Iridium-Catalyzed Borylation of Primary Benzylic C–H Bonds without a Directing Group: Scope, Mechanism, and Origins of Selectivity

Abstract

Primary benzylic boronate esters are useful intermediates in organic synthesis, but these reagents cannot be prepared by hydroboration. The benzylic C-H borylation of methylarenes would be a method to form these products, but such reactions without neat methylarene or a directing group are unknown. We report an approach to divert the borylation of methylarenes from aromatic positions to benzylic positions with a silylborane as reagent and a new iridium catalyst containing an electron-deficient phenanthroline as ligand. This system forms benzylic boronate esters selectively over the corresponding aryl boronate esters. An Ir diboryl monosilyl complex ligated by the phenanthroline was isolated and determined to be the resting state of the catalyst. Mechanistic studies show that this complex is kinetically competent to be an intermediate in the catalytic process. Kinetic studies of benzylic and aryl C-H borylation catalyzed by various Ir complexes show that the rate of aryl C-H borylation decreases with decreasing electron density at the metal center of the Ir catalyst, but that the rate of benzylic C-H borylation is less sensitive to the degree of electron density at the metal center of the Ir catalyst. Kinetic and computational studies suggest that the two borylation reactions respond differently to the degree of electron density at the metal center because they occur with different turnover-limiting steps. The turnover-limiting step in the borylation of aryl C-H bonds is known to be C-H oxidative addition, but the turnover-limiting step of the borylation of benzylic C-H bonds appears to be an isomerization prior to C-B reductive elimination.

Chemoselective single-site Earth-abundant metal catalysts at metal–organic framework nodes

“…At 0.2 mol% Co loading, UiO-Co afforded secondary and tertiary benzylic boronate esters from ethylbenzene and isopropryl benzene, respectively, in 100% conversion, and the selectivities for the benzylic products over the aryl products were ∼4:1 (entries 12–13, Table 1). These results contrast with analogous reactions reported with a chemoselective homogeneous iridium catalyst that is active for borylation of only primary benzylic C−H bonds33.…”

C–H Borylation by Platinum Catalysis

“…48 Selective borylation at the benzylic position was possible with an iridium/phenanthroline system when silylborane was used as the borylating agent to deliver 10a. 47 In contrast, the robust Pt catalyst developed in the current study was found to be insensitive to the steric hindrance suffered by the other systems to allow for the exclusive CH borylation of 9 at its 3-position to provide 10b. The current platinum-catalyzed borylation was found to be amenable to scale up, as exemplified by the gram-scale synthesis of 3k, which could be used as a versatile building block for the introduction of different groups (Scheme 6).…”

Ionic Liquids: Recent Advances and Applications in Boron Chemistry

“…Direct borylation of arenes, alkenes, and alkanes to form the corresponding boronic acids or boronates has been developed as one of the most fundamental methodologies in modern organic synthesis, particularly when the products are important raw materials for cross‐coupling reactions in forming new C–C bonds . Catalysts based on iridium complexes, such as [Ir(µ‐X)(cod)] 2 /dtbpy (cod = 1,5‐cyclooctadiene, dtbpy = 4,4′‐di‐ t Bu‐2,2′‐bipyridine, X = Cl, OMe), have demonstrated high performance in direct borylation reactions.…”