Ligand non-innocence and an unusual σ-bond metathesis step enables catalytic borylation using 9-borabicyclo-[3.3.1]-nonane

Abstract

The metal-catalyzed intermolecular C-H borylation of arenes is an extremely powerful C-H functionalization methodology. However, to date it is effectively restricted to forming organo-boronate esters (Aryl-B(OR)₂) with its application to form other organoboranes rarely explored. Herein, we report a catalytic intermolecular heteroarene C-H borylation method using the commercial hydroborane 9-borabicyclo-[3.3.1]-nonane, (H-BBN)₂. This process is effective for mono- and di-borylation to form a range of heteroaryl-BBN compounds using either NacNacAl or NacNacZn (NacNac = {(2,6-ⁱPr₂C₆H₃)N(CH₃)C}₂CH) based catalysts. Notably, mechanistic studies indicated a highly unusual σ-bond metathesis process between NacNacZn-Aryl and the dimeric hydroborane, with first order kinetics in the hydroborane dimer ((H-BBN)₂). Our calculated metathesis pathway involves ligand non-innocence and addition of both H-BBN units in (H-BBN)₂ to the NacNacZn-heteroaryl complex. This is in contrast to the conventional σ-bond metathesis mechanism using other hydroboranes which invariably proceeds by reaction of one equivalent of a monomeric hydroborane (e.g., H-B(OR)₂) with a M-C unit. Overall, this work demonstrates the potential of extending catalytic arene C-H borylation beyond boronate esters, while highlighting that the σ-bond metathesis reaction can be mechanistically more complex when utilizing dimeric hydroboranes such as (H-BBN)₂.

Fig. 1. (A): Comparison of the current status of catalytic C–H borylation using monomeric H–B(OR)₂ and dimeric (H–BBN)₂. (B): Previous catalyzed C–H zincation and alumination. (C): This work.

Chart 1. Substrate scope for zinc-catalyzed borylation. ^a Yield relative to (H–BBN)₂ using an internal standard. ^b at 100 °C.

Chart 2. Aluminium catalyzed C–H borylation. ^a Yield versus an internal standard. ^b 1.5 equiv. (H–BBN)₂.

Fig. 2. Reaction of 3i/3j with (H–BBN)₂. Bottom, solid-state structures of 3i/3j-(H–BBN), ellipsoids at 50% probability and most hydrogens omitted for clarity. Inset right the formation of compound B also containing a CB₂H core.

Chart 3. Zinc catalyzed diborylation of thiophenes. ^a Yield versus an internal standard. ^b Isolated yield.

Scheme 1. Utilization of thienyl–BBN products. ^a Borylation conditions from Table 1.

Scheme 2. Disparate outcomes from the borylation of 2,5-N-trimethylpyrrole.

Fig. 3. Top, the formation of 11 by metathesis of 10 with (H–BBN)₂ (also forming 3a) or by direct addition of 0.5 equiv. (H–BBN)₂ to 1. Inset, the solid-state structure of 11. Bottom, the disparate outcome from protonolysis of 11.

Fig. 4. Proposed catalytic cycle for C–H borylation.

Scheme 3. Calculated free energies (kcal mol⁻¹) to form the borenium equivalent INT-2B+.

Fig. 5. (a) Computed free energy reaction profile (kcal mol⁻¹) for the catalytic C–H borylation of 2-methyl-thiophene focusing on the σ-bond metathesis phase. (Method: B3PW91(def2-TZVP, D3(BJ), PhCl)//B3PW91(Zn: SDD; S: SDD (d); other atoms: 6-31G**)). (b) Details of key intermediates in the σ-bond metathesis process (distances in Å; inset defines the metallacycle folding angle, ϕ; NacNac, BBN and 2-methyl-thiophene substituents shown in wireframe for clarity).

Scheme 4. Free energies (kcal mol⁻¹) for the protonolysis phase that proceeds via1 with only the highest transition state energy shown. Energies are in kcal mol⁻¹ relative to the zero energy defined in Fig. 5.