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. Author manuscript; available in PMC: 2021 Mar 26.
Published in final edited form as: Org Process Res Dev. 2019 Aug 5;23(8):1638–1645. doi: 10.1021/acs.oprd.9b00257

Off-Cycle Processes in Pd-Catalyzed Cross-Coupling of Carboranes

Rafal M Dziedzic †, Jonathan C Axtell †, Arnold L Rheingold ‡, Alexander M Spokoyny †,§
PMCID: PMC7996392  NIHMSID: NIHMS1584536  PMID: 33776400

Abstract

Off-cycle processes in catalytic reactions can dramatically influence the outcome of the chemical transformation and affect its yield, selectivity, rate, and product distribution. While the generation of off-cycle intermediates can complicate reaction coordinate analyses or hamper catalytic efficiency, the generation of such species may also open new routes to unique chemical products. Recently, we reported the Pd-mediated functionalization of carboranes with a range of O-, N-, and C-based nucleophiles. By utilizing a Pd-based catalytic system supported by a biaryl phosphine ligand developed by Buchwald and co-workers, we discovered an off-cycle isomerization process (“cage-walking”) that generates four regioisomeric products from a single halogenated boron cluster isomer. Here we describe how several off-cycle processes affect the regioisomer yield and distribution during Pd-catalyzed tandem cage-walking/cross-coupling. In particular, tuning the transmetallation step in the catalytic cycle allowed us to incorporate the cage-walking process into Pd-catalyzed cross-coupling of sterically unencumbered substrates, including cyanide. This work demonstrates the feasibility of using tandem cage-walking/cross-coupling as a unique low-temperature method for producing regioisomers of mono-substituted carboranes.

Keywords: Off-cycle, Catalysis, Carboranes, Cage-Walking, Deboronation

Introduction

Since the discovery of metal-catalyzed cross-coupling, researchers have observed off-cycle processes in the manipulation of hydrocarbon-based molecules (e.g. metal-mediated β-hydride elimination and chain-walking).1–3 While off-cycle processes may lead to catalytically inactive by-products that hamper the efficiency of catalytic cycles,4,5 understanding these off-cycle processes is critical to improving reaction selectivity and suppressing detrimental reaction pathways. Off-cycle processes in metal-catalyzed reactions can have utility as alternate reaction pathways that enable new or non-intuitive reactivity in synthesis.6–12

An appealing aspect of off-cycle processes is the isomerization of a substrate molecule into regioisomers that cannot be easily synthesized.13 Such isomerization reactions are particularly useful when studying structure-activity relationships among isomers because these reactions can help identify lead compounds from a single reactant.14

We and others have recently been expanding the application of Pd-based cross-coupling methodology to 3-dimensional icosahedral carborane substrates.15–27 These compounds possess several unique spectroscopic features such as NMR active 11B/10B, IR and Raman active B-H bond stretching modes, and distinct 11B-10B isotopic patterns in mass spectrometry enable detection of icosahedral boranes by a variety of analytical methods.28–31 In particular, the three isomers (ortho-, meta-, and para-) of dicarba-closo-dodecaboranes (o-/m-/p-C2B10H12) are of interest due to their commercial availability and their utility as 3D scaffolds in molecular design. The ortho- and meta-C2B10H12 isomers each have a pronounced dipole moment, four sets of chemically inequivalent B-H vertices, and one set of chemically equivalent C-H vertices. The variety of substituted regioisomers available to carboranes allows them to act as electronically distinct, isosteric functional groups (Figure 1). The electronic diversity among carborane regioisomers has enabled the tuning of their hydrophobicity, pharmacological properties, photoluminescence, and surface chemistry.32

Figure 1.

Figure 1.

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Electrostatic potential map of m-carborane and adamantane. Molecular volume based on Connolly solvent excluded volume using a 1.4 Å probe sphere (see SI for computational details).

Among the presently available boron vertex functionalization methods, metal-catalyzed transformations enable the installation of the broadest class of chemical groups. These metal-catalyzed methods can be loosely grouped into 1) directed B-H activation and 2) cross-coupling at B-X bonds (X = Br or I).33–35 While B-H activation methods often target the electron deficient B-H vertices (those closest to the carbon vertices),36,37 cross-coupling at B-X bonds can occur at electron-rich and electron-poor boron vertices.38 Thus, direct and selective synthesis of halo-carborane regioisomers is the main challenge to synthesizing the corresponding regioisomeric carborane product via metal-catalyzed cross-coupling. The two strategies are reminiscent to methods used for the functionalization of aromatic and heteroaromatic hydrocarbon congeners and are complementary in their nature. However, despite the prevalence of metal-catalyzed isomerization chemistry for hydrocarbon molecules, the methodology for accessing all four boron-substituted regioisomers for icosahedral carboranes is still fundamentally underexplored.

In the case of meta-carborane (mCB), facile electrophilic halogenation occurs at the electron-rich B(9)-H vertex to produce 9-Br-m-carborane (Br-B(9)). However, synthesis of the other regioisomers (5-Br-m-carborane, Br-B(5); 4-Br-mcarborane, Br-B(4); and 2-Br-m-carborane, Br-B(2)) is more challenging. For example, deboronation and halogenation followed by boron vertex reinsertion enable synthesis of the B(2) regioisomer.39,40 Alternatively, thermal isomerization of Br-B(9) occurs at temperatures >300 °C and produces a statistical distribution of 9/5/4/2-bromo-m-carborane (Br-mCB) isomers.41–44 The thermal isomerization process is one of the few methods to synthesize Br-B(5) and Br-B(4). The difficulty associated with synthesizing these mCB regioisomers is perceived as a significant obstacle to the study of carborane-based molecules and their regioisomers.

