Site- and enantioselective B−H functionalization of carboranes

doi:10.21203/rs.3.rs-3464559/v1

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Site- and enantioselective B−H functionalization of carboranes

https://doi.org/10.21203/rs.3.rs-3464559/v1

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Functionalization of carboranes, icosahedral boron − carbon molecular clusters, is of great interest as they have wide applications in medicinal and materials chemistry. Thus, site- and enantioselective synthesis of carboranes requires complete control of the reaction. Herein, we describe the first asymmetric Rh(II)-catalyzed insertion reactions of carbenes into cage B − H bond of carboranes. This reaction thereby generates carboranes possessing a carbon-stereocenter adjacent to cage boron of the carborane, in excellent site- and enantioselectivity under mild reaction conditions. The first fully computed transition structures of Rh(II)-catalyzed carbene insertion process through density functional theory are reported. These B − H insertion transition structures, in conjunction with newly employed topographical proximity surfaces analyses, visually reveal the region between the carborane and the phthalimide ligands responsible for the selectivities of this reaction.

Physical sciences/Chemistry/Organic chemistry/Synthetic chemistry methodology

Physical sciences/Chemistry/Catalysis/Asymmetric catalysis

Physical sciences/Chemistry/Catalysis/Catalytic mechanisms

Physical sciences/Chemistry/Organic chemistry/Stereochemistry

Control of selectivity in reactions is of utmost importance in chemistry and the ultimate driving force for developing new reactions. Asymmetric catalytic reactions to control the stereoselectivity with chiral organic molecules, chiral auxiliaries, chiral reagents, and chiral metal complexes have been recognized as the most solid method in asymmetric synthesis^1–4. Their syntheses involve breaking the point, axial, planar, and helical symmetry elements of symmetric molecules. Among these, transition metal-catalyzed enantioselective reactions have emerged as one of the most powerful approaches to get optically pure compounds^2,4. To date, a huge myriad of chiral structures including central, axial, planar, and helical chirality have been achieved by catalytic asymmetric synthesis^5,6. However, site-selective reactions to break the symmetry in hypersymmetric three-dimensional cluster compounds, such as the icosahedral carboranes, with exohedral stereocontrol is a formidable challenge due to various classes of chirality such as plane chirality, cage chirality, and carbon chirality adjacent to the cage carbon or boron.

Carboranes are icosahedral boron − carbon molecular clusters, attractive building blocks combining properties such as chemical and biological stability, lipophilicity and hydrophobicity solubility properties, hydridic B–H bonds, spherical geometry, and three dimensional σ-aromaticity^7,8. Carboranes have been utilized in boron neutron capture therapy agents in medicine⁹, as unique pharmacophores¹⁰, as ligands in transition metal catalysis^11–13, and even confer unique and powerful structural and photooptical properties in supramolecular design and materials (Fig. 1a)^14–17. However, despite these distinctive function that carboranes can confer, we are crippled in our ability to access the full potential of carboranes because we do not have means to site-selectively react on carboranes and build complexity rapidly.

Accordingly, a variety of research and applications based on these facts have increased the interest in the site- and enantioselective functionalization on ten boron vertexes of carborane (Fig. 1b)^18,19. However, significant advances in the synthesis of chiral molecules possessing carborane moieties have only recently achieved despite of recent progress for the functionalization of carboranes^20–24. For the first time, Kalinin and co-workers carried out the direct asymmetric synthesis (up to 32% e.e.) for o-carborane derivatives bearing chirality on C-proximity by Pd-catalyzed allylation reaction in the presence of chiral ligand (Fig. 1c)²⁵. If the substituents on the cage carbon atoms are different, substitution at B(3) position provides a pair of enantiomer possessing chiral center on the plane. In this regard, Krasnov and co-workers were the first to obtain planar-chiral 3-amino-1-methyl-1,2-dicarba-closo-dodecaborane in enantiomerically moderate form through a chiral resolution²⁶. On the other hand, Xie, Qiu, and co-workers developed for the first time an enantioselective synthesis of chiral-at-cage o-carboranes through Pd-catalyzed intramolecular cross-coupling reactions with (R)-BI-DIME as a chiral ligand²⁷. Furthermore, they reported Ir-catalyzed enantioselective B − H alkenylation with chiral phosphoramidite ligand, affording chiral-at-cage B(4)-alkenyl o-carboranes²⁸. In these seminal reports, the functionalization was achieved either intramolecularly or made use of a directing group to control the site-selectivity. In contrast, there has been no success in achieving stereoselective introduction of an exohedral chiral center, which is a carbon-stereocenter adjacent to cage boron of the carborane, through direct B − H functionalization that is highly enantioselective and in the absence of any directing group. Rudimentary control of enantioselectivity using carboranes as the steric element or control of regioselectivity in B–H bond activation have been reported. However, true complexity building synthetic processes which can activate B–H bonds on carboranes in a regiocontrolled manner while simultaneously creating exohedral chiral centers are unknown at this time.

