (i.e. downeld shied) with respect to those of parent compounds, for the computed 11 B NMR spectra see ESI. † The constitution of all compounds isolated in this study is also in agreement with the results of multinuclear 11 B, [ 11 B-11 B]-COSY, 17 1 H, and 13 C NMR measurements that led to complete assignments of individual cage BMe, BX, CH, and CMe units (for hardcopies of the NMR measurements, see ESI, Fig. S1-S13 †). The multinuclear ( 11 B, 1 H and 13 C) NMR spectra for all compounds isolated in this work are compared and depicted in Fig. 6, a general feature of the persubstituted compounds being the identity of the 11 B and 11 B-{ 1 H}decoupled NMR spectra that exhibit only singlet resonances.
On the other hand, the 11 B NMR spectrum of the C ssymmetry compound 5a ( Fig. 3 and S12 †) displays 3 : 2 : 2 : 1 patterns of singlets with one coincidental overlap. The 1 H spectrum of 5a ( Fig. 6 and S13 †) shows two different CH signals and four well resolved 2 : 2 : 2 : 1 patterns of BMe resonances in the high-eld; the 13 C-{ 1 H} NMR spectrum contains two different low-eld CH resonances together with a typical low-Scheme 2 Quantitative synthesis of the permethylated derivative closo-1,10-R 2 C 2 B 8 Me 7 -2-OTf.  eld CF 3 quartet, apart from a broad, high-eld BMe signal of intensity 7 (see Fig. S13 †).
The 19 F NMR spectrum of 5a shows one singlet resonance at À76.0 ppm, as expected.

Materials and methods
All the reactions were carried out under argon atmosphere. Dichloromethane and hexane were dried over CaH 2 and freshly distilled before use. Other conventional chemicals were of reagent or analytical grade and were used as purchased. NMR spectroscopy was performed at 400 and 600 Mz (for 1 H), inclusive of standard [ 11 B-11 B]-COSY 17 experiments (all theoretical cross-peaks were observed) leading to complete assignments of    all resonances to individual cage B-vertexes. Chemical shis are given in ppm to high-frequency (low eld) of X ¼ 32.083971 MHz (nominally F 3 B$OEt 2 in CDCl 3 ) for 11 B (quoted AE 0.5 ppm), X ¼ 25.144 MHz for 13 C (quoted AE 0.5 ppm), and X ¼ 100 MHz for 1 H (quoted AE 0.05 ppm), X is dened as in ref. 18 and the solvent resonances were used as internal secondary standards. The starting carboranes of structures 1 and 3 were prepared according to the reported methods. 10,12 Dimethylation of closo-1,10-C 2 B 8 H 10 (1a) on carbon vertices A solution of 1a (120 mg, 1 mmol) in dry Et 2 O (ca. 10-20 ml) was cooled to À78 C and then treated dropwise with 2.5 M LiBu (solution in hexane) (1 ml, 2.5 mmol) under stirring. The offwhite slurry of the Li + salt was stirred for additional 1 h prior to addition of methyl triate (MeOTf, m.w. 164.1) drop by drop, (410 mg, 2.5 mmol) under cooling down in an dry-ice bath. The mixture was then le stirring for additional 2 h at room temperature. Aer adding 5 % hydrochloric acid (10 ml) under repeated cooling and shaking, the Et 2 O layer was separated and evaporated to provide a crude product closo-1,10-Me 2 C 2 B 8 H 8 (1b) in practically a quantitative yield, as assessed by NMR spectroscopy (see Fig. S4-S6 †).

Computational details
Magnetic shielding was calculated using the GIAO-MP2 method incorporated into Gaussian09 (ref. 19) utilizing the IGLO-II basis with the MP2/TZVP geometry and frozen core electrons. Electrostatic potentials were computed at the HF/cc-pVDZ level using Gaussian09 and Molekel4. 3 (ref. 20) programs. It has recently been shown that this basis set size is sufficient for these purposes. 21

X-ray crystallography
The X-ray data for the derivatives 2a and 5a (colourless crystals by slow evaporation of a hexane solution) were collected at 150(2) K with a Bruker D8-Venture diffractometer equipped with Mo (Mo/K a radiation; l ¼ 0.71073 A) microfocus X-ray (ImS) source, photon CMOS detector and Oxford Cryosystems cooling device was used for data collection. The frames were integrated with the Bruker SAINT soware package using a narrow-frame algorithm. Data were corrected for absorption effects using the Multi-Scan method (SADABS). Obtained data were treated by XT-version 2014/5 and SHELXL-2014/7 soware implemented in APEX3 v2016.5-0 (Bruker AXS) system. 22 Hydrogen atoms were mostly localized on a difference Fourier map, however to ensure uniformity of treatment of crystal, all hydrogen were recalculated into idealized positions (riding model) and assigned temperature factors H iso (H) ¼ 1.2U eq (pivot atom) or of 1.5U eq (methyl). H atoms in methyl groups were placed with C-H distances of 0.96 while the hydrogen atoms of the C-H in the carborane cage were assigned according to the maxima on the difference Fourier map.

Conclusions
There are not too many reactions in the area of carborane chemistry that proceed quantitatively. 1 To these rare cases belong syntheses leading to permethylated derivatives of closo-1,10-R 2 C 2 B 8 H 8 (1) reported this work. It was shown that all Bpositions in structures 1 can be furnished with methyl substituents, via electrophilic reactions with MeOTf or MeI reagents.
In quantitative yields proceed also the 1,6-/ 1,10-carbon rearrangement reactions of the isomeric compounds closo-1,6-R 2 C 2 B 8 Me 8 (3). Moreover, the permethylated compounds, such as 2a and 2b, can be, in fact, envisaged as egg (or ellipsoid) shaped hydrocarbons (see Fig. 5) of remarkable air stability due to the protective sheath of the surrounding methyl groups. For example, the persubstituted 2a can be stored in air for at least a month without any noticeable change, while the unprotected 1a is decomposed in air within a couple of hours, especially in a solution. The less stability of the unprotected intermediatesized carborane 1a derives from its non-icosahedral constitution (though it exhibits features of 3D aromaticity 23 ). The quantitative yields and relative easiness of the synthesis predestinate these persubstituted derivatives for using in designed syntheses in specic areas of carborane chemistry as multipurpose reagents, for example in cluster-insertion/ expansion or cage-degradation processes. Apart from this, such compounds are expected to exhibit extreme hydrophobicity, which can be made use of in various directions of chemical or biochemical research. Relevant experiments aimed at extension of permethylation chemistry are therefore in progress in our laboratories.