Recently, we reported the discovery of an off-cycle Br-mCB isomerization process (“cage-walking”) that bypasses the need to synthesize the B(9/5/4/2) Br-mCB regioisomers for subsequent cross-coupling to form B(9/5/4/2)-functionalized mCB regioisomers.45 The cage-walking process isomerizes the Br-B(9) substrate into all four Br-mCB regioisomers (Figure 2). This tandem cage-walking/cross-coupling process allows Br-B(9) to serve as a precursor to B(9/5/4/2) substituted mCB. The selectivity for cross-coupling at the B(5/4/2) vertices appears to be driven by the increased electrophilicity of the Pd(II) center when the carborane is bound through the more electron-poor (B(2) > B(4) > B(5)) boron vertices.45 However, so far the utility of the tandem cage-walking/cross-coupling process has been limited to sterically hindered nucleophiles. Thus, we set out to 1) understand the reaction conditions necessary to access the cage-walking process and 2) identify methods for controlling the cross-coupling of sterically unencumbered nucleophiles.

Figure 2.

Figure 2.

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Proposed tandem cage-walking/cross-coupling cycle. The red box encapsulates the cage-walking process and the blue box encapsulates the cross-coupling process. Deleterious off-cycle pathways are shown on the right side of the tandem cage-walking/cross- coupling, inset shows the single crystal X-ray diffraction crystal structure of [XPhosPd(nido-CB)]. Steps: i. Oxidative addition, ii. cage-walking, iii. transmetallation, iv. reductive elimination, v. deboronation of Nu-B(2) by base, vi. aggregation of palladium into palladium particles, vii. ligation of [XPhosPd] by nido-CB.

Cage-Walking Isomerization by [LPd]

In order to integrate the cage-walking process in various Pd-catalyzed cross-coupling reactions, we set out to identify the reaction components that facilitate Pd-catalyzed Br-B(9) isomerization. In our previous studies we used an [XPhos-Pd-G3] precatalyst to generate the active [XPhosPd] catalytic species. This method required the use of an exogenous base to deprotonate the precatalyst which produces the [XPhosPd] by reductive elimination of a carbazole molecule.46 To evaluate whether cage-walking occurs in the absence of precatalyst by-products, we prepared the [XPhosPd] catalyst by using [Pd(cod)(CH2Si(CH3)3)2] (cod = 1,5-cyclooctadiene) as an alternative Pd0 source in the presence of dialkyl biaryl phosphine ligands.47 Similar to the [XPhos-Pd-G3] precatalyst system, we observed cage-walking when Br-B(9) was treated with a solution of [XPhosPd] at 80 °C (Figure 3), suggesting that the cage-walking process is independent of the presence of base and likely undergoes a unimolecular isomerization. Since there is no oxidant in the reaction mixture strong enough to facilitate a Pd(II)/Pd(IV) cycle, we believe that the cage walking process likely does not involve a Pd(IV) intermediate (see SI Figure S12 for proposed cage-walking mechanisms). Examination of other dialkyl biaryl phosphine ligands (RuPhos, L2, CyJohnPhos, L3) revealed that the cage-walking process is not exclusive to the XPhos ligand. However, the total isomer yield is highest when using the XPhos (L1) ligand. Notably, we did not observe cage-walking isomerization of 9-I-m-carborane in the presence of 5 mol% [XPhos-Pd-G3] precatalyst with K3PO4 in 1,4-dioxane at 80 °C.

Figure 3.

Figure 3.

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GC-MS yields of Br-mCB regioisomers produced by Pd- catalyzed cage-walking starting with Br-B(9).

Next, we examined whether certain additives could affect the amount of Br-mCB isomers formed during cage-walking (Figure 3). We found that presence of Lewis bases or excess bromide reduces the relative ratios of cage-walked Br-mCB isomers. For example, addition of 4-dimethylaminopyridine, DMAP, or (nBu4N)Br reduced the amount of B(2/4/5) Br-mCB isomers from 21% to 10% and 1%, respectively. These observations would be consistent with a catalytically relevant intermediate ([XPhosPd(mCB)]+) for the cage-walking process in which the formally cationic Pd-center bears a vacant coordination site. In order to probe this mechanistic hypothesis further, we focused on additives that might promote Pd-Br bond cleavage in [XPhosPd(mCB)Br] to yield a [XPhosPd(mCB)]+ species with a vacant coordination site that we suspect is responsible for the activation of an adjacent B-H bond and subsequent cage-walking. Importantly, the sum of B(2/4/5) Br-mCB isomers can be increased from 20% to 26% by addition of Ca(OH)2 to the cage-walking reaction. This increase in Br-mCB isomers is attributed to the ability of layered hydroxides to intercalate anions and form OH···Br interactions that may promote formation of [XPhosPd(mCB)]+.48 We also found that the identity of the base (including those soluble in organic media, e. g. trimethylamine) had little effect on Br-B(9) isomerization, and only one equivalent of base (relative to [XPhos-Pd-G3] precatalyst) was needed to form the [XPhosPd] complex. This set of experiments demonstrates how certain additives or reaction by-products can affect the cage-walking process and the overall distribution of mCB regioisomers.

Tandem Cage-Walking/Suzuki-Miyaura Coupling

In our initial study of tandem cage-walking/cross-coupling with phenols, we observed that a combination of a sterically encumbered biaryl phosphine ligand and a sterically encumbered substrate generate a higher percentage of B(2) regioisomers than their less hindered counterparts. For example, under otherwise identical conditions, tandem cage-walking/cross-coupling of 3,5-dimethylphenol with Br-B(9) gave 30% of B(2)-substituted mCB whereas the bulkier but electronically comparable 2,6-trimethylphenol gave 76% B(2)-substituted mCB.45 This pronounced selectivity for cage-walking was attributed to the substrate control engendered by the sterics of the phenol moiety that can modulate the rate of transmetallation. We hypothesized that such steric control may not be necessary in the case of other substrates such as arylboronic acids, where the electronic properties of the aryl substituent can dictate the rate of transmetallation. For example, the tandem cage-walking/Suzuki-Miyaura coupling of p-tolylboronic acid with Br-B(9) produced the p-tolyl-B(2) isomer as the major product. This suggests that certain transmetallating agents can mitigate the nucleophilicity of the cross-coupling partner and allow the relative rates of cage-walking and transmetallation to be competitive with each other.

