Palladium catalyzed regioselective mono-alkenylation of o-carboranes via Heck type coupling reaction of a cage B–H bond

Abstract

A regioselective mono-alkenylation of o-carboranes on B(8) and B(9) via palladium catalyzed Heck type coupling of a cage B–H bond has been developed, and kinds of B(8)/B(9)-alkenyl-o-carboranes decorated with active groups have been synthesized with moderate yield as well as good regioselectivity. A Pd^II catalyzed electrophilic B–H activation mechanism was also proposed.

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Carboranes with icosahedron and three-dimensional aromaticity are an important construction unit featuring in medicinal chemistry,¹ supramolecular² and coordination chemistry.³ Synthesis of carborane derivatives with diverse functional groups would offer a platform to examine their coveted properties and applications.⁴ In particular, introducing aromatic or conjugated groups into the cage carbon of carboranes to extend the π-conjugated system to examine their light-emitting or nonlinear optical properties has received much attention.⁵ In contrast to the well-established methodologies for carbon functionalization of carboranes,⁶ methods for regioselective boron functionalization have been difficult as the slight difference in reactivity of the not equally full 10 cage B–H bonds had led their functionalization being more complicated.⁷ Therefore, developing new methods for the regioselective boron derivatization is eagerly desired. Except the typical methods involving boron-halogenation,⁸ recently, using transition metal catalyzed B–H activation for regioselective functionalization of o-carborane has been a prominent strategy but a challenging subject.^9,7b

For o-carboranes, molecular orbitals calculation demonstrate B(9,12) possess slight higher negative charge density than that of B(8,10), which led the electrophilic reaction of B(9,12) prior to that of B(8,10).¹⁰ Base on this characteristic, we consider that distinguishing the slight difference in reactivity might reliable by transition metal catalyzed electrophilic B–H activation, and the congested environment of o-carborane would restraint the forming of poly-substituted o-carboranes to achieve its regioselective mono-functionalization. With this assumption, we recently disclosed a regioselective mono-arylation at B(8) and B(9) of o-carboranes with iodobenzenes.^9e With our continued research interest in boron cluster chemistry,¹¹ herein, we present a regioselective mono-alkenylation of o-carborane via Heck type coupling of cage B–H bond.

In the beginning of our research, 1,2-Me₂-o-carborane (1a) and styrene were selected to examine conditions. To our delight, when the reaction was conducted with 10 mol% of Pd(OAc)₂ and 2 equivalent of AgOAc in 1,2-dichloroethane at 80 °C for 48 h, the desired coupling product was obtained with 39% yield (Table 1, entry 1). Further investigation demonstrated THF was a superior medium for this coupling (entries 2–4), and the expected product was afforded in 63% yield with 77% conversion ratio of 1a, and the regioselectivity at B(8) and B(9) with a ratio of about 1 : 1, meanwhile, the mono-alkenylation at B(8) and B(9) position were confirmed by the chemical shift of boron in ¹¹B NMR. Other silver and copper salts were then examined and displayed lower efficiency than that of AgOAc (entries 5–10). Additionally, palladium source were also screened, which behaved lower catalytic efficiency (entries 11–13).

Table 1 Palladium catalyzed alkenylation of 1,2-Me₂-o-carborane with styrene^a

Entry	Catalyst	Additive	Solvent	Yield^b (%)
a All reactions were carried on 0.250 mmol 1a, 0.025 mmol catalyst, 0.500 mmol styrene, 0.500 mmol additive and 1 mL solvent at 80 °C for 48 h under argon atmosphere. b Isolated yield, and the ratio of B(8) and B(9) isomers was determined based on ^1H NMR. c DCE: 1,2-dichloroethane. d The conversion ratio was calculated based on the recovered 1a.
1	Pd(OAc)2	AgOAc	DCE^c	39
2	Pd(OAc)2	AgOAc	Toluene	51
3	Pd(OAc)2	AgOAc	CH3CN	28
4	Pd(OAc)2	AgOAc	THF	63^d
5	Pd(OAc)2	AgBF4	THF	6
6	Pd(OAc)2	AgOTf	THF	7
7	Pd(OAc)2	Ag3PO4	THF	10
8	Pd(OAc)2	Ag2O	THF	—
9	Pd(OAc)2	Cu(OAc)2	THF	16
10	Pd(OAc)2	CuO	THF	—
11	Pd(PPh3)2Cl2	AgOAc	THF	54
12	Pd2(dba)3	AgOAc	THF	—
13	Pd(dppf)2Cl2	AgOAc	THF	29

