Icosahedral Meta-Carboranes Containing Exopolyhedral B-Se and B-Te Bonds
Chalcogen-containing carboranes have been known for several decades and possess stable exopolyhedral B(9)-Se and B(9)-Te σ bonds despite the electron-donating ability of the B(9) vertex. While these molecules are known, little has been done to thoroughly evaluate their electrophilic and nucleophilic behavior. Herein, we report an assessment of the electrophilic reactivity of meta-carboranyl selenyl (II), tellurenyl (II), and tellurenyl (IV) chlorides and establish their reactivity pattern with Grignard reagents, alkenes, alkynes, enolates, and electron-rich arenes.These electrophilic reactions afford unique electron-rich B-Y-C (Y = Se, Te) bonding motifs not commonly found before. Furthermore, we show that meta-carboranyl selenolate, and even metacarboranyl tellurolate, can be competent nucleophiles and participate in nucleophilic aromatic substitution reactions. Arene substitution chemistry is shown to be further extended to electronrich species via the palladium mediated cross-coupling chemistry.Crystallographic data are available from the Cambridge Crystallographic Data Centre, under reference numbers CCDC 2105009 (1A), 2105007 (1B), 2105010 (2C), and 2105008 (2D).The following files are available free of charge.Full synthetic procedures, spectroscopic data (PDF).
Introduction<!>Results and Discussion<!>Conclusions
<p>Organoselenium and organotellurium compounds containing carbon-selenium andtellurium bonds have been widely studied for the past decades and have recently found a variety of uses in nearly all aspects of chemical research, including: organic synthesis, 1a-f organometallics, 1g-i self-assembled and applied materials, 1j-n photochemistry, 1o-s and chemical biology. 1t-w In contrast to organochalcogen compounds, the reactivity of boronochalcogens containing boron-selenium and -tellurium bonds are significantly less established. Of currently known molecules containing boron-selenium or -tellurium bonds, a large portion consist of tricoordinate mononuclear boron centers (Figure 1A). 2a-i  Boron sites in these molecules contain a lowest unoccupied molecular orbital (LUMO) capable of accepting some electron density from the bound Se or Te atom, resulting in a shortening of the boron chalcogen bond. Additionally, several examples containing tetracoordinate boron centers 2i-r exist as well (Figure 1B). In these cases, tricoordinate BR 3 (R: C, F, Cl, Br, I, H) are typically stabilized by coordination of chalcogen-based ligands where lone pair electrons on the chalcogen are shared with the vacant boron-centered p-orbital. Lesser known molecular platforms that can support boron-selenium and -tellurium bonding interactions, are boron-rich clusters. 3 Among these, icosahedral carboranes (C 2 B 10 H 12 ) in particular have afforded a unique and stable scaffold for the study of compounds containing boron chalcogen bonds. 4 Similar in size to adamantane, this cluster type exists in three isomeric forms (ortho-, meta-, para-). 5 In all cases, σ electrons responsible for the cluster bonding are delocalized in three dimensions. Given the presence of the carbon vertices and the above delocalization, the resulting asymmetry in the ortho-and metaisomers causes boron vertices most distal from the carbon sites to exhibit strong electron-donating character through induction, similar in magnitude to tertiary alkyl groups. 6 Furthermore, electron delocalization in the cluster results in an inaccessible LUMO, affording B-Y single bond character.</p><p>Carboranes functionalized with exopolyhedral chalcogens (Se, Te) at these electron-rich boron-vertices were first reported in the early 1980's, 4d-f but surprisingly little has been established in terms of understanding the reactivity of these compounds. In previous reports, Zakharkin and coworkers have shown examples of nucleophilic reactivity between caborane-based selenolates or tellurolates with alkyl halides, as well as examples of electrophilic reactivity between carboranebased selenyl (II) reagents and Grignard reagents with no reported electrophilic reactivity of the tellurenyl (II) or tellurenyl (IV) congeners (Figure 1C). 