We surveyed the steric and electronic effects of –F and – OCH3 substituents on the efficacy of tandem cage-walking/Suzuki-Miyaura cross-coupling. Generally, we found that electron-rich arylboronic acids (p-/m-/o-)-CH3Ophenylboronic acid) produced more B-Aryl-m-carborane (Aryl-mCB) than the electron-poor arylboronic acids (p-/m-/o-F-phenylboronic acid) (Figure 4). The presence of an ortho-substituent appears to have an inhibitory effect on the cross-coupling of o-OCH3-phenylboronic acid but has a beneficial effect for o-F-phenylboronic acid. Although both functional groups are ortho-directing, the increased steric bulk of the -OCH3 group near the nucleophilic site may inhibit transmetallation and lead to less Aryl-mCB formation. Conversely, electron-poor arylboronic acids resulted in lower Aryl-mCB yields and more by-product formation, vide infra. These differences in Aryl-mCB yield may be due to reduced nucleophilicity of the arylboronic acid which would make transmetallation of the aryl moiety more difficult. Additionally, arylboronic acids bearing Lewis basic groups such as 4-CN-phenylboronic acid and 3-pyridylboronic acid did not result in cross-coupling. The presence of Lewis acidic groups in 4-CN-phenylboronic acid and 3-pyridylboronic acid can suppress the cage-walking process which may prevent formation of the more electrophilic B(2)-bound [XPhosPd(mCB)]+ catalyst species.49

Figure 4.

Figure 4.

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GC-MS yields of carborane containing species produced during tandem cage-walking/Suzuki-Miyaura cross-coupling.

In addition to formation of Aryl-mCB, we also observed formation B-OH-m-carborane regioisomers (OH-mCB) and BF-m-carborane (F-mCB) as a by-product of the tandem cage-walking/cross-coupling (Figure 4). While the formation of OH-mCB was observed previously by us and others,26,50 and is likely due to the presence of adventitious moisture in the system, formation of F-mCB by cross-coupling of nucleophilic fluoride is rare.27 Neither of these by-products are surprising given the larger thermodynamic driving force for the formation of B-O and B-F bonds relative to C-O and C-F bonds.51 This contrasts with Suzuki-Miyaura cross-coupling reactions where off-cycle C-O and C-F bond formation is rarely observed even in aqueous reaction conditions. Notably, the arylboronic acids with electron withdrawing groups resulted in more OH-mCB than the electron-rich arylboronic acids. The formation of OH-mCB may be due to transmetallation of the hydroxyl group from the boronic acid or from [OH]-containing by-products resulting from its decomposition.

During the isolation of the Aryl-mCB compounds, we identified an air- and chromatographically-stable ruby colored compound that formed as a by-product of the Suzuki-Miyaura cross-coupling reactions. Chromatographic isolation, followed by spectroscopic analysis (11B, 1H, and 31P NMR spectroscopy) suggested a species containing a metal-bound phosphine as well as a boron cluster-containing fragment. Single crystal X-ray crystallography of this material revealed a Pd-based complex containing an XPhos ligand bound in a κ2-(P,C) fashion. The coordination sphere of the Pd-center is completed by a dicarbollide ligand ([nido-7,9-C2B9H11]2-, nido-CB) bound in an η5 fashion. Based on the nature of the phosphine and nido-CB ligands, the formal oxidation state of the Pd-center in [XPhosPd(nido-CB)] is +2. Deboronation of carboranes is known to occur by nucleophilic attack at the electron-poor boron vertices of carboranes (Figure 2, step v).52–54 Small nucleophiles such as F− and OH− can cause deboronation of R-mCB in situ to form the η5-[nido-7,9-C2B9H12]1- ligand that, after deprotonation, binds to the [XPhosPd] complex, vide infra.52,53,55 To probe this pathway further, an independent synthesis of the [XPhosPd(nido-CB)] complex was accomplished by reaction of (nBu4N)[nido-7,9-C2B9H12] with [XPhos-Pd-G3] precatalyst. We found that [XPhosPd(nido-CB)] is not an active catalyst in carborane cross-coupling reactions, likely due to greater coordinative saturation of the Pd center by the nido-CB ligand and the inability to regenerate Pd0 from this species under the reaction conditions.56–58

A unique aspect of [XPhosPd(nido-CB)] is the lack of an exohedral functional group on the nido-CB ligand despite the use of functionalized carborane substrates. This suggests that cage-walking to the B(2) vertex may also activate the carborane toward deboronation and lead to deactivation of the [XPhosPd] catalyst by formation of [XPhosPd(nido-CB)] (Figure 2, step vii). One possible decomposition route may be the cage-walking/cross-coupling of OH− or F− to the B(2) position to generate a B(2)-X’-carborane (X’ = –OH or –F) that is more easily deboronated than B(2)-R-carborane (R = –H or –Aryl).52–55,59–61 Previous studies of carborane deboronation indicate that coordination of several nucleophiles to a B-H vertex is necessary to remove a boron vertex from the carborane cage.54,59,60 Thus, the off-cycle coupling of small nucleophiles, such as OH− or F−, at the B(2) position may activate the B(2)X’-carborane (X’ = –OH or –F) toward deboronation and formation of nido-CB. This highlights the intricacies of using carborane substrates in cross-coupling, particularly in the presence of small nucleophiles can turn a substrate into a catalyst poison. Importantly, this mode of decomposition is distinctly different from the classical cross-coupling chemistry of aryl-based species and necessitates high Pd-catalyst loadings.

