Readily accessed cobalt pre‐catalysts with N‐heterocyclic carbene ligands catalyze the Suzuki cross‐coupling of aryl chlorides and bromides with alkyllithium‐activated arylboronic pinacolate esters. Preliminary mechanistic studies indicate that the cobalt species is reduced to Co0 during the reaction.

Intrigued by recent reports on the surprisingly excellent activity of a range of cobalt, iron, copper and nickelbased catalysts in the Suzuki biaryl cross-coupling of simple arylboronic acids with aryl halides, we undertook a reexamination of the syntheses of representative examples of the reported pre-catalysts and their application to the catalytic reaction. A reported PNP-Fe pincer complex, in our hands, proved to be a mixture of starting materials; a mono-Schiff base cobalt complex in fact the bis-ligated adduct and a monomeric copper (II) PNP pincer complex a di-or oligomeric copper(I) species. In our hands, neither these complexes, nor any other of the selected pre-catalysts investigated, showed any activity in a Suzuki cross-coupling reaction of an electronically-activated aryl bromide with phenyl boronic acid. Meanwhile, switching the nucleophile to the BuLi-activated phenyl boronic pinacol ester gave some promising activity with cobalt pre-catalysts.

Readily accessed cobalt pre-catalysts with N-heterocyclic carbene ligands catalyze the Suzuki cross-coupling of aryl chlorides and bromides with alkyllithium-activated arylboronic pinacolate esters.P reliminary mechanistic studies indicate that the cobalt species is reduced to Co 0 during the reaction.The palladium-catalyzed cross-coupling of organoboronic acids or esters with organic halides or related substrates-the Suzuki reaction-is ap owerful and very widely exploited method for the formation of biaryl compounds (Scheme 1). [1] This reaction is used commercially for the production