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Based on the optimized conditions (Table 1, entry 4), the scope of this transformation was explored and the results were summarized in Table 2. We can see that both C_cage-mono-substituted and C_cage-disubstituted o-carborane were compatible with this reaction, and generated the expected products with moderate yields as well as good regioselectivity. However, unsubstituted o-carborane created an intricate result. The regioselectivity was uncontrollable and gave a complicated alkenylation products including the desired B(8) and B(9) isomers. This result demonstrated the substituents at C_cage play an important role in control the regioselectivity of electrophilic reaction of B–H bonds, which might ascribed to the changed charge distribution among boron atoms induced by the substituents on cage carbons.¹²

Table 2 Palladium catalyzed regioselective mono-alkenylation of o-carboranes with styrene^a,b

a All reactions were carried on 0.25 mmol scale in 1 mL THF at 80 °C for 48 h under argon atmosphere, and the conversion ratio was calculated based on the recovered o-carboranes. b Isolated yield, the ratio of B(8) and B(9) isomers was determined based on ¹H NMR and the conversion ratio of o-carborane are given in parentheses.

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Further investigation indicated this regioselective mono-alkenylation has a good applicability to styrenes decorated with kinds of functional groups. However, styrenes either with electron donating groups or electron withdrawing groups were all not active enough for this transformation, and only attained moderate conversion ratio and gave the corresponding product with lower to moderate yields (2f–2n, Table 3). On the other hand, aliphatic alkenes such as ethyl vinyl ketone and vinyl acetate were also compatible with this reaction, and gave the desired products with moderate yields (2o–2p). Although the efficiency of the reaction is not well enough, this is the first direct approach to regioselective mono-alkenylation of o-carobranes at B(8) and B(9).¹³

Table 3 Palladium catalyzed regioselective mono-alkenylation of 1,2-Me₂-o-carborane with olefins^a,b

a All reactions were carried on 0.25 mmol scale in 1 mL THF at 80 °C for 48 h under argon atmosphere. b Isolated yield, the ratio of B(8) and B(9) isomers determined based on ¹H NMR and the conversion ratio of o-carborane are given in parentheses.

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Based on the experiment results, a possible mechanism was proposed as shown in Scheme 1. The electrophilic reaction of B–H bond to Pd(II) to form intermediate I, and the regioselectivity was determined in this step as the electrophilic reaction of B(9,12) showed slight prior to that of B(8,10). Then, double bond of olefin inserted into B–Pd bond to give II, after β-H elimination to generate alkenylation product and release Pd(0). At last, oxidation of Pd(0) to Pd(II) by Ag(I) regenerate the active catalyst. The mono-alkenylation might be ascribed to the steric hindrance of alkenyl on boron to hinder secondary alkenylation by forming transition state II as we previously discussed.^14,9e

Scheme 1 Plausible mechanism for the Pd-catalyzed regioselective mono-alkenylation of o-carboranes.

Conclusions

In conclusion, a direct regioselective mono-alkenylation of o-carboranes via palladium catalyzed electrophilic B–H activation/Heck coupling process was developed. A series of B(8)/B(9)-alkenyl-o-carboranes anchored with diverse functional groups were synthesized with moderate yields as well as good regioselectivity. Additionally, the crucial role of substituents on cage carbon in controlling the regioselectivity was disclosed, which would be useful for designation of other coupling reactions selective on B(8) and B(9).

Acknowledgements

This work is supported by Scientific Research Fund of Sichuan Provincial Education Department (No. 13TD0022), Open Project of State Key Laboratory Cultivation Base for Nonmetal Composites and Functional Materials (No. 11zxfk26, 13zxfk06), and Doctoral Research Foundation of Southwest University of Science and Technology (13zx7134).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Complete characterization data. See DOI: 10.1039/c5ra18555f

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