Tandem Cage-Walking/Cyanation

Our studies of Br-mCB isomerization and tandem cage-walking/Suzuki-Miyaura coupling have so far revealed that the tandem cage-walking/cross-coupling is possible with sterically unencumbered nucleophiles. With these observations in mind, we set out to integrate the cage-walking cycle into Pd-catalyzed cross-coupling of a small nucleophile (CN−). If successful, the resulting cyano-carborane regioisomers (CN-mCB) can be useful synthons in materials and medicinal chemistry.30,62,63

Cross-coupling of cyanide is a challenging transformation in general given the strong affinity of the CN− ligand to Pd(II), which leads to the formation of catalytically inactive species.64 Efforts to prevent catalyst poisoning have previously focused on reducing and constantly maintaining a small amount of CN− in the reaction mixture.65 For our transformation, we chose Zn(CN)2 as a cyanide source and transmetallation agent due to its strong CN− binding affinity to Zn(II), which prevents formation of free CN− at high Zn(CN)2 concentrations. Additionally, the redox non-activity and the weak binding of phosphine ligands to Zn(II) decreases the likelihood of [XPhosPd] oxidation or phosphine sequestration.66

Although Zn(CN)2 is insoluble in most organic solvents due to the bridging μ2 coordination of CN− across zinc centers, forming Zn-CN-Zn based coordination polymer in the solid state,67 Zn(CN)2 can be solubilized in alkaline and ammoniacal environments.68–73 However, alkaline conditions may lead to undesirable OH-mCB formation or deboronation as observed with the Suzuki-Miyaura cross-coupling reactions, vide supra. Alternatively, trialkylamines are suitable ligands for Zn(CN)2 because they do not inhibit Br-mCB cage-walking, they do not readily participate in the cross-coupling reaction, and they can partially solubilize Zn(CN)2.68,71 Initially we used NEt3 as a base to activate the [XPhos-Pd-G3] precatalyst and to solubilize Zn(CN)2 which lead to a modest yield (<30% yield by GC-MS) of CN-m-carborane (CN-mCB) isomers (Figure 5, Entry #1). Importantly, despite the low yield of CN-mCB, the CN-B(2) and CN-B(4) regioisomers were produced as the major CN-mCB products validating our original hypothesis that under well-designed conditions small nucleophiles can be competent substrates in the discovered cage-walking process.

Figure 5.

Figure 5.

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Optimization of tandem cage-walking/cross-coupling cyanation reaction, the bar graph indicates GC-MS yields of the cyano- ra-carborane regioisomers for each reaction entry. GC-MS reaction monitoring of cyano-m-carborane (CN-mCB) regioisomers produced during tandem cage-walking/cross-coupling.

We then explored whether bidentate alkyl amine ligands can increase the yield of CN-mCB by increasing the solubility of the Zn(CN)2 and by promoting transmetallation of the CN− anion from Zn to Pd. Use of N,N,N’,N’-tetramethylethylenediamine, TMEDA, as a ligand for Zn(CN)2 increased the overall yield of CN-mCB regioisomers (65% by GC-MS), however, the improvement in the CN-mCB yield also increased the amount of CN-B(9) relative to the B(2/4/5) CN-mCB regioisomers (Figure 5, Entry #3). Switching to a larger bidentate alkyl amine N,N,N’,N’-tetraethylethylenediamine, TEEDA, significantly decreased the amount of CN-B(9) relative to the B(2/4/5) CN-mCB regioisomers (Figure 5, Entry #7), but it also decreased the overall CN-mCB yield (<5% by GC-MS). This shows that increasing the steric bulk of the transmetallating agent to promote tandem cage-walking/cross-coupling can have deleterious effects on the overall cross-coupling efficiency. In addition to using alkyl amines, we also examined whether a N-donor heterocycle can increase the CN-mCB yield by increasing the solubility of Zn(CN)2. Use of 4-dimethylaminopyridine, DMAP, as a ligand for the Zn(CN)2 significantly increased the yield of CN-mCB (74% by GCMS), however, the isomer distribution was mostly CN-B(9) (Figure 5, Entry #2). We attribute this difference in regioisomer distribution to suppression of the cage-walking pathway through reversible coordination to [XPhosPd(mCB)]+ and the increased lability of CN− when Zn(CN)2 is ligated by the stronger N-donor DMAP ligand.

Despite improvements in the overall yield of CN-mCB regioisomers, we were unable to obtain complete conversion of Br-B(9) into CN-mCB regioisomers. As the tandem cage-walking/cross-coupling reaction proceeded, we observed darkening of the reaction mixture until a black/grey slurry formed within the first hour of the reaction. GC-MS analysis of a model cage-walking/cyanation reaction shows a gradual decay in the conversion of Br-mCB to CN-mCB until the reaction progress plateaus after ~3 hours (Figure 5). This suggests that the incomplete conversion of Br-mCB to CN-mCB is partially due to Pd0 aggregation to form black Pd0 particles which are not effective catalysts for carborane cross-coupling (Figure 2, step vi).

Suspecting that accumulation of Br− may be inhibiting further conversion of Br-mCB to CN-mCB, we examined whether addition of alkali metal salts can improve the CN-mCB yield by sequestering Br−. Addition of Cs2CO3 or Li(OTf) increased the overall yield of CN-mCB regioisomers without inhibiting the cage-walking process, whereas KOAc had an opposite effect which predominantly produced CN-B(9) (Figure 5, Entry #9). The differences in regioisomer yield with different alkali metal salts and N-donor ligands may be due to the speciation of Zn(CN)2 into mono-, di-, tri- and tetracyano zincate species.71,74–76 The formation of various zinc cyanide species due to ligation by additives and reaction by-products may alter the rate of CN− transmetallation and account for the various CN-mCB regioisomer distributions observed throughout this study. Overall, through our optimization studies we developed several conditions to selectively control the incorporation of the cage-walking process into catalytic cross-coupling with small nucleophiles. In particular, if deactivation of the cage-walking process is desired, addition of Lewis bases (such as DMAP, Figure 5 entry #2) effectively favor B(9) coupling. Alternatively, if the cage-walking process is desired, care should be taken to reduce the amount of Lewis basic species (e. g., Brønsted base or halide counter ion) that can bind the proposed [XPhosPd(mCB)]+ intermediate that leads to isomerization of Br-mCB.

Conclusions

Off-cycle processes in carborane cross-coupling were examined for their role in affecting tandem cage-walking/cross-coupling and in suppressing catalyst activity. The cage-walking process was studied in the absence and presence of a cross-coupling partner to identify conditions that lead to tandem cage-walking/cross-coupling. We found that the Pd-catalyzed cage-walking occurs with several dialkyl biaryl phosphine ligands, and that the cage-walking process can be enhanced or suppressed by the presence of additives such as Ca(OH)2 or DMAP, respectively. These insights allowed identification of substrate transmetallation strategies for tandem cage-walking/cross-coupling reactions with sterically unencumbered nucleophiles such as arylboronic acids and cyanide. The results reported here demonstrate the feasibility of using sterically unencumbered substrates in tandem cage-walking/cross-coupling to synthesize B-substituted carborane regioisomers. These studies further highlight the importance of bulky biaryl-based phosphine ligands originally developed by Buchwald and co-workers in transition metal catalysis extending their application to organomimetic clusters.