Although some reactions of carbenes with unsubstituted carboranes have been reported, the yield and site-selectivity were lackluster without stereoselectivity issue (see the Supplementary Information, Fig. S1). For example, Jones reported the reaction of o-carborane with ethyl diazoacetate under irradiation, providing inseparable four regioisomers in combined 10% yield (12:7.2:4.8:1)²⁹. Moreover, he found that methylene carbene could insert into B − H bonds of m-carborane under irradiation, producing inseparable regioisomeric mixture³⁰. Reaction of p-carborane with methylene carbene under irradiation afforded B-alkylated product in low yield even giving single product due to identical ten B − H bonds. Therefore, the development of concise and efficient method that controls site- and enantioselectivity in functionalization of carborane is extremely attractive and a significant challenge.

We describe herein the first effective site- and enantioselective B − H functionalization, thereby generating o-, m-, and p-carboranes possessing an exohedral carbon-stereocenter, which is a carbon-stereocenter adjacent to cage boron of the carborane, in excellent enantioselectivity (99% e.e.), site-selectivity (> 50:1 r.r.) and in excellent yields with broad substrate scope under mild reaction conditions (Fig. 1d). We are also pleased to report the first fully quantum mechanically computed transition structures of this chiral dirhodium carbenoid insertion process into an icosahedral cage B–H bond of carboranes. Our density functional theory (DFT) results reproduce experimentally observed site- and enantioselectivity of the B–H functionalization. We employed a topographical tool to visualize and highlight the structurally subtle, but energetically critical, steric close contacts to elucidate the specific structural elements involved. This topographical proximity surfaces (TPS) analysis visually revealed the specific steric interactions between the carborane and the phthalimide ligand responsible for the observed selectivities.

Reaction optimization

To develop a site- and enantioselective carbene insertion reaction into B − H bond of o-carboranes, reaction conditions were extensively explored (see Supplementary Information Table S1 for details). Our investigation began with the reaction of 1,2-(DMPS)₂-o-C₂B₁₀H₁₀ (1a, DMPS = dimethylphenylsilyl) with methyl 2-diazo-2-phenylacetate (2a) in dichloromethane (DCM) at 40 ^oC using various dirhodium tetracarboxylate catalysts. Upon detailed examination of these reactions, we found that two regioisomers [3aa-B(9) and 4aa-B(8)] were obtained as an inseparable mixture, while no other regioisomers were observed. The regioisomeric ratio (r.r.) of 3aa and 4aa and the enantiomeric excess (e.e.) of 3aa were determined through ¹H NMR and chiral HPLC analysis, respectively. Among the achiral catalysts, Rh₂(OAc)₄ gave the mixture of regioisomers in 87% yield with 2.6:1 r.r. as racemate (entry 1). On the other hand, Rh₂(oct)₄ provided a relatively low yield (71%) but high site-selectivity (14:1) (entry 2). Furthermore, we investigated various chiral catalysts to achieve the enantioselective reaction (entries 3–11)³¹. As a result of examining chiral Rh(II) catalysts, it was revealed that Rh₂(S-TCPTTL)₄ showed quantitative yield, high site-selectivity (29:1), and enantioselectivity (25% e.e.) (entry 10). Rh₂(R-BTPCP)₄, the most sterically encumbering catalyst, gave trace amount of conversion of 1a, probably due to the steric effect of carborane cluster (entry 11)³². The enantioselectivity of the present reaction was affected by the solvents such as dichloroethane (DCE), cyclohexane, benzene, and trifluorotoluene (PhCF₃). Especially, benzene and PhCF₃ enhanced the enantioselectivity to 44% e.e. and 42% e.e., respectively, and then PhCF₃ was chosen as an optimum solvent (entry 15)³³. When the reaction temperature was lowered from 40°C to 0°C, the enantiomeric excess increased from 42–51% (entry 17). We were pleased to observe that quantitative yield was obtained even with 1.0 mol % catalyst loading (entry 19). When 2a (1.5 equiv) was used, the yield was reduced to 79% (entry 21).