4d-f Notably, the reported compounds have only been characterized by melting point and elemental analysis with no rigorously reported NMR spectroscopy or structural studies. In this work, we report a reactivity map for B(9) functionalized meta-carborane, appended with selenium and tellurium-based functional groups (Figure 2). Specifically, we show that B(9)-bound meta-carboranyl selenyl (II), tellurenyl (II), and tellurenyl (IV) chlorides participate in electrophilic substitution reactions reminiscent to the established reactivity of analogous carbon-based electrophilic chalcogen reagents. 1a Furthermore, we show the ability of B( 9)-bound meta-carboranyl selenolates and tellurolates to participate in nucleophilic aromatic substitution reactions as well as the ability of the corresponding tellurol congener to undergo palladium mediated cross-coupling with an aromatic electrophile. For all compounds, we provide full heteronuclear NMR characterization ( 1 H, 13 C, 11 B, 19 F, 77 Se, and/or 125 Te) in addition to single-crystal X-ray structural characterization for key intermediates studied in this work (Figure 2). Our findings reveal that the electrophilic and nucleophilic reactivity of selenium-and tellurium-containing meta-carboranes is largely analogous to carbon-based reagents.</p><!><p>To ascertain the electrophilic reactivity of these compounds, we first sought to prepare the 9,9'-meta-carboranyl diselenide (1A) and ditelluride (1B) using modified procedures from previous reports (Figure 3A, SI sec. 3). 4d-f,6b Analytically pure dichalcogenides 1A and 1B were isolated via silica gel column chromatography as air stable red-orange and dark red solids, respectively (see SI sec. 3). The isolated dichalcogenides were characterized by heteronuclear NMR spectroscopy ( 1 H, 13 C, 11 B, 77 Se, and/or 125 Te), revealing diagnostic resonances consistent with the proposed structural formulations. 4d-f,6b Single crystals suitable for X-ray crystallography of both dichalcogenides were subsequently grown from layered solutions of dichloromethane and hexanes. The crystallographically derived structures of 1A and 1B further corroborate the presence of exopolyhedral B-Y bonds (1.995 Å (Y=Se, 1A) and 2.215 Å (Y=Te, 1B) in length respectively) located at the B(9) position of metacarborane (Figure 3A). The measured Y-Y dichalcogenide bond lengths and torsional angles, 2.338 Å/96.900 o (Y=Se, 1A) and 2.716 Å/95.694 (Y=Te, 1B) are similar in length to other crystallographically characterized dichalcogenides in addition to torsional angles greater that 90 o being consistent with more sterically hindered dichalcogenides.   The anticipated electrophilicity of 2A prompted us to explore its reactivity with several common nucleophiles. Thus, 2A was treated with an excess of phenylmagnesium bromide in anhydrous diethyl ether at room temperature. After stirring for 16 hours, analysis of the reaction mixture by GC-MS indicated quantitative formation of phenyl selenide (2B). The resulting product was then isolated in 91% yield after purification via silica gel column chromatography and characterized by heteronuclear NMR spectroscopy (Figure 4, SI sec. 5a). Characterization of 2B is in agreement with previously reported data of meta-carboranyl phenyl selenide obtained via an independent chemical route, 8 and confirms the electrophilic behavior of 2A. Considering the successful outcome of the reaction between 2A and a model Grignard reagent, we wanted to assess whether less reactive carbon-based nucleophiles would still undergo transformations with 2A.</p><p>Previously, researchers have established the reactivity of selenyl chlorides with unsaturated hydrocarbons and enolates. 1a As such, norbornene, phenylacetylene, and cycloheptanone were chosen as model compounds potentially susceptible to electrophilic substitution by 2A.