Nickel-catalyzed 1,2-dialkenylation of o-carboranes with alkenyl bromides

Abstract

A nickel-catalyzed cross-coupling reaction of o-carboranyl with alkenyl bromides has been developed, affording a series of 1,2-dialkenylated o-carboranes with a broad substrate scope. This reaction provides an efficient and concise strategy for C,C′-dialkenylation of o-carboranes and supplements the transition-metal catalyzed cage B–H functionalization systems.

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Icosahedral carboranes are a class of boron–carbon molecular clusters with characteristic properties, including three-dimensional aromaticity, inherent robustness, high hydrophobicity, and high boron content.^1,2 The carborane derivatives have found wide applications in different fields, ranging from medicine,³ materials,⁴ and coordination/organometallic chemistry⁵ to catalysis.⁶ In recent years, the development of efficient methodologies for the functionalization of carboranes on either C–H^1,7 or B–H⁸ vertices has received increasing research attention and achieved significant progress. A conventional method for cage-C functionalization utilized the acidic nature of cage-CH to generate nucleophilic carbon centers with a strong base, which can subsequently react with electrophiles.^1a Nevertheless, such a synthetic strategy was not practical for alkenylation or arylation of carboranes on the cage C position.

The first synthesis of 1,2-dialkenyl-o-C₂B₁₀H₁₀ was achieved by Cohen and co-workers through the condensation reaction of decaborane with diisopropenylacetylene giving a very low yield (Scheme 1a).⁹ In 1971, Hawthorne and co-workers reported the synthesis of 1,2-diethenylated o-carborane via an elimination reaction of a carboranyl diol at a very high temperature (350 °C) with only one example (Scheme 1b).¹⁰ In 1986, Zakharkin and co-workers reported that treatment of 1,2-Li₂-o-C₂B₁₀H₁₀ with perfluoropropylene produced 1,2-di(perfluoropropylenyl)-o-carborane in moderate yields.¹¹ These reactions suffered from low yields and limited substrate scope. In recent years, our group has established diversified methods for the synthesis of 1-alkenyl-o-carboranes, including the reaction of nickel carborane with alkenes (Scheme 1c),¹² phosphine-catalyzed coupling of o-carborane with electron-deficient alkynes (Scheme 1d)¹³ and light-enabled cage C-alkenylation with unactivated alkenes via a radical process (Scheme 1e).¹⁴ Nevertheless, only mono-alkenylated o-carboranes could be prepared by these methods, although with high efficiency and good compatibility with a wide range of substrates. Compared to feasible cage BH dialkenylations via transition metal catalysis,¹⁵ there is no reported catalytic method for cage C-dialkenylated o-carboranes as of now.

Scheme 1 Cage carbon alkenylation of o-carboranes.

In 2015, a nickel-catalyzed 1,2-diarylation of o-carboranyl with aryl iodides was developed by our group, offering a practical approach for synthesizing C,C′-diarylated o-carboranes with high efficiency.¹⁶ In this connection, we initiated a study to develop a transition metal catalyzed 1,2-dialkenylation of o-carboranes. Herein we present a nickel-enabled cross-coupling of o-carboranyl with alkenyl bromides for the efficient preparation of a variety of 1,2-dialkenyl-o-carboranes.

We commenced our study by screening the reaction temperature for the cross-coupling of 1,2-(MgCl)₂-o-C₂B₁₀H₁₀ with β-bromostyrene (2a) in toluene with NiCl₂ as the catalyst. 1,2-(MgCl)₂-o-C₂B₁₀H₁₀ was prepared in situ by treating 1.0 equiv. of o-carborane with 2.4 equiv. of ⁱPrMgCl in THF at 50 °C for 12 h. With 30 mol% of NiCl₂ in toluene at 120 °C, the desired product 3a was obtained in 94% GC yield (entry 1, Table 1). High temperature was required for such a coupling, while the reaction at 80 °C resulted in a decreased yield of 3a to 81% (entries 2 and 3, Table 1). When the catalyst loading was lowered to 15 mol%, no change was observed in the yield of 3a. But a further decrease to 10 mol% reduced the yield of 3a to 88% (entries 4 and 5, Table 1). Other nickel catalysts (entries 6–9, Table 1) and solvents (entries 10–12, Table 1) were less effective. Accordingly, the conditions shown in entry 4 (Table 1) were considered to be the optimum reaction conditions.

Table 1 Optimization of the reaction conditions^a

Entry	[Ni] (mol%)	Solvent	T [°C]	Yield^b (%)
THF = tetrahydrofuran. Et2O = diethyl ether.a Reactions were conducted on a 0.2 mmol scale of 1a in 2 mL of solvent in a closed flask for 20 h.b GC yield.
1	NiCl2 (30)	Toluene	120	94
2	NiCl2 (30)	Toluene	100	93
3	NiCl2 (30)	Toluene	80	81
4	NiCl2 (15)	Toluene	100	93
5	NiCl2 (10)	Toluene	100	88
6	NiBr2 (15)	Toluene	100	80
7	Ni(PMe3)Cl2 (15)	Toluene	100	24
8	Ni(PPh3)Cl2 (15)	Toluene	100	29
9	Ni(dppe)Cl2 (15)	Toluene	100	61
10	NiCl2 (15)	THF	100	76
11	NiCl2 (15)	Hexane	100	Trace
12	NiCl2 (15)	Et2O	100	Trace