Substrate scope

Based on these results, the substrate scope of o-carboranes was next investigated (Fig. 2). When unsubstituted, silyl- or benzyl-disubstituted o-carboranes (1a-1d) were treated with methyl 2-diazo-2-phenylacetate (2a), the yields of the desired products (3aa-3da) were all quantitative, but the selectivity was affected by the substituents of o-carborane. We found that 1,2-(TMS)₂-o-C₂B₁₀H₁₀ (1b; TMS = trimethylsilyl) gave rise to 3ba in high site- and enantioselectivity (22:1 r.r. and 55% e.e.). After close examination of diazo substrate scope in the reaction with 1b, it is disclosed that substituents on aryl and ester group play an important role in enantioselectivity (3bb-3bo). As a result, 2,2,2-trichloroethyl 2-(4-bromophenyl)-2-diazoacetate (2d) underwent the B − H insertion reaction to produce the desired product 3bd in 96% yield with high site- and enantioselectivity (25:1 r.r. and 99% e.e.). This result indicates that trichloroethyl (TCE) group is very effective to the B − H insertion³⁴. When there was no substituent on the aryl group, the desired 3be was obtained in 98% yield with 25:1 r.r. and 89% e.e., suggesting that para-substituents on aryl group are essential for excellent enantioselectivity. Then, we evaluated various electron-withdrawing groups on para-position of the aryl ring. TCE aryl diazoacetates possessing chloro, iodo, trifluoromethyl, ketone, and ester groups provided the corresponding B − H insertion products (3bf-3bj) in high yields ranging from 89–99% with excellent site- and enantioselectivity (up to > 50:1 r.r. and 99% e.e.). p-Nitro-substituted diazoacetate (2k) was reacted with 1b at 40°C, resulting in the formation of the desired product (3bk) in 69% yield with > 50:1 r.r. and 93% e.e.. In addition, a variety of electron-donating groups such as methyl, tert-butyl, phenyl, and methoxy group on para-position were tolerable, affording the desired carboranes (3bl-3bo) in high yields with site- and enantioselectivities. Diazo compounds possessing bromo, methyl, and methoxy groups on meta-position (2p-2r) and fluoro, bromo, and methyl groups on ortho-position (2s-2u) gave the corresponding products (3bp-3bu) in good to excellent site-selectivities, enantioselectivities (up to 97% e.e.), and yields (up to 99%). TCE aryl diazoacetates that possess 3,4-dichlorophenyl, 3,5-dimethylphenyl, and 2-naphthyl groups were also compatible with the present reaction conditions (3bv-3bx). TCE heteroaryl diazoacetates including thiophene and pyridine (2y and 2z) successfully applied to the present reaction. The enantiomeric excesses of 3bk, 3bq, 3bt, and 3by were determined after desilylation because of the difficulty in separation of enantiomers.

Encouraged by these results, a wide range of carboranes were investigated in the reaction with 2,2,2-trichloroethyl 2-(4-bromophenyl)-2-diazoacetate (2d) to verify if the excellent site- and enantiooselectivity would be maintained. When o-C₂B₁₀H₁₂, 1,2-dibenzyl- and 1,2-dimethyl-o-C₂B₁₀H₁₀ (1c-1e) were treated with 2d, the desired products (3cd-3ed) were obtained in high yield with 99% e.e.. However, these substrates exhibited inferior site-selectivity (4.9:1 ~ 6.3:1 r.r.), suggesting that silyl groups on the cage carbon of the carborane play a critical role. To demonstrate the versatility of these Rh-catalyzed cage B − H insertion reactions, we examined whether the substrates possessing substituent on the cage boron could be employed. It is noteworthy that both 1f and 1g were smoothly converted to the desired products (3fd and 3gd) in 89% and 97% yields, respectively, without any regioisomers. Although 3,6-diphenyl-o-C₂B₁₀H₁₀ (1f) showed 35% enantioselectivity, 1-methyl-7,11-diphenyl-o-C₂B₁₀H₉ (1g) exhibited excellent enantioselectivity (99% e.e.). The structures of (R)-3bd and (R)-3gd were confirmed by X-ray crystallography (see Supplementary Information). Crystal structure of (R)-3gd was obtained after transformation of ester to carboxylic acid because of difficulty in crystal formation.