</p><p>A solution of 2A in anhydrous dichloromethane was treated with norbornene and the progress of the reaction was monitored by GC-MS. After stirring the mixture overnight, GC-MS indicated the presence of two isomers (2C and 2C', m/z: 352.10, SI sec. 5b,e) approximately in a 1:2 ratio consistent with the anticipated reaction between the electrophilic RSe-Cl fragment in 2A and the C=C in norbornene, forming a distribution of endo and exo isomers. Separation of the two isomers via silica gel column chromatography proved difficult and thus the products were isolated as a mixture in 47% yield and characterized by heteronuclear NMR spectroscopy. While 13 C, 11 B, and 77 Se NMR spectroscopic data of the isomeric mixture provided little insight on the relationship between 2C and 2C', they confirmed the formation of the anticipated selenium-carbon bond as indicated by the upfield shift in the resonances associated with the exopolyhedral boron-selenium bond. 600 MHz and 400 MHz 1 H NMR spectroscopy was used in an attempt to resolve proton resonances in the alkyl region that would correlate to protons bound to the selenium-bound and chlorine-bound carbons of the norbornene (SI sec. 5d). While there was still difficulty resolving 1 H resonances for individual isomers, the presence of more than just two isomers was evident due to their being multiple unique resonances that integrated together as a single proton, in contrast to the isomer distribution observed by GC-MS. To further understand the substitutional isomers present in the purified product, single crystals suitable for X-ray crystallography were grown from a solution of the isomer mixture in dichloromethane layered with hexanes. The crystallographically derived structure indicated the co-crystallization of enantiomeric 2C', revealing the (R,R) and (S,S) exo-products (Figure 4), further confirming the formation of the desired selenium-carbon bond.</p><p>The measured B( 9)-Se and Se-C(1) bond lengths, 1.999 Å and 2.010(R,R)/1.968(S,S) Å respectively, are typical of other crystallographically measured boron-selenium and seleniumcarbon bonds. 9 All characterization of 2C and 2C' suggests the formation of both possible diastereomeric products (endo and exo), resulting from the addition of 2A across the double bond within norbornene in addition to their corresponding enantiomers (R,R and S,S), producing four isomers in total. When subjecting 2A to similar reaction conditions in the presence of phenylacetylene or cycloheptanone, compounds 2D and 2E (SI sec. 5c), were both coincidentally isolated in 54% yield (Figure 4). 1 H NMR spectroscopy of purified 2D revealed the exclusive formation of a single isomer due to presence of only one olefinic 1 H resonance. Single crystals of 2D suitable for X-ray crystallography were then grown from a cold (0 o C) solution of dichloromethane layered with hexanes. The crystallographically derived structure revealed the formation of the E-1-SeR-2-Cl-2-Ph isomer (Figure 4), having resulted from Markovnikov, antiaddition of 2A across the carbon-carbon triple bond in phenylacetylene. The formation of the thermodynamically-favored Markovnikov products from the addition of RSeCl reagents across unsaturated hydrocarbons is expected for this type of process. 1a In contrast to products 2C and 2D, 2E does not incorporate the chloride of the electrophilic reagent, but still forms the expected selenium-carbon bond as indicated by 11 B and 77 Se NMR spectroscopy (Figure 4).</p><p>Beyond reactions of 2A with alkenes, alkynes, and enolates, we also explored its ability to participate in electrophilic aromatic substitution (S E Ar) with toluene. 2A was treated with an excess of anhydrous toluene and aluminum chloride to catalyze the transformation at 50 o C, with the reaction progress monitored by GC-MS. After stirring the mixture overnight, GC-MS indicated the formation of three isomers consistent (Figure 4) with S E Ar occurring between toluene and 2A.</p><p>The crude products were then purified via silica gel column chromatography, affording a mixture of aryl selenide isomers (2F) in 21% isolated yield. In addition to 11 B and 77 Se NMR spectroscopy revealing the formation of the desired aryl selenide, 1 H NMR spectroscopy also indicates the para tolyl isomer as the major component in the isomeric mixture (SI sec. 5c), consistent for S E Ar mechanisms with toluene. Resolving all three isomers by 1 H NMR spectroscopy proved to be quite difficult not only due to the low abundance of the ortho-and meta-isomers, but also the prevalence of 1 H resonances attributed to the carborane B-H vertices in the alkyl region. In order to deconvolute the 1 H NMR and obtain a more accurate ratio of isomer, the S E Ar between 2A and toluene was repeated with perdeuterated toluene (SI sec. 5e). 