Borenium-Ion-Catalyzed C–H Borylation of Arenes

Abstract

Non-metal-catalyzed C−H borylation of arenes represents a sustainable and environment-friendly approach for the functionalization of arenes. Despite its promise as an alternative to traditional transition-metal systems, its substrate scope is generally limited to electron-rich arenes, thus hindering its application in organic synthesis. Herein, we report the development of a borenium-ion catalyst which can borylate unactivated arenes under ambient conditions with 4-chlorocatecholborane (HBcat Cl ) as borylation reagent. This metal-free catalytic system is suitable for the borylation of C−H bonds in sterically encumbered positions, which has been a challenging task for transition-metal systems. Additionally, this catalytic system allows para-selective one-pot borylation of phenols, which has not been achieved by using transition-metal systems. Our mechanistic investigations and computational studies support a synergistic activation of the H−Bcat Cl bond by the arene substrate and the borenium-ion catalyst. This generates a Wheland intermediate and a neutral hydroborane species and is followed by deprotonation of the Wheland intermediate with the hydroborane species. The latter step of C−H bond cleavage is likely the rate-limiting step.

Arene C–H borylation strategy enabled by a non-classical boron cluster-based electrophile

“…and pentamethylbenzene were examined. These substrates also showed good reactivity and the reactions did not give any undesirable side products (20)(21)(22)(23), likely due to the low reaction temperature insufficient to promote alkyl shifts. It should be noted that direct C-H borylation of these sterically hindered multi-alkylbenzenes is challenging and hardly be obtained at room temperature by other methods 21 .…”

“…However, the steric control can also limit the scope of alkylbenzenes because the catalyst cannot access sterically hindered C–H bonds, notably those ortho to alkyl groups. Consequently, transition-metal catalyzed borylation of sterically hindered arenes such as mesitylene where all aromatic C–H bonds are ortho to alkyls has been limited 21 , 22 . An exceptional example was reported by Chatani et al utilizing an NHC-ligated platinum catalyst, [(ICy)Pt(dvtms)] (ICy = 1,3-dicyclohexylimidazol-2-ylidene, dvtms = divinyltetramethyldisiloxane) where sterically encumbered alkylbenzenes such as mesitylene could be borylated to give corresponding aryl boronic esters 21 .…”

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

“…A highly electrophilic [(NacNac)­Zn] + derivative is able to bind catecholborane (CatBH) and activate it to a greater extent (based on the relative CatB-based LUMO energies) than when using [(NHC)­ZnR] + electrophiles. This leads to an expanded substrate scope for catalytic C–H borylation, with this FLP-catalyzed borylation being the first such process able to borylate weakly activated heteroarenes such as 2-bromothiophene and benzothiophene . The robust and well-defined nature of the [(NacNac)­Zn­(DMT)] + precatalyst enabled detailed computational analysis which indicated that an endergonic, but kinetically accessible, displacement of DMT by CatBH at zinc is essential to get on cycle.…”

“…This leads to an expanded substrate scope for catalytic C–H borylation, with this FLP-catalyzed borylation being the first such process able to borylate weakly activated heteroarenes such as 2-bromothiophene and benzothiophene. 30 The robust and well-defined nature of the [(NacNac)Zn(DMT)] + precatalyst enabled detailed computational analysis which indicated that an endergonic, but kinetically accessible, displacement of DMT by CatBH at zinc is essential to get on cycle. This formed an adduct containing a short Zn···O (CatBH) interaction and a strongly activated CatBH moiety that can be viewed as a borenium cation equivalent.…”

Transition Metal‐Free Aromatic C−H, C−N, C−S and C−O Borylation

“…Very recently, a breakthrough example was reported by Wang and co‐workers, who achieved a borenium‐ion‐catalyzed C−H borylation of unactivated arenes and phenols with 4‐chlorocatecholborane (HBcat Cl ) as the borylating agent under ambient conditions (Scheme 5). [22] This metal‐free catalytic system is suitable for the borylation of C−H bonds in sterically encumbered positions and para position of phenols, which has been a challenging task for transition‐metal systems. Mechanistically, a synergistic activation of the H−Bcat Cl bond by the arene substrate and the (NHC)‐stabilized o ‐carboranyl‐substituted borenium‐ion catalyst generates a Wheland intermediate and a neutral hydroborane species.…”