A Pd-catalyzed route to carborane-fused boron heterocycles

Abstract

Due to the expanding applications of icosahedral carboranes in medicinal and materials chemistry research, their functionalizations have become one of the central themes in boron-rich cluster chemistry. Although several strategies for incorporating nitrogen-containing nucleophiles on a single boron vertex of the icosahedral carboranes (C₂B₁₀H₁₂) have been developed, methods for preparing clusters with vicinal B-N moieties are still lacking. The steric bulk of icosahedral carboranes and disparate electronic and steric nature of the N-containing groups have rendered the vicinal diamination challenging. In this article, we show how a developed Pd-catalyzed process is used to incorporate an array of NH-heterocycles, anilines, and heteroanilines with various electronic and steric profiles onto the vicinal boron vertices of a meta-carborane cluster via sequential or one-pot fashion. Importantly, oxidative cyclizations of the cross-coupling products with indoles and pyrroles appended to boron vertices generate a previously unknown class of all-boron-vertex bound carborane-fused six- and seven-membered ring heterocycles. Photophysical studies of the meta-carborane-fused heterocycles show that these structures can exhibit luminescence with high quantum yields and are amenable to further manipulations.

Fig. 1. (A) Established preparations for o-phenylene diamine structures and synthetically challenging carborane vicinal diamine structures for generating N–B–B–N moieties. (B) In Pd-catalyzed diamination reactions using 9,10-Br₂-m-carborane 1 and heterocycles, the sterically hindered biaryl monophosphine ligand could be detrimental to both coupling steps; triaryl phosphines serve as alternative less bulky ligands and lead to the desired products. (C) Our developed reaction sequence of preparing symmetrical and unsymmetrical diaminated products using the sequential or one-pot cross-coupling protocol using L5 as the optimal ligand. (D) The oxidative cyclization of the double cross-coupling products affords previously unknown all-boron-vertex-bound carborane-fused six- and seven-membered rings.

Fig. 2. Ligand screening for the Pd-catalyzed double cross-coupling reactions between 1 and indole N1. Reaction conditions: 9,10-Br₂-meta-carborane 1 (0.1 mmol, 1.0 equiv.), indole (0.3 mmol, 3 equiv.), 10 mol% Pd(OAc)₂ (0.01 mmol, 10 mol%), 20 mol% ligands (0.02 mmol, 20 mol%) and 1 mL DME at 100 °C for 12 h under a N₂ atmosphere. The yields were determined by GC-MS analysis using decane as an internal standard.

Fig. 3. Substrate scope of Pd-catalyzed symmetrical double cross-coupling reactions. Electron-rich and -poor indoles are compatible under the developed conditions. Reaction conditions: 1 (0.2 mmol, 1 equiv.), heterocycle (0.6 mmol, 3 equiv.), Pd(OAc)₂ (0.02 mmol, 10 mol%), L5 (0.04 mmol, 20 mol%), K₃PO₄ (0.9 mmol, 4.5 equiv.), DME (0.1 M, 2.0 mL), N₂, 100 °C, 12 h. Ellipsoids at 50% probability and all H atoms in single crystal X-ray structures depicted are omitted for clarity. (a) Using t-BuONa as the base and dioxane as the solvent. (b) Using dioxane as the solvent. (c) Using 1,3-bis(dicyclohexylphosphino)propane as the ligand. See the ESI for reaction details.

Fig. 4. Substrate scope of sequential Pd-catalyzed un-symmetrical double cross-coupling reactions. See the ESI for the reaction details. All H atoms in single crystal X-ray structures depicted are omitted for clarity.

Fig. 5. Substrate scope of one-pot Pd-catalyzed un-symmetrical double cross-coupling reactions. See the ESI for the reaction details. All H atoms in single crystal X-ray structures depicted are omitted for clarity.

Fig. 6. The developed protocols for the synthesis of all-boron-vertex-bound meta-carborane-fused heterocycles. (A) In the presence of I₂, six- and seven-membered carborane-fused heterocycles are generated. (B) Different angles of view of the X-ray single crystal structure of 53, top and side views are provided. (C) Different angles of view of the X-ray single crystal structure of 60, top and side views are provided. (D) By using CAN, a dinitro-substituted six-membered heterocycle was obtained. All H atoms in single crystal X-ray structures depicted are omitted for clarity.

Fig. 7. Electronic absorption (dashed line) and emission spectra (solid line, excitation at 310 nm) in CH₂Cl₂ solution (10⁻⁵ M) at room temperature in air, for compounds: (A) 12a and its corresponding oxidative cyclization product 56; (B) 42a and corresponding oxidative cyclization product 58. Photo insets are DCM solutions of 12a, 56, 42a and 58 (10⁻⁵ M, irradiated with UV light, λ_exc = 365 nm).