2 H NMR spectroscopy of the isolated product clearly revealed the distribution (para:ortho/meta) of isomers to be 89:11, in agreement with the distribution determined by GC-MS. With the electrophilicity of 2A established, we chose next to explore that of 3A. First, the reaction of 3A with phenylmagnesium bromide was assessed to confirm the electrophilic character of 3A. After addition of the Grignard reagent to form the desired phenyl telluride (3B), the product was isolated via silica gel column chromatography in 75% yield (SI sec. 6a). Importantly, the NMR characterization of 3B agrees with previously reported characterization by our group of metacarboranyl phenyltelluride obtained via an independent chemical route (Figure 5A). 8 We then attempted the reaction of 3A with phenylacetylene to determine its ability to react with unsaturated hydrocarbons. 3A was suspended in anhydrous dichloromethane before the addition of phenylacetylene. After stirring the suspension at room temperature for 16 hours, 11 B NMR spectroscopy of the reaction mixture revealed only the presence of 3A and 1B as a decomposition product (Figure 5A, see SI sec. 6b). In an attempt to improve conversion to the desired telluride, the reaction was attempted in chloroform at reflux temperature. However, after stirring the reaction mixture for 8 hours, conversion to the desired telluride was lower than anticipated (see SI sec 6c) and contained significant quantities of starting material (3A) and 1B as indicated by 11 B NMR spectroscopy. We attribute this general decrease in reactivity to a combination of both the inherently lower electronegativity of tellurium and the electron donating ability of meta-carborane at the B(9) position, 6 resulting in the diminished electrophilicity of 3A. To test our hypothesis, we attempted the reaction between 4A and phenylacetylene in refluxing chloroform. In contrast to the selectivity of organic selenyl (II) chlorides and 2A to form products with unsaturated hydrocarbons resulting from Markovnikov anti-addition, the preferred substitution mechanisms of organic tellurenyl (IV) trichlorides are much more difficult to predict, possibly due to the formation of four-centered intermediates (Markovnikov, syn in nonpolar solvents), three-centered intermediates (Markovnikov, anti), or radical-based intermediates. 1a,10 Notably, the reactions of tellurenyl (IV) trichlorides with phenylacetylene have typically afforded Markovnikov syn-addition products, consistent with the in situ formation of a four-centered intermediate, and selectivity for syn over anti-addition predicated on the polarity of solvent used for the reaction medium. To assess the reactivity of 4A, it was first suspended in chloroform followed by the addition of phenylacetylene.</p><p>After stirring the white suspension for 6 hours at reflux (65 o C), a clear, yellow solution remained (SI sec. 7a). In situ 11 B NMR spectroscopy of the reaction mixture revealed full consumption of 4A and a diagnostic upfield shift in the resonance attributed to the exopolyhedral boron-tellurium bond (Figure 5B). This change in resonance chemical shift is consistent with the presence of the key dichlorotelluride intermediate (4B*), and suggests the formation of the desired telluriumcarbon bond. However, in contrast to the formation of the selenium-containing congener (2D), in situ 125 Te NMR spectroscopy revealed the presence of two tellurium-containing isomers with similar chemical shifts approximately in a 2:1 ratio, attributed to 4B* and 4B*' Z/E isomers. To further understand the reaction mechanism being employed by 4A in the reaction with phenylacetylene, a series of control reactions were performed to rule out the possible intermediates previously shown to be accessible with tellurenyl (IV) trichlorides vide supra (see SI sec. 7b,c) 1a,10 and probed via in situ 125 Te NMR spectroscopy. When the reaction was performed in the presence of a radical inhibitor, no significant change in the distribution of 4B* and 4B*' was observed, likely ruling out the possibility of a radical-mediated substitution mechanism. However, when the reaction was performed in toluene, a relatively non-polar solvent, 4B* was formed exclusively with no measurable amount of 4B*' by 125 Te NMR. This selectivity, as influenced by solvent polarity, is reminiscent to the behavior of four-centered tellurenyl (IV) trichloride intermediates, resulting in selective Markovnikov syn addition (4B*) of 4A to phenylacetylene when conducting the reaction in