Next, we applied the present method to m- and p-carboranes (Fig. 2). Gratifyingly, the carbenes on phthalimido Rh catalyst smoothly underwent B − H insertion reactions with m- and p-carboranes. When m-C₂B₁₀H₁₂ (1h) was treated with 2d under optimum reaction conditions, the corresponding product 3hd was obtained in 76% yield with excellent enantioselectivity (99% e.e.). 1,7-(TMS)₂-m-C₂B₁₀H₁₀ (1i) was transformed to the desired product (3id) in 92% yield with 95% e.e. with 3.0 equivalents of 2d. p-Carborane (1j) having equivalent ten B − H bonds can react with two or more carbenes to give multialkylated products. To suppress repetitive B − H insertion reaction, steric influence of the rhodium catalyst was enhanced, and it was revealed that Rh₂(S-TPPTTL)₄ is suitable for mono-selective B − H insertion reactions of p-carboranes, affording 3jb-3jd in good yield with high enantioselectivity (up to 97% e.e.). The structures of (R)-3hd and (R)-3jd were confirmed by X-ray crystallography (see Supplementary Information).

To prove the practicability of the present catalytic procedure, the B − H insertion reaction of o-carboranes was examined on a large scale using 1.01 g (3.50 mmol) of 1b. After completion of Rh-catalyzed B − H insertion reaction, the one-pot desilylation reaction was successfully carried out, leading to the desilylated products 5 and 6 in high yields (85% and 91%, each) with excellent enantioselectivity (99% e.e.).

CD spectra, reactivity comparison, and synthetic applications

Circular dichroism (CD) spectra of (R)-3bd and (S)-3bd obtained with Rh₂(S-TCPTTL)₄ and Rh₂(R-TCPTTL)₄ catalyst exhibited unambiguously mirror images to each other, indicating a pair of enantiomers (Fig. 3a). Furthermore, the absolute configuration of (R)-3bd and (S)-3bd was confirmed by X-ray crystallography.

To examine the reactivity of carboranes with rhodium carbenoids, competition experiments were conducted with various carbenophiles using 1.0 equivalent of 2d under the optimum reaction conditions (Fig. 3b). First, we initiated competition experiment with 1,4-cyclohexadiene (1,4-CHD) that rapidly undergoes allylic C − H insertion reactions with rhodium carbenoids³⁵. As a result, 7 was obtained in 70% yield without the formation of 3bd, suggesting that reactivity of 1,4-CHD is strong compared to 1b. Next, competition reaction of 1b with dioxolane furnished 3bd (21%) and 8 (47%). This result implies that reactivity of dioxolane has slightly better than that of 1b. Finally, since 3bd was only produced from competition experiment of 1b and tetrahydrofuran (THF), relative reactivity order of these carbenophiles could be listed as follows 1,4-CHD > > dioxolane > TMS-carborane (1b) > > THF.

To explore the application of these reactions, further functionalization of 5 and 6 was attempted. When 5 was treated with DIBAL-H, the corresponding alcohol 10 was obtained in 75% yield without erosion of the stereochemical fidelity. Trichloroethyl ester was successfully transformed to carboxylic acid 11 in 89% yield using zinc and acetic acid also with no erosion of enantiomeric excess. Enantiomeric excess of 6 was slightly deteriorated under coupling reaction conditions. As a result of Sonogashira and Buchwald-Hartwig cross-coupling reactions with 6, desired internal alkyne 12 and diaryl amine 13 were produced in 86% (89% e.e.) and 68% yields (86% e.e.), respectively.

Mechanistic studies

A deuterium labeling experiment revealed that B − H insertion reaction occurs through concerted mechanism because the deuterium atom substituted at B(9)-position of o-carborane 1b-[D]_n was transferred to the α-carbon adjacent to cage boron of the product 3bd-[D_n] without a change in the H/D ratio. When 1b-[D]_n or 1b was treated with H₂O or D₂O under the optimum reaction conditions, deuterium scrambling was not observed at all (Fig. 4a).