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Subsequently, the substrate scope of this coupling was examined, and the results are shown in Scheme 2. β-Bromostyrenes with various functional groups, including alkyl, methoxyl, thienyl, trifluoromethyl and halides, were well tolerated to afford the corresponding 1,2-dialkenyl-o-carboranes in 28%–85% yields (3a–3s). In general, electron-donating substituents led to higher yields than the corresponding electron-withdrawing ones, regardless of their positions on the phenyl rings. However, for 3d with an ⁱPr group and 3e with a ^tBu group, the lower yields of dialkenylated products might be related to the difficult installation of the second alkenyl group probably due to the steric effect, since monoalkenylated carboranes were observed in the reaction mixture. Harsher conditions, including higher temperature, a larger dose of the catalyst, a longer reaction time, and/or a small amount of THF, could effectively increase the yields of 3d–3g, 3j–3k, 3n–3o and 3r, which bear either a sterically-bulky or electron-withdrawing group. Also, alkyl, alkoxyl and trimethylsilyl bromoalkenes were compatible, giving 3t and 3v–3y in 33%–71% yields, comparable to those of β-bromostyrenes. Moreover, substitution on the α-carbon of bromoalkenes would inhibit such a coupling reaction, comparing 3t with 3u (33% vs. trace) and 3y with 3z (63% vs. 0%). The reason might be ascribed to the increased steric hindrance around the reaction center, which might impede oxidative addition or the subsequent reductive elimination step. Notably, the isolation of 3x as a single isomer confirmed the retention of the E or Z configuration of the alkenyl group in this coupling as the double bond remains intact during the reaction. On the other hand, the coupling of B(9)-phenyl- and B(9,12)-diphenyl-o-carborane worked well to produce the desired products 3aa and 3ab in 63%–66% yields. In addition, the isolated yields remained almost unchanged if the reactions were scaled up by 10 times (3a, 3f and 3l in Scheme 2).

Scheme 2 Synthesis of 1,2-dialkenyl-o-carboranes (isolated yields are presented). ^aGeneral conditions: 1 (0.20 mmol), 2 (0.48 mmol), NiCl₂ (15%), toluene (2.0 mL), 100 °C, 20 h. Isolated yield. ^b NiCl₂ (30%), 130 °C, 72 h. ^c 2.0 mmol scale instead of 0.2 mmol. ^d Tol/THF = 50 : 1.

Compounds 3 were fully characterized using ¹H, ¹³C, and ¹¹B NMR spectroscopy and high-resolution mass spectrometry (HRMS). Their ¹¹B{¹H} NMR spectra exhibited either a 2 : 8 or a 2 : 2 : 6 pattern, consistent with that of 1,2-disubstituted o-carboranes. The signals of cage-carbon atoms were found at about 80 ppm in the ¹³C{¹H} NMR spectra. The molecular structures of 3a, 3j, 3l, 3q, 3r, and 3v were further confirmed by single-crystal X-ray analyses.

To gain some insights into the mechanism, the following control experiments were conducted. No reaction occurred in the absence of NiCl₂, indicating the indispensability of nickel catalysts (Scheme 3a). The yield of 3a remained unaffected in the presence of 1.0 equiv. of 1,1-diphenylethylene as the radical trapping agent, obviating the involvement of a radical pathway (Scheme 3b).¹⁷ The coupling reaction of 1-MgCl-o-C₂B₁₀H₁₁ and 2a gave mono-substituted product 4 in a yield of 48%. Treatment of 4 with 1.2 equiv. of ⁱPrMgCl and subsequent coupling with 2a generated 3a in 75% isolated yield, revealing that such a Kumada-type coupling proceeded in a stepwise manner (Scheme 3c).¹⁸

Scheme 3 Control experiments.

Based on the aforementioned experimental results and literature reports,^16,18 a plausible mechanism is proposed in Scheme 4. The catalytic cycle starts from in situ generation of Ni0 species via the reduction of NiCl₂ by Grignard reagents. Oxidative addition of alkenyl bromides on Ni0 leads to the formation of an [alkenyl-Ni^IIBr(solvent)₂] complex (A). Transmetallation between A and 1,2-(MgCl)₂-o-carborane (B) affords intermediate C, followed by reductive elimination to give 1-alkenyl-2-MgCl-o-carborane (D) and regenerate catalytic Ni0 species. From D, a repeat of this catalytic cycle produces 3a as the final product.

Scheme 4 Proposed mechanism.

In summary, a nickel-catalyzed cross-coupling reaction of o-carboranyl with alkenyl bromides has been developed. Electronic effects are distinct where electron-rich substrates surpass electron-deficient ones. The reaction scales can be properly enlarged with high yields. This reaction demonstrates a broad substrate scope with good compatibility towards various functional groups, enabling the synthesis of a series of C,C′-dialkenylated o-carboranes. This method offers a straightforward and efficient approach for one-step incorporation of two alkenyl functionalities into o-carborane frameworks, providing valuable synthons for the construction of complex structures with potential applications in materials science.

Conflicts of interest

There are no conflicts to declare.

Data availability

Supplementary information (SI): experimental details and characterization data. See DOI: https://doi.org/10.1039/d5dt02451j.

CCDC 2491517–2491522 (3a, 3j, 3l, 3q, 3r and 3v) contain the supplementary crystallographic data for this paper.^19a–f

Acknowledgements

This work was supported by grants from the Research Grants Council of the Hong Kong Special Administrative Region (Project No. 14305424 to J. Z.), the National Natural Science Foundation of China (Project No. 22331005 to Z. X. and 22201238 to J. Z.), and the Shenzhen Science and Technology Program (Project No. KQTD20221101093558015 to Z. X.).

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