toluene and a mixture of four-centered and three-centered tellurenyl (IV) trichloride intermediates forming syn (4B*) and anti-addition (4B*') products when in chloroform. The isomeric mixture of 4B* and 4B*' was then reduced to the desired telluride (4B and 4B') by treatment with an aqueous solution of sodium thiosulfate and the progress of the reduction was monitored by TLC. Once the reduction was complete, 4B and 4B' were isolated from the crude reaction mixture via silica gel column chromatography as a mixture of Z/E isomers in 70% yield and characterized by heteronuclear NMR spectroscopy to confirm the formation of the desired tellurium-carbon bond. 1 H and 125 Te NMR spectroscopy revealed the isolation of two distinct isomers, 4B and 4B' in approximately a 2:1 ratio (Figure 5B, SI sec. 7a). Two broad quartet resonances in the 1 H aromatic region (7.45 and 7.07 ppm) are attributed to the olefinic 1 H's and are used to determine the isomer distribution. Furthermore, 125 Te NMR spectroscopy revealed two 125 Te resonances at -10 and -15 ppm, with approximate relative intensities of 1:2, respectively, and agrees with the distribution observed by 1 H NMR (Figure 5B, see SI sec. 7a). This additional isomer is likely attributed to the formation of E-1-TeR-2-Ph-2-Cl (R: meta-carboranyl) as the minor product that was enabled by the increased polarity of the reaction solvent. This minor product is produced from a portion of 4A reacting with phenylacetylene through a three-centered intermediate, similar to the substitution mechanism employed by 2A.</p><p>In summary, the assessment of electrophilic behavior for meta-carboranyl selenyl (II), tellurenyl (II), and tellurenyl (IV) chlorides reveal that their reactivity is reminiscent to carbonbased reagents. 2A reacts with Grignard reagents, alkenes, alkynes, enolates, and electron-rich aromatics to form products that would generally be expected for organic selenyl chlorides. Despite, the electron-donating ability of the B(9) position to which the selenyl (II) chloride in 2A is appended to, no deleterious effects to the overall electrophilic reactivity of 2A are observed. In contrast, the electrophilic reactivity of the tellurenyl (II) chloride 3A is significantly dampened, only showing good reactivity with Grignard reagents. To enhance the electrophilic reactivity, the tellurenyl (IV) chloride 4A was studied. An increase in oxidation state at tellurium significantly enhanced the electrophilic reactivity and reacts more readily with terminal alkynes. The regioselectivity and stereoselectivity behavior of 4A when reacting with terminal alkynes in various solvents closely parallels the behavior of organic tellurenyl (IV) chlorides, forming either the syn or anti-addition products as a function of solvent polarity.</p><p>With the electrophilicity of 2A, 3A, and 4A established, we proceeded to expand the nucleophilic substitution chemistry available with selenium and tellurium-containing metacarboranes. The ability of meta-carborane-based selenolates and tellurolates to participate in S N 2 substitution mechanisms with alkyl halides is well established. 4d,f However, their ability to participate in S N Ar substitution mechanisms is not known. To further understand the nucleophilic behavior of boron-bound selenium and tellurium-containing carboranes, we prepared the 9-metacarboranyl selenol (5A) and tellurol (6A). We envisioned that these compounds, upon deprotonation, would act as precursors to the corresponding nucleophilic chalcogenolates. Selenol (5A), was synthesized according to previously reported methods and its spectroscopic characterization is in agreement to the proposed formulation (SI sec. 8a). 4d,6b While the boronbound tellurol (6A) has not been reported previously, we were able to successfully synthesize 6A using modified reduction procedures (SI sec. 9a). 6A is isolated in 67% yield as a colorless, odorless, air sensitive solid that nevertheless can be handled in air for short periods of time (~10 minutes) without significant decomposition. In contrast to all other known carborane chalcogenols, 6A is light sensitive and reverts to the ditelluride (1B) when exposed to ambient light, even when stored in a nitrogen-filled glovebox. The 1 H and 125 Te resonances measured by NMR spectroscopy, -7.15 ppm and -596.5 ppm respectively, are indicative of the exceedingly electron-rich environment experienced by the tellurol from the B( 9) meta-carboranyl susbstituent and are consistent with other reported sterically hindered electron-rich tellurols. 