In addition to the experimental data, computations were also conducted to understand the site- and enantioselectivity of this dirhodium-catalyzed carbenoid B–H insertion reaction into icosahedral cage o-carborane using density functional theory (DFT). The applicability of DFT for studying dirhodium-catalyzed reactions and C–H bond insertions have been explored by others^36–46. It is noteworthy that despite significant efforts by multiple research groups, these pioneering efforts reveal the enormous challenges and complexities involved with computing transition structures of large and conformationally flexible systems. Most computational studies of dirhodium carbenoid insertion processes have been rationalizations from ground state structures. To date, there are only two computed transition state studies involving the full dirhodium-catalyzed carbenoid insertion for C–H bonds, and none for B–H bond insertions using carboranes. Houk, Davies, and co-workers reported an enantioselective functionalization of a non-activated primary C–H bond using an alkyl substrate, but this study involved a relatively conformationally rigid catalyst and a judicious choice of QM/MM methodology to deal with the cost of computing such large structures⁴⁰. Tantillo and co-workers reported ab initio molecular dynamics simulations to rationalize the origins of selectivity in a C–H functionalization involving an intramolecular 1,4-shift⁴⁶. Herein, we are pleased to report the first fully quantum mechanically computed transition structures of a chiral dirhodium-catalyzed carbenoid B–H insertion reaction of carboranes involving the complete experimentally used ligands and substrates with no structural simplifications. Our DFT results reproduce experimentally observed site- and enantioselectivity. In addition, we reveal a tool to visualize and highlight the structurally subtle, but energetically critical, steric close contacts in a topographical view to elucidate the specific functional groups and moieties. All computations and structures presented in this paper were performed at the PBE-D3BJ level of theory in conjunction with the LANL2DZ(Rh, Br, Cl) & 6-31G* (for all other atoms) basis sets as implemented in Gaussian 16. CPCM(C₆H₆) solvation corrections were also used at 0°C. Single point energy refinements were performed at the PBE-D3BJ level of theory with the Ahlrich def2-TZVP basis set (see Supplementary Information for details).

The proposed catalytic cycle for the synthesis of product (R)-3bd begins with the decomposition of the diazo compound 2d by the dirhodium catalyst Rh₂(S-TCPTTL)₄ to afford the dirhodium carbenoid intermediate I (∆G = 0.0 kcal/mol) with the release of molecular nitrogen gas (Fig. 4b). The highly reactive dirhodium carbenoid I undergoes B − H insertion with the incoming o-carborane 1b, forming the major three-member transition state (TS) (II-TS_(R)−B(9), ∆G^‡ = 6.92 kcal/mol), which gives the site selective at B(9)-position and enantioselective preference (R)-enantiomer at the exohedral carbon-stereocenter, which is a carbon-sterocenter adjacent to cage boron of the carborane. This major II-TS_(R)−B(9) leads to the following ground state product complex III (∆G = − 37.5 kcal/mol) wherein the desired product is embedded in the dirhodium catalyst pocket. A second diazo compound 2d releases the major product (R)-3bd (∆G = − 51.1 kcal/mol), as well as molecular nitrogen gas, resulting in regeneration of the dirhodium carbenoid I for the next catalytic cycle. The complete reaction coordinate diagram for this proposed mechanism and the energies are shown in the Supplementary Information (Fig. S8).

Previous reports by Houk and Davies hypothesized that the helical arrangement of the phthalimide ligands of the chiral dirhodium catalyst observed in the ground state as important in determining the selectivities of the C − H insertion process in their studies. The conformational complexity and substantial molecular size of this chiral dirhodium-catalyzed carbenoid B–H insertion of carboranes that were challenging to DFT compute also posed significant difficulties to discover and explain where the origins of selectivity arose within the large transition structure complexes. To address these challenges, we employed a Topographical Proximity Surfaces (TPS) visualization to analyze the steric repulsions that exist in the TSs (Fig. 4c). First, taking the DFT optimized II-TS, the electron isodensity surface of the dirhodium carbenoid complex I was rendered. Then the surface was color-coded to reflect the close steric contact between it and TMS groups of the o-carborane 1b. In this manner, the intensity of the color represents the severity of steric interactions. Hence, this TPS approach can reveal close steric contacts in large, complex transition structures and aid in the rationalization of reaction selectivities.