Supplementary Material

Supporting Information

ACKNOWLEDGMENTS

We thank NIGMS (R35GM124746) and National Defense Science and Engineering Graduate Fellowship (NDSEG to R. M. D) for supporting this project. This manuscript is dedicated to a mentor and friend, Professor Stephen L. Buchwald, whose seminal contributions to chemistry continue to inspire us all.

Footnotes

ASSOCIATED CONTENT

Supporting Information. Full procedures and crystallographic and other characterizing data are provided in the supporting information, which is available free of charge available free of charge via the Internet at http://pubs.acs.org.

References

  • 1.Metal-Catalyzed Cross-Coupling Reactions; de Meijere A, Diederich F, Eds.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2004. [Google Scholar]
  • 2.Johansson Seechurn CCC; Kitching MO; Colacot TJ; Snieckus V Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize. Angew. Chemie Int. Ed 2012, 51 (21), 5062–5085. [DOI] [PubMed] [Google Scholar]
  • 3.Shultz LH; Brookhart M Measurement of the Barrier to βHydride Elimination in a β-Agostic Palladium-Ethyl Complex: A Model for the Energetics of Chain-Walking in (α-Diimine)PdR+ Olefin Polymerization Catalysts. Organometallics 2001, 20 (19), 3975–3982. [Google Scholar]
  • 4.Crabtree RH Deactivation in Homogeneous Transition Metal Catalysis: Causes, Avoidance, and Cure. Chem. Rev 2015, 115 (1), 127–150. [DOI] [PubMed] [Google Scholar]
  • 5.Balcells D; Nova A Designing Pd and Ni Catalysts for Cross-Coupling Reactions by Minimizing Off-Cycle Species. ACS Catal. 2018, 8 (4), 3499–3515. [Google Scholar]
  • 6.Hassam M; Taher A; Arnott GE; Green IR; van Otterlo WAL Isomerization of Allylbenzenes. Chem. Rev 2015, 115 (11), 5462–5569. [DOI] [PubMed] [Google Scholar]
  • 7.Becica J; Glaze OD; Wozniak DI; Dobereiner GE Selective Isomerization of Terminal Alkenes to (Z)-2-Alkenes Catalyzed by an Air-Stable Molybdenum(0) Complex. Organometallics 2018, 37 (3), 482–490. [Google Scholar]
  • 8.Milner PJ; Kinzel T; Zhang Y; Buchwald SL Studying Regioisomer Formation in the Pd-Catalyzed Fluorination of Aryl Triflates by Deuterium Labeling. J. Am. Chem. Soc 2014, 136 (44), 15757–15766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Li J; Sun C; Demerzhan S; Lee D Metal-Catalyzed Rearrangement of Cyclopropenes to Allenes. J. Am. Chem. Soc 2011, 133 (33), 12964–12967. [DOI] [PubMed] [Google Scholar]
  • 10.Curran K; Risse W; Hamill M; Saunders P; Muldoon J; Asensio De La Rosa R; Tritto I Palladium(II)-Catalyzed Rearrangement and Oligomerization Reactions of Cis Bicyclo[4.2.0]Oct-7-Ene. Organometallics 2012, 31 (3), 882–889. [Google Scholar]
  • 11.Wang JY; Strom AE; Hartwig JF Mechanistic Studies of Palladium-Catalyzed Aminocarbonylation of Aryl Chlorides with Carbon Monoxide and Ammonia. J. Am. Chem. Soc 2018, 140 (25), 7979–7993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Hartwig JF Catalyst-Controlled Site-Selective Bond Activation. Acc. Chem. Res 2017, 50 (3), 549–555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Larsen CR; Grotjahn DB Stereoselective Alkene Isomerization over One Position. J. Am. Chem. Soc 2012, 134 (25), 10357–10360. [DOI] [PubMed] [Google Scholar]
  • 14.Lee CW; Zhuang ZP; Kung MP; Plössl K; Skovronsky D; Gur T; Hou C; Trojanowski JQ; Lee VMY; Kung HF Isomerization of (Z,Z) to (E,E)1-Bromo-2,5-Bis-(3- Hydroxycarbonyl-4-Hydroxy)-Styrylbenzene in Strong Base: Probes for Amyloid Plaques in the Brain. J. Med. Chem 2001, 44 (14), 2270–2275. [DOI] [PubMed] [Google Scholar]
  • 15.Li J; Logan CF; Jones M Simple Syntheses and Alkylation Reactions of 3-Iodo-o-Carborane and 9,12-Diiodo-o-Carborane. Inorg. Chem 1991, 30 (25), 4866–4868. [Google Scholar]
  • 16.Eriksson L; Beletskaya I; Bregadze V; Sivaev I; Sjoberg S Palladium-Catalyzed Cross-Coupling Reactions of Arylboronic Acids and 2-I-p-Carborane. J. Organomet. Chem 2002, 657 (1–2), 267–272. [Google Scholar]
  • 17.Lin F; Yu J-L; Shen Y; Zhang S-Q; Spingler B; Liu J; Hong X; Duttwyler S Palladium-Catalyzed Selective FiveFold Cascade Arylation of the 12-Vertex Monocarborane Anion by B–H Activation. J. Am. Chem. Soc 2018, 140 (42), 13798–13807. [DOI] [PubMed] [Google Scholar]
  • 18.Cheng R; Li B; Wu J; Zhang J; Qiu Z; Tang W; You SL; Tang Y; Xie Z Enantioselective Synthesis of Chiral-atCage o -Carboranes via Pd-Catalyzed Asymmetric B-H Substitution. J. Am. Chem. Soc 2018, 140 (13), 4508–4511. [DOI] [PubMed] [Google Scholar]