11 This is the first reported synthesis of an isolable carboranyl tellurol, and is a rare example of an isolable tellurol. The compound was subsequently purified from the crude reaction mixture via silica gel column chromatography in 61% isolated yield and characterized by NMR spectroscopy. 19 F NMR revealed a diagnostic resonance pattern consistent with mono-substituted perfluorotoluene in the paraposition and is in agreement with the proposed structure formulation. Furthermore, 77 Se NMR showed a downfield shift in the resonance attributed to the exopolyhedral boron-selenium bond found in 5B, and is consistent with the formation of an aryl selenide (Figure 6A). S N Ar was then attempted with the tellurol (6A) using similar conditions, though taking additional precautions to limit exposure to light and oxygen (SI sec. 9b). Following similar isolation procedures to 5B, the desired aryl telluride (6B) was isolated in small yield (13%), sufficient for full characterization by NMR spectroscopy. Due to the general instability of the in situ generated tellurolate under the reaction conditions, ditelluride (1B) was a major byproduct formed during the reaction between 6A and perfluorotoluene (SI sec. 9d).</p><p>To study the reactivity of 6A further with more electron-rich aryl-based electrophiles, we attempted arylation with a stochiometric palladium-based oxidative addition complex. These oxidative addition complexes are typically used stoichiometrically for the arylation of sensitive substrates due to their high degree of selectivity for chalcogenols and ease of preparation. 12 A solution of 6A in dichloromethane was prepared in a dark, nitrogen filled glovebox without the addition of base to avoid incompatibilities of the tellurolate with the oxidative addition complex (SI sec. 9c). Subsequently, [4-tolyl-PdRuPhos][OTf] (Figure 6B) was added and the reaction progress was monitored by GC-MS. After 30 minutes, GC-MS indicated the formation of a compound with an m/z of 363.20, suggesting the formation of the desired tolyl telluride (6C). 6C was isolated from the crude reaction mixture via silica gel column chromatography in 56% yield and characterized by NMR spectroscopy. 125 Te NMR revealed a resonance with a chemical shift of 46.5 ppm, similar to that of 3A (Figure 5, 6B). Overall, these studies indicate that B(9) metacarboranyl selenolate and tellurolate can be competent nucleophiles and are able to participate in S N Ar and Pd-mediated arylation processes, leading to the formation of selenoether and telluroether moieties with B-Y-C connectivity.</p><!><p>In conclusion, B( 9)-connected meta-carboranyl selenyl and tellurenyl reagents have been shown to participate in electrophilic substitution reactions with unsaturated hydrocarbons, including alkenes, alkynes, enolates, and aromatic substrates; reminiscent to other electrophilic organochalcogen compounds. We further show the first examples of nucleophilic aromatic substitution with carborane selenolates and tellurolates as well as the first use of palladium-based oxidative addition complexes for the arylation of a free tellurol. All formed products contained the unique B-Se-C or B-Te-C bonding motifs and are stable in air despite the exceedingly electronrich environment experienced by either the selenium or tellurium nucleus as suggested by the 77 Se and 125 Te NMR spectroscopic experiments. The reactivity map developed in this work serves as an expansion of available modification reactions for carboranes and other polyhedral boron clusters containing C-or B-connected exopolyhedral heteroatom substituents, 13 as well as benchmarks similarities and differences in terms of reactivity and stability with the fundamental chemistry of electron-rich chalcogen-containing molecules. 1a,10,11,14 Synthesis of unsymmetrical B 2 E 2 and B 2 E 3 heterocycles by borylene insertion into boradichalcogeniranes. Chem. Sci. 2019, 10, 4662-4666. (j) Liu, S.; Légaré, M.-A.; Hofmann, A.; Braunschweig, H. A Boradiselenirane and a Boraditellurirane: Isolable Heavy Analogs of Dioxiranes and Dithiiranes. J. Am. Chem. Soc. 2018, 140, 36, 11223-11226. (k)</p>