In the favored major (R)-B(9)-insertion TS (II-TS_(R)−B(9), ∆G^‡ = 6.92 kcal/mol), the dirhodium carbenoid insertion occurs at B(9) position of o-carborane 1b to give the (R)-configuration product at the exohedral carbon-stereocenter adjacent to cage boron of the carborane. The unfavored epimeric dirhodium carbenoid insertion results in the minor (S)-B(9)-insertion TS (II-TS_(S)−B(9), ∆G^‡ = 8.96 kcal/mol, i.e. stereoselectivity of 2.04 kcal/mol), and the unfavored regioisomeric insertion results in the minor (R)-B(8)-insertion TS (II-TS_(R)−B(8), ∆G^‡ = 9.00 kcal/mol, i.e. site-selectivity of 2.08 kcal/mol). These DFT results agree with the experimental site- and enantioselectivity of 2.00 kcal/mol and 2.87 kcal/mol, respectively. The TPS visualization of the major (R)-B(9)-insertion TS (II-TS_(R)−B(9)) reveals a comparatively diminished steric repulsion between TMS groups of the o-carborane 1b and the dirhodium carbenoid complex I (Fig. 4c). This is a result of the o-carborane angle and positioning of the TMS groups into the phthalimide ligand cavity (movie S1). In contrast, the TPSs of the epimeric (S)-B(9)-insertion TS (II-TS_(S)−B(9)) and the regioisomeric (R)-B(8)-insertion TS (II-TS_(R)−B(8)) both show greater steric repulsion of the TMS groups against the phthalimide ligands of the dirhodium carbenoid complex I. In the former, in order to achieve the epimeric insertion of the minor (S)-configuration product, it necessitates the angle and positioning of the o-carborane such that the TMS groups clash into the wall of the phthalimide cavity (II-TS_(S)−B(9), movie S2). Similarly, in the regioisomeric (R)-B(8)-insertion TS (II-TS_(R)−B(8)), the rotation of the o-carborane to achieve insertion at the B(8) position not only results in steric interactions between the TMS groups with the phthalimide ligands, but also with the aryl substituent of the carbene substrate itself (movie S3). These results visually reveal the extent and severity of steric interactions that govern the preference for the favored B–H insertion process by this large and conformationally flexible dirhodium catalyst, Rh₂(S-TCPTTL)₄.

In summary, effective site- and enantioselective B − H insertion reactions have been developed for the first time from the reaction of donor/acceptor carbenes into cage B − H bond of carboranes with chiral rhodium(II) catalyst. This selective B–H functionalization thereby constructs o-, m-, and p-carboranes possessing exohedral carbon-stereocenter, which is adjacent to cage boron of the carborane in excellent site-selectivity (> 50:1 r.r.) and enantioselectivity (99% e.e.) in high yields with broad substrate scope under mild reaction conditions. We also report the first fully quantum mechanically computed transition structures of the B–H insertion process of carboranes involving the complete large and conformationally flexible chiral dirhodium catalyst carbenoids. Gratifyingly, the computed site-selectivity and enantioselectivity (2.08 kcal/mol and 2.04 kcal/mol, respectively) were in good agreement with the experiments (2.00 kcal/mol and 2.87 kcal/mol, respectively). Furthermore, we reveal a tool to visually highlight the structurally subtle, but energetically critical, distribution of the close steric contact in a topographical fashion. This clearly shows the overall topographical shape created by the large and flexible dirhodium catalyst to which the substrate must bind to undergo reaction. This tool may play a significant role in future computational studies involving large catalyst systems. Ultimately, we discovered that the chiral dirhodium carbenoid is capable of this unique and impressive site- and enantioselectivity on an icosahedral cage substrate because the favored (R)-B(9)-insertion TS is able to angle the di-TMS substituted o-carborane into the phthalimide ligand cavity with minimal steric repulsion. This work opens a new way for true site selective transformations of icosahedral complexes and enantioselective functionalization, affording exohedral chirality through the formation of a single, new B–C bond involved in a concerted B–H insertion.

Data availability

The X-ray crystallographic data for structures have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition numbers 2031747, 2085991, 2036998, 2036999, and 2085990 and can be obtained free of charge from https://www.ccdc.cam.ac.uk/structures/. All other data are available in the main text or the Supplementary Information.

Competing interests

The authors declare no competing financial interest.

Author contributions

Conceptualization: P.H.L.; Project administration & supervision: P.H.L. and P.H.-Y.C.; Experimental study: K.L., H.E., T.H.K., and H.C.N.; Computational study: G.A.G.-M., A.O.F., and H.R.W.; Crystallographic analysis: D.K.; Writing – original draft: P.H.L., P.H.-Y.C., K.L., and G.A.G.-M.; Writing – review & editing: P.H.L., P.H.-Y.C., K.L., and G.A.G.-M.

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2021R1A2C3008862 and RS-2023-00271205). PHYC is the Bert and Emelyn Christensen Professor and gratefully acknowledges financial support from the Vicki & Patrick F. Stone family and the computing infrastructure in part provided by the National Science Foundation (CHE-1352663 and NSF Phase-2 CCI, Center for Sustainable Materials Chemistry CHE-1102637). We thank CTK (Chiral Technology Korea) for the chiral HPLC analysis and Mr. Euijae Lee for helpful discussion.

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Site- and enantioselective B−H functionalization of carboranes
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Site- and enantioselective B−H functionalization of carboranes

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