  • 19.Anderson KP; Mills HA; Mao C; Kirlikovali KO; Axtell JC; Rheingold AL; Spokoyny AM Improved Synthesis of Icosahedral Carboranes Containing Exopolyhedral B–C and C–C Bonds. Tetrahedron 2019, 75 (2), 187–191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Beletskaya IP; Bregadze VI; Ivushkin VA; Zhigareva GG; Petrovskii P V; Sivaev, I. B. Palladium-Catalyzed Alkynylation of 2-Iodo-p-Carboranes and 9-Iodo-m-Carboranes. Russ. J. Org. Chem 2005, 41 (9), 1359–1366. [Google Scholar]
  • 21.Sevryugina Y; Julius RL; Hawthorne MF Novel Approach to Aminocarboranes by Mild Amidation of Selected IodoCarboranes. Inorg. Chem 2010, 49 (22), 10627–10634. [DOI] [PubMed] [Google Scholar]
  • 22.Kabytaev KZ; Everett TA; Safronov AV; Sevryugina YV; Jalisatgi SS; Hawthorne MF B-Mercaptocarboranes: A New Synthetic Route. Eur. J. Inorg. Chem 2013, No. 14, 2488–2491. [Google Scholar]
  • 23.Safronov AV; Kabytaev KZ; Jalisatgi SS; Hawthorne MF Novel Iodinated Carboranes: Synthesis of the 8-Iodo-7,9Dicarba-Nido-Undecaborate Anion and 2-Iodo-1,7-DicarbaCloso-Dodecaborane. Dalt. Trans 2014, 43 (33), 12467. [DOI] [PubMed] [Google Scholar]
  • 24.Wingen LM; Scholz MS B-Cyanodicarba-Closo-Dodecaboranes: Facile Synthesis and Spectroscopic Features. Inorg. Chem 2016, 55 (17), 8274–8276. [DOI] [PubMed] [Google Scholar]
  • 25.Saleh LMA; Dziedzic RM; Khan SI; Spokoyny AM Forging Unsupported Metal–Boryl Bonds with Icosahedral Carboranes. Chem. - A Eur. J 2016, 22 (25), 8466–8470. [DOI] [PubMed] [Google Scholar]
  • 26.Dziedzic RM; Saleh LMA; Axtell JC; Martin JL; Stevens SL; Royappa AT; Rheingold AL; Spokoyny AM B-N, B-O, and B-CN Bond Formation via Palladium-Catalyzed Cross-Coupling of B-Bromo-Carboranes. J. Am. Chem. Soc 2016, 138 (29), 9081–9084. [DOI] [PubMed] [Google Scholar]
  • 27.Ishita K; Khalil A; Tiwari R; Gallucci J; Tjarks W Bis(Tri- Tert -Butylphosphine)Palladium(0)-Catalyzed Iodine-Fluorine Exchange at Closo -Carboranes. Eur. J. Inorg. Chem 2018, 2018 (24), 2821–2825. [Google Scholar]
  • 28.Leites LA; Introductlon I; Boranes I; Boranes I; Modes B; Boranes GI; Heteroatoms C Vibrational Spectroscopy of Carboranes and Parent Boranes and Its Capabilities in Carborane Chemistry. Chem. Rev 1992, 92 (2), 279–323. [Google Scholar]
  • 29.Bendel P Biomedical Applications of 10B and 11B NMR. NMR Biomed 2005, 18 (2), 74–82. [DOI] [PubMed] [Google Scholar]
  • 30.Leśnikowski ZJ Challenges and Opportunities for the Application of Boron Clusters in Drug Design. J. Med. Chem 2016, 59 (17), 7738–7758. [DOI] [PubMed] [Google Scholar]
  • 31.Messina MS; Graefe CT; Chong P; Ebrahim OM; Pathuri RS; Bernier NA; Mills HA; Rheingold AL; Frontiera RR; Maynard HD; et al. Carborane RAFT Agents as Tunable and Functional Molecular Probes for Polymer Materials. Polym. Chem 2019, 10 (13), 1660–1667. [Google Scholar]
  • 32.Serino AC; Anderson ME; Saleh LMA; Dziedzic RM; Mills H; Heidenreich LK; Spokoyny AM; Weiss PS Work Function Control of Germanium through CarboraneCarboxylic Acid Surface Passivation. ACS Appl. Mater. Interfaces 2017, 9 (40), 34592–34596. [DOI] [PubMed] [Google Scholar]
  • 33.Quan Y; Qiu Z; Xie Z Transition-Metal-Catalyzed Selective Cage B−H Functionalization of o-Carboranes. Chem. - A Eur. J 2018, 24 (12), 2795–2805. [DOI] [PubMed] [Google Scholar]
  • 34.Duttwyler S Recent Advances in B-H Functionalization of Icosahedral Carboranes and Boranes by Transition Metal Catalysis. Pure Appl. Chem 2018, 90 (4), 733–744. [Google Scholar]
  • 35.Quan Y; Xie Z Controlled Functionalization of o -Carborane via Transition Metal Catalyzed B–H Activation. Chem. Soc. Rev 2019, 3660–3673. [DOI] [PubMed] [Google Scholar]
  • 36.Lyu H; Zhang J; Yang J; Quan Y; Xie Z Catalytic Regioselective Cage B(8)-H Arylation of o-Carboranes via “Cage-Walking” Strategy. J. Am. Chem. Soc. 2019, 141 (10), 4219–4224. [DOI] [PubMed] [Google Scholar]
  • 37.Eleazer BJ; Smith MD; Popov AA; Peryshkov DV Expansion of the (BB)Ru Metallacycle with Coinage Metal Cations: Formation of B-M-Ru-B (M = Cu, Ag, Au) Dimetalacyclodiboryls. Chem. Sci 2018, 9 (9), 2601–2608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Dziedzic RM; Spokoyny AM Metal-Catalyzed Cross-Coupling Chemistry with Polyhedral Boranes. Chem. Commun 2019, 55 (4), 430–442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Safronov AV; Sevryugina YV; Jalisatgi SS; Kennedy RD; Barnes CL; Hawthorne MF Unfairly Forgotten Member of the Iodocarborane Family: Synthesis and Structural Characterization of 8-Iodo-1,2-Dicarba- Closo - Dodecaborane, Its Precursors, and Derivatives. 2012. [DOI] [PubMed] [Google Scholar]
