Understanding and Expanding Zinc Cation/Amine Frustrated Lewis Pair Catalyzed C–H Borylation

Abstract

[(NacNac)Zn(DMT)][B(C6F5)4], 1, (NacNac = {(2,6- i Pr2H3C6)N(CH3)C}2CH), DMT = N,N-dimethyl-4-toluidine), was synthesized via two routes starting from either (NacNac)ZnEt or (NacNac)ZnH. Complex 1 is an effective (pre)catalyst for the C–H borylation of (hetero)arenes using catecholborane (CatBH) with H2 the only byproduct. The scope included weakly activated substrates such as 2-bromothiophene and benzothiophene. Computational studies elucidated a plausible reaction mechanism that has an overall free energy span of 22.4 kcal/mol (for N-methylindole borylation), consistent with experimental observations. The calculated mechanism starting from 1 proceeds via the displacement of DMT by CatBH to form [(NacNac)Zn(CatBH)]+, D, in which CatBH binds via an oxygen to zinc which makes the boron center much more electrophilic based on the energy of the CatB-based LUMO. Combinations of D and DMT act as a frustrated Lewis pair (FLP) to effect C–H borylation in a stepwise process via an arenium cation that is deprotonated by DMT. Subsequent B–H/[H-DMT]+ dehydrocoupling and displacement from the coordination sphere of zinc of CatBAr by CatBH closes the cycle. The calculations also revealed a possible catalyst decomposition pathway involving hydride transfer from boron to zinc to form (NacNac)ZnH which reacts with CatBH to ultimately form Zn(0). In addition, the key rate-limiting transition states all involve the base, thus fine-tuning of the steric and electronic parameters of the base enabled a further minor enhancement in the C–H borylation activity of the system. Outlining the mechanism for all steps of this FLP-mediated process will facilitate the development of other main group FLP catalysts for C–H borylation and other transformations.

Main Group Catalyzed Arene Borylation: Challenges and Opportunities

“…The scope of this process was found to be affected by the base used and also by the nature of the zinc cation, indicating that varying the activating metal electrophile that binds to CatBH can have a dramatic effect on reactivity. 23,24 In recent work, Wang and co-workers reported the use of the borenium cation 10 (Scheme 6) as the electrophilic activator. 15 10 activated 4-chloro-CatBH 25 to form an electrophile that was highly effective in arene borylation.…”

“…Our recent work utilized this approach in catalytic arene borylation with low coordinate zinc cations calculated to prefer binding to O over the B–H unit (Scheme inset, 7-O vs 7-H ) . Using 10 mol % of compound 8 (Scheme ) as a precatalyst enabled catalytic borylation and an increase in the arene scope relative to [CatB–L] 1+/0 mediated catalytic borylation, with benzothiophene now amenable to C–H borylation . Computational analysis revealed a mechanism initiated by an endergonic displacement of amine NR 3 from zinc by CatBH to form 9 .…”

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

“…Due to its unique chemical features for promoting ligand exchanges, it coordinates into different geometries, resulting in the ubiquitous presence of thousands of proteins and enzymes [123]. This is because of its ability to undergo Lewis activation and nucleophile formation [124]. This catalyst makes it possible to use hydrolytic reactions for DNA cleavage in designing anti-tumour drug activities [125].…”

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

“…Due to its unique chemical features for promoting ligand exchanges, it coordinates into different geometries, resulting in the ubiquitous presence of thousands of proteins and enzymes [ 118 ]. This is because of its ability to undergo Lewis activation and nucleophile formation [ 119 ]. This catalyst makes it possible to use hydrolytic reactions for DNA cleavage in designing anti-tumour drug activities [ 120 ].…”