1 Kizshura

Carborane Synthesis Essay

Conspectus

Carboranes are a class of polyhedral boron hydride clusters in which one or more of the BH vertices are replaced by CH units. Their chemistry has been dominated by vertex carboranes for over half a century. In contrast, knowledge regarding supercarboranes (carboranes with more than 12 vertices) had been limited merely to possible cage geometries predicted by theoretical work before Only in recent years has significant progress been made in synthesizing supercarboranes. Such a breakthrough relied on the use of Carbon-Atoms-Adjacent (CAd) nido-carborane dianions or arachno-carborane tetraanions as starting materials. In this Account, we describe our work on constructing and elucidating the chemistry of supercarboranes.

Earlier attempted insertions of the formal [BR]2+ unit into Carbon-Atoms-Apart (CAp) vertex nido-[7,9-C2B10H12]2– did not produce the desired vertex carboranes. Such failure is often attributed to the extraordinary stability of the B12 icosahedron (the “icosahedral barrier”). However, the difference in reducing power between CAp and CAd vertex nido-carborane dianions had been overlooked. Our results have shown that CAd nido-carborane dianions are weaker reducing agents than the CAp isomers, allowing a capitation to prevail over a redox reactivity. This finding provides an entry point to the synthesis of supercarboranes and a series of and vertex closo-carboranes have been prepared and structurally characterized. They share some chemical properties with those of vertex carboranes; on the other hand, they have their own unique characteristics. For example, a vertex closo-carborane can undergo single electron reduction to give a stable carborane radical anion with [2n + 3] framework electrons, which can accept one additional electron to form a vertex CAd nido-carborane dianion. Vertex closo-carborane can also react with various nucleophiles to afford the cage carbon and/or boron extrusion products closo-CB11, nido-CB10, closo-CB10, and closo-C2B10, depending on the nature of the nucleophiles.

Studies of supercarboranes remain a relative young research area, particularly in comparison to the rich literature of icosahedral carboranes with vertices. Other supercarboranes are expected to be prepared and structurally characterized as the field progresses, and the results detailed here will further these efforts.

1. Introduction

The icosahedral closo carboranes (dicarba-closo-dodecaboranes; C2B10H12) are an interesting class of exceptionally stable boron-rich clusters with high thermal and chemical stability, hydrophobicity and acceptor character [1,2,3]. Carborane chemistry has experienced a major surge of interest across a wide spectrum of technologies, fueled by developing applications in diverse areas such as in catalysis, materials science and medicine [1,4,5,6,7,8,9,10,11]. There are three isomers of carborane that differ in the relative position of both carbon atoms in the clusters (ortho-, meta- and para-, or o-, m- and p-; Figure 1). Although the volume of the three isomers of carborane is roughly the same, they show very different dipole moments as a consequence of the different arrangement of the carbon atoms in the cluster ( D, D and zero D for o-, m- and p-, respectively) [8]. The average size of the three isomers of carborane (– Å3) is comparable to that of adamantane ( Å3), significantly larger (40%) than the phenyl ring rotation envelope ( Å3) and slightly smaller (10%) than C60 ( Å3) [12]. The presence of ten hydridic hydrogens at the boron atoms of the clusters makes them extremely hydrophobic, surpassing that for adamantane [13]. The hydrophobicity of carboranes has been extensively used to trigger desired biological actions [7,8]. Concerning the electronic effect, all cluster carbon atoms exert an electron-withdrawing effect on attached substituents, which decreases in the order o- to m- to p-carborane. For example, when bonded by a cluster carbon atom, o-carborane exhibits an electron-withdrawing substituent effect similar to that of a fluorinated aryl group. Experimental evidence shows that the electron-withdrawing character of the carborane isomers has a clear impact on the acidity of substituents at carbon, the acidity decreasing in the same order (o-, m-, p-), and all being more acidic than the related phenyl moiety [3]. Thus, the C–H bonds of the icosahedral closo carboranes can be deprotonated with strong bases (e.g., alkyllithium) and the generated carboranyl nucleophile can react with a wide variety of electrophiles (e.g., alkylhalides, carbonyl derivatives, etc.) producing C–functionalized carboranes. Monosubstitution of the carboranes is not trivial because the monolithiation of the o-carborane moiety is complicated by the tendency of the monolithio o-carborane to disproportionate into o-carborane and its dianion [14]. Several strategies have been followed to overcome this problem, for example, by using protecting/deprotecting methodologies, using dimethoxyethane as the solvent, or by doing the reaction at high dilution [15,16]. We recently revealed that mono and disubstitution of carboranes can be conveniently done in ethereal solvents at a very low temperature [17]. Such nucleophilic substitution methodology is perhaps the more general route for functionalizing carboranes as it can be applied to all carborane isomers.