  • 40.Safronov AV; Kabytaev KZ; Jalisatgi SS; Hawthorne MF Novel Iodinated Carboranes: Synthesis of the 8-Iodo-7,9-Dicarba-Nido- Undecaborate Anion and 2-Iodo-1,7-DicarbaCloso-Dodecaborane. Dalt. Trans 2014, 43 (33), 12467–12469. [DOI] [PubMed] [Google Scholar]
  • 41.Lipscomb WN Framework Rearrangement in Boranes and Carboranes. Science (80-. ). 1966, 153 (3734), 373–378. [DOI] [PubMed] [Google Scholar]
  • 42.Kalinin VN; Kobel’kova NI; Zakharkin LI Synthesis of 2- and 4-Aryl-m-Carboranes and Electronic Effects of the 4-mCarboranyl Group. J. Organomet. Chem 1979, 172 (4), 391–395. [Google Scholar]
  • 43.Baše T; Macháček J; Hájková Z; Langecker J; Kennedy JD; Carr MJ Thermal Isomerizations of Monothiolated Carboranes (HS)C2B10H11 and the Solid-State Investigation of 9-(HS)-1,2-C2B10H11 and 9-(HS)-1,7-C2B10H11. J. Organomet. Chem 2015, 798, 132–140. [Google Scholar]
  • 44.Bakardjiev M; Štíbr B; Holub J; Padělková Z; Růžička A Simple Synthesis, Halogenation, and Rearrangement of Closo1,6-C2B8H10. Organometallics 2015, 34 (2), 450–454. [Google Scholar]
  • 45.Dziedzic RM; Martin JL; Axtell JC; Saleh LMA; Ong TC; Yang YF; Messina MS; Rheingold AL; Houk KN; Spokoyny AM Cage-Walking: Vertex Differentiation by Palladium-Catalyzed Isomerization of B(9)-Bromo-MetaCarborane. J. Am. Chem. Soc 2017, 139 (23), 7729–7732. [DOI] [PubMed] [Google Scholar]
  • 46.Bruno NC; Tudge MT; Buchwald SL Design and Preparation of New Palladium Precatalysts for C-C and C-N Cross-Coupling Reactions. Chem. Sci 2013, 4 (3), 916–920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Lee HG; Milner PJ; Buchwald SL An Improved Catalyst System for the Pd-Catalyzed Fluorination of (Hetero)Aryl Triflates. Org. Lett 2013, 15 (21), 5602–5605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Rajamathi M; Kamath PV; Seshadri R Polymorphism in Nickel Hydroxide: Role of Interstratification. J. Mater. Chem 2000, 10 (2), 503–506. [Google Scholar]
  • 49.Düfert MA; Billingsley KL; Buchwald SL Suzuki-Miyaura Cross-Coupling of Unprotected, Nitrogen-Rich Heterocycles: Substrate Scope and Mechanistic Investigation. J. Am. Chem. Soc 2013, 135 (34), 12877–12885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Beletskaya IP; Bregadze VI; Kabytaev KZ; Zhigareva GG; Petrovskii PV; Glukhov IV; Starikova ZA Palladium-Catalyzed Amination of 2-Iodo-Para-Carborane. Organometallics 2007, 26 (9), 2340–2347. [Google Scholar]
  • 51.Darwent B, de B. Bond Dissociation Energies in Simple Molecules. In National Standard Reference Data Series - National Bureau of Standards; 1970; Vol. 31, p 48. [Google Scholar]
  • 52.Fox MA; Gill WR; Herbertson PL; MacBride JAH; Wade K; Colquhoun HM Deboronation of C-Substituted Ortho- and Meta-Closo-Carboranes Using “Wet” Fluoride Ion Solutions. Polyhedron 1996, 15 (4), 565–571. [Google Scholar]
  • 53.Fox MA; Wade K Deboronation of 9-Substituted-Ortho- and -Meta-Carboranes. J. Organomet. Chem 1999, 573 (1–2), 279–291. [Google Scholar]
  • 54.Taoda Y; Sawabe T; Endo Y; Yamaguchi K; Fujii S; Kagechika H Identification of an Intermediate in the Deboronation of Ortho-Carborane: An Adduct of Ortho-Carborane with Two Nucleophiles on One Boron Atom. Chem. Commun 2008, No. 17, 2049–2051. [DOI] [PubMed] [Google Scholar]
  • 55.Yoo J; Hwang JW; Do Y Facile and Mild Deboronation of O-Carboranes Using Cesium Fluoride. Inorg. Chem 2001, 40 (3), 568–570. [DOI] [PubMed] [Google Scholar]
  • 56.Warren L Jr; Hawthorne M Metallocene Analogs of Copper, Gold, and Palladium Derived from the (3)-1, 2-Dicarbollide Ion. J. Am. Chem 1968, 90 (18), 4823–4828. [Google Scholar]
  • 57.Jasper SA; Huffman JC; Todd LJ Palladium-Assisted Cyano Substitution Reactions of (PMe2Ph)2Pd(B9H9As2) and (PMe2Ph)2Pd(B9C2H11). X-Ray Crystal and Molecular Structures of 5-CN-1,1-(PMe2Ph)2-Closo-1,2,3-PdAs2B9H8, 1TBuNC-5-CN-1-(PMe2Ph)-Closo-1,2,3-PdAs2B9H8, and 4,5(CN)2–1,1-(PMe2Ph). Inorg. Chem 1995, 34 (26), 6430–6439. [Google Scholar]
  • 58.Jasper SA; Huffman JC; Todd LJ Synthesis of a Metallaborane Complex Containing Pd(III) and the First Doubly Charge Compensated Ollide Ion. X-Ray Crystal Structure of 1,4Br 2 −1,2,5-(PMe 2 Ph) 3 - Closo −1-PdB 11 H 8. Inorg. Chem 1998, 37 (23), 6060–6064. [DOI] [PubMed] [Google Scholar]
