Towards Iron-Catalysed Suzuki Biaryl Cross-Coupling: Unusual Reactivity of 2-Halobenzyl Halides

Abstract

The reaction of 2-halobenzyl halides with the borate anion Li[(Ph)(t-Bu)Bpin] leads not only to the expected arylation at the benzyl position, but also to some Suzuki biaryl cross-coupling. Preliminary mechanistic investigations hint towards the intermediacy of benzyl iron intermediates that can either: (a) directly cross-couple with the aryl boron reagent to give observed monoarylated species, or (b) undergo oxidative addition of the aryl halide to generate the diarylated species on reaction with the boron-based nucleophile.

Iron-catalysed substrate-directed Suzuki biaryl cross-coupling

“…Indeed, to the best of our knowledge, the only example of a Suzuki biaryl cross-coupling reaction that occurs under mild conditions 30 is obtained in the coupling of 2-halobenzyl halides with the activated boronic ester 1a, which gives the expected benzylarylated product 2 along with some of the biaryl coupled-side product 3. 31 We speculated that the biaryl bond-formation in this case may be due to the substrate 'directing' the activation of the aryl-X bond at the iron centre, as has been observed previously in the olefinassisted alkylation of aryl chlorides. 32 However, aryl halides with classic ortho-directing groups based on tertiary amine, ether, ester, carbamate or imine functions all failed to give the desired cross-coupling.…”

“…32 However, aryl halides with classic ortho-directing groups based on tertiary amine, ether, ester, carbamate or imine functions all failed to give the desired cross-coupling. 31 We now report our preliminary findings into the arylation of aryl chloride substrates with Npyrrole amide and related directing groups (4, Figure 1…”

Cobalt‐Catalyzed Suzuki Biaryl Coupling of Aryl Halides

“…Of the EAM alternatives to palladium for Suzuki biaryl coupling, first‐row transition metals are particularly attractive, with nickel‐based catalysts being the most well developed to date . Iron‐catalyzed Suzuki cross‐coupling can be performed between a variety of organic halides and organoboron reagents, but simple biaryl bond formation remains elusive and challenging . Recently, Chirik and co‐workers reported early results in the coupling of aryl triflates with arylboron pinacol esters by using a cobalt PNP‐pincer‐based catalyst .…”

“…The results shown in Table summarize selected optimization studies using 4‐chorotoluene and the activated phenylboronic ester 1 a ,,, catalyzed by species formed in situ from cobalt(II) chloride with a range of different ligands and ligand precursors.…”

One-Pot Synthesis and Conformational Analysis of Six-Membered Cyclic Iodonium Salts

“…In modification of a reported procedure, [18] o-Iodobenzylalcohol (5a, 1.87 g, 8.00 mmol) was dissolved in dry DCM (40 mL) and SOCl 2 (0.73 mL, 1.19 g, 10.0 mmol, 1.25 eq.) was added dropwise at 0 °C.…”