Over the years, our group and others have been interested in the synthesis of new carborane-based ligands containing a variety of donor centers (N, P, S, N/C, N/S, N/P, P/C, P/P P/Si, P/S, S/C or S/S donors) and their metal complexes an applications [2,6,18,19,20,21,22,23,24,25,26,27,28]. Carborane ligands containing N,O donors are scarce in the literature. This is somewhat surprising when considering the importance of classical N,O-ligands in metal complexes and their properties [29,30,31,32,33,34]. One of the main objectives of our research in the last few years was to study the chemistry of carboranylmethylalcohols, particularly of those containing a heteroatom such as nitrogen, and exploring their properties. Our interest in N/O-functionalized carboranes primarily stems from our rationale that introducing a carborane moiety in the place of a conventional carbon-based moiety would strongly influence the coordination chemistry of such compounds, in addition to other relevant properties, such as higher stability, hydrophobicity, etc. Integration of carboranes in place of organic ring systems (typically benzene) is a very popular strategy to trigger desirable properties in (bio)medicine [7,8] but is much less exploited in chemistry or materials science [35].

In the present review, we summarize our results and the results of others on the synthesis, structure and reactivity of carboranyl ligands containing N,O-donor atoms and their metal complexes and properties. Metallacarborane complexes, incorporating one or more metal atoms within a polyhedral carborane cage structure, are excluded of the present review. For some recent reviews on metallacarboranes see references [36,37,38,39,40,41].

2. Carboranyl Compounds with N,O-Donor Functionalities and Properties

Closo-Carboranylmethylalcohols with Nitrogenated Aromatic Rings

Reported pyridine-type containing carboranyl-based N,O-donor compounds are summarized in Chart 1. Carboranyl methanols are easily available by the addition of lithiocarboranes to aldehydes or ketones. Using this methodology, a wide variety of mono substituted carboranyl methanol derivatives have been synthesized [42,43]. Following a similar procedure we [44,45,46,47,48,49] and others [50,51] have prepared an extensive series of new monosubstituted o-, m- and p-carboranylmethylalcohols bearing nitrogenated aromatic rings, by the addition of lithiocarboranes to the corresponding pyridylaldehydes (14, Chart 1 and Scheme 1). The addition of dilithiocarboranes to two equivalents of the corresponding aldehydes, under the same reaction conditions, provided a new series of disubstituted o- and m-carboranylmethylalcohols (56, Chart 1) [52,53]. This synthetic methodology allows the preparation of the compounds in good yields in gram quantities from one-pot reactions, starting from commercially available materials.

This family of carboranylmethylalcohols contains one (14; Chart 1) or two (56; Chart 1) chiral carbon centers. The monosubstituted compounds are therefore obtained as racemic mixtures, and they can be easily resolved into the R and S enantiomers by using HPLC over a chiral stationary phase [49,54], or by diastereomers formation with (1S)-(−)-camphanic acid chloride [50,51]. In the case of the disubstituted compounds (56), the situation is more complex (Scheme 2). These compounds contain two chiral centers that can adopt either R or S configuration and, therefore, lead to the formation of two diastereoisomers (Scheme 2), a meso compound (RS; OH groups in a syn orientation) and a racemic compound (mixture of SS and RR; OH groups in an anti orientation). The enantiopure compounds can be exploited in coordination chemistry, as will be described in the following sections. Separation of the syn- and anti-isomers in the disubstituted series of compounds has been carried out in the case of o-carborane derivatives 5a and 5b [53,55].

Both mono and disubstituted carboranylmethylalcohols mentioned above possess hydroxyl (OH) groups as hydrogen bond donors and nitrogen atoms that act as hydrogen bond acceptors. Indeed, the supramolecular chemistry of such compounds is dominated by moderate O–H∙∙∙N hydrogen bonding. In the case of 2-pyridyl derivatives, 2a, 3a and 4b (both in racemic and enantiopure forms), they all form homochiral helical networks and it has been shown that a correlation exists between the OCCN torsion angles of the molecules in the solid state and the handedness of the supramolecular helices [49]. Regarding the disubstituted derivatives, 5af, it was observed that syn and anti stereoisomers crystallized separately from their mixtures and the detailed analysis of their supramolecular structures revealed that homochiral recognition seems to operate also in these molecular systems [53].

Other Closo-Carboranes Incorporating N and O Functionalities

Other reported non pyridine-type containing carboranyl-based N,O-donor compounds are summarized in Chart 2. A related family of compounds to that of 14 and 6 (Chart 1) is that of chiral carboranylpyrroles 711 (Chart 2) [56]. In these molecules, the pyridyl moieties in the former ones are replaced by a pyrrol moiety. These carboranylpyrroles were prepared by the reactions of mono or dialdehydes derivatives of o-, m- and p-carborane with pyrroles in the presence of acid catalysts (Scheme 3). Provided that the pyrrol moieties could be deprotonated, these compounds might provide rich coordination chemistry.

Reaction of o-carboranylmethyl ammonium salt with commercially available phenyl aldehyde provided the phenyl(carboranylmethyl)imine 12 (Chart 2 and Scheme 3) in good yield [57]. Another interesting series of compounds is that of chiral bis(oxazolilnyl)-m-carboranes 1314 that were synthesized via a multistep synthesis [58]. Briefly, m-carborane dicarboxylic acid was transformed to the acyl chloride with SOCl2 and further condensed with two equivalents of the corresponding resolved amino alcohols to provide the uncycled bis(hydroxyamide)-m-carborane intermediates. Double cyclization reaction by diethylaminosulfur trifluoride (DAST) afforded enantiopure compounds 1314 in very high yields (Scheme 3).

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