meta-Selective C–H Borylation of Benzamides and Pyridines by an Iridium–Lewis Acid Bifunctional Catalyst

Abstract

We report herein the iridium-catalyzed meta-selective C–H borylation of benzamides by using a newly designed 2,2′-bipyridine (bpy) ligand bearing an alkylaluminum biphenoxide moiety. We also demonstrate the iridium-catalyzed C3-selective C–H borylation of pyridine with a 1,10-phenanthroline (Phen) ligand bearing an alkylborane moiety. It is proposed that the Lewis acid–base interaction between the Lewis acid moiety and the aminocarbonyl group or the sp2-hybridized nitrogen atom accelerates the reaction and controls the site-selectivity.

Iridium‐Catalysed C−H Borylation of Heteroarenes: Balancing Steric and Electronic Regiocontrol

“…As with inner-sphere direction, a variety of ingenious ligands have been described that enable selective borylation at more remote meta and para positions. [80][81][82][83][84][85][86] An alternative strategy has been to design systems that create sterically welldefined environments that limit accessibility of the substrate to the catalyst (Scheme 7). For example, para CÀH borylation of aromatic esters and amides can be obtained using cooperative Ir/Al catalysis in which substrate complexation with bulky Lewis acids such as methylaluminum bis(2,6-ditert-butyl-4-methylphenoxide) (MAD) 54 limits access to the ortho and meta positions (Scheme 7 a).…”

“…Interestingly, as shown by this example, a C-2 substituent does not seem to block complexation, giving selective access to 2,5-disubstituted pyridine products (Scheme 25 e). [86] The azinyl nitrogen can also coordinate directly to the Ir metal centre in inner-sphere systems enabling the selective borylation of pendant arene substituents (Scheme 26). Similar directed C À H activation processes of 2-aryl pyridines are common with other metal catalysts, such as Ru.…”

Recent advances in Cu-catalyzed C(sp3)–Si and C(sp3)–B bond formation

“…Straightforward methods for their synthesis involve the copper-catalyzed addition of organoboron compounds to alkynes, alkenes, and unsaturated carbonyl compounds, as well as the nucleophilic borylation of alkyl or aryl halides. While there are reports on the formation of C-B bonds in the presence of NHC complexes [87] with Au [88], Pd [89], Pt [90], and Ir [91] catalysts, the focus here is on Cu-catalyzed reactions. Enantioselective processes have also been studied due to applications of medicinal interest involving optically active organoboron derivatives and their intermediacy as precursors to other functional groups, such as nonracemic alcohols.…”

Catalyst-enabled Site-selectivity in the Iridium-catalyzed C–H Borylation of Arenes

“…More recently, Nakao and co-workers have developed a method for the meta-selective CH borylation of benzamides using 2,2¤-bipyridine ligand L7, which bears an alkylaluminum biphenoxide moiety (Figure 11). 39 The authors postulated that the reaction probably proceeds via a Lewis-acid-base pair formed between the Lewis-acidic aluminum center in L6 and a Lewis-basic functionality of the substrates (Figure 11a). For example, N,N-diethylbenzamide undergoes this CH borylation reaction with exclusive meta-selectivity under the applied conditions.…”