  • 59.Willans CE; Kilner CA; Fox MA Deboronation and Deprotonation of Ortho-Carborane with N-Heterocyclic Carbenes. Chem. - A Eur. J 2010, 16 (35), 10644–10648. [DOI] [PubMed] [Google Scholar]
  • 60.Zheng F; Xie Z Reaction of O-Carboranes with Sterically Demanding N-Heterocyclic Carbene: Synthesis and Structural Characterization of 1:1 Adducts. Dalt. Trans 2012, 41 (41), 12907–12914. [DOI] [PubMed] [Google Scholar]
  • 61.Zhang CY; Cao K; Xu TT; Wu J; Jiang L; Yang J A Facile Approach for the Synthesis of Nido-Carborane Fused Oxazoles via One Pot Deboronation/Cyclization of 9-Amide-oCarboranes. Chem. Commun 2019, 55 (6), 830–833. [DOI] [PubMed] [Google Scholar]
  • 62.Issa F; Kassiou M; Rendina LM Boron in Drug Discovery: Carboranes as Unique Pharmacophores in Biologically Active Compounds. Chem. Rev 2011, 111 (9), 5701–5722. [DOI] [PubMed] [Google Scholar]
  • 63.Scholz M; Hey-Hawkins E Carbaboranes as Pharmacophores: Properties, Synthesis, and Application Strategies. Chemical Reviews. November 9, 2011, pp 7035–7062. [DOI] [PubMed] [Google Scholar]
  • 64.Erhardt S; Grushin VV; Kilpatrick AH; Macgregor SA; Marshall WJ; Roe DC Mechanisms of Catalyst Poisoning in Palladium-Catalyzed Cyanation of Haloarenes. Remarkably Facile C-N Bond Activation in the [(Ph3P) 4Pd]/[Bu4N]+ CN- System. J. Am. Chem. Soc 2008, 130 (14), 4828–4845. [DOI] [PubMed] [Google Scholar]
  • 65.Anbarasan P; Schareina T; Beller M Recent Developments and Perspectives in Palladium-Catalyzed Cyanation of Aryl Halides: Synthesis of Benzonitriles. Chem. Soc. Rev 2011, 40 (10), 5049–5067. [DOI] [PubMed] [Google Scholar]
  • 66.Heaney H Zinc Cyanide. In Encyclopedia of Reagents for Organic Synthesis; John Wiley & Sons, Ltd: Chichester, UK, 2001; Vol. 3, p 533. [Google Scholar]
  • 67.Hoskins BF; Robson R Design and Construction of a New Class of Scaffolding-like Materials Comprising Infinite Polymeric Frameworks of 3D-Linked Molecular Rods. A Reappraisal of the Zn(CN)2 and Cd(CN)2 Structures and the Synthesis and Structure of the Diamond-Related Framework. J. Am. Chem. Soc. 1990, 112 (4), 1546–1554. [Google Scholar]
  • 68.Ahuja IS; Singh R Bidentate Bridged Morpholine Complexes with Zinc(II) and Cadmium(II) Cyanides. J. Coord. Chem. 1976, 5 (3), 167–170. [Google Scholar]
  • 69.Monge A; Martínez-Ripoll M; García-Blanco S The Adduct Zinc Dicyanide–Bis(2,9-Dimethyl-1,10-Phenanthroline) Trihydrate. Acta Crystallogr. Sect. B Struct. Crystallogr. Cryst. Chem 1978, 34 (9), 2847–2850. [Google Scholar]
  • 70.Ho K; Yu W; Cheung K; Che C A Blue Photoluminescent [Zn(L)(CN)2] (L = 2,2′-Dipyridylamine) Material with a Supramolecular One-Dimensional Chain Structure. Chem. Commun 1998, 3 (19), 2101–2102. [Google Scholar]
  • 71.Jasiewicz B; Boczoń W; Mumot A; Warzajtis B; Rychlewska U Synthesis, Spectroscopy and Crystal Structure of α-Isosparteine Complexes with ZnX2 (X=Br, CN, Cl). J. Mol. Struct 2005, 737 (2–3), 239–244. [Google Scholar]
  • 72.Das S; Nag A; Goswami D; Bharadwaj PK Zinc(II)- and Copper(I)-Mediated Large Two-Photon Absorption Cross Sections in a Bis-Cinnamaldiminato Schiff Base. J. Am. Chem. Soc 2006, 128 (2), 402–403. [DOI] [PubMed] [Google Scholar]
  • 73.Sayin E; Kürkçüoʇlu GS; Yeşilel OZ; Hökelek T Synthesis, Crystal Structure and Spectroscopic Properties of One-Dimensional Zinc(II)-Cyanide Complex with 1-Methylimidazole, [Zn(μ-CN)(CN) (1-Meim)]N. Zeitschrift fur Krist. - Cryst. Mater 2015, 230 (6), 421–426. [Google Scholar]
  • 74.Pickardt J; Staub B Kristallstruktur Des Cyanoverbrückten Polymeren Zinkcyanid-Pyridin-Komplexes [Zn(Py)2][Zn(CN)4] / Crystal Structure of the Cyano Linked Polymeric Zinc Cyanide Pyridine Complex [Zn(Py)2][Zn(CN)4]. Zeitschrift für Naturforsch. B 1995, 50 (10), 1517–1520. [Google Scholar]
  • 75.Guo Y; Weiss R; Boese R; Epple M Synthesis, Structural Characterization and Thermochemical Reactivity of Tris(Ethylenediamine)Zinc Tetracyanozincate, a Precursor for Nanoscale ZnO. Thermochim. Acta 2006, 446 (1–2), 101–105. [Google Scholar]
  • 76.Kürkçüoʇlu GS; Yeşilel OZ; Şahin O; Sayin E; Büyükgüngör O Dinuclear Zinc(II) Complex with Tris(2Aminoethyl) Amine Ligand: Synthesis, Structure and Properties. Zeitschrift fur Krist. - Cryst. Mater 2015, 230 (6), 407–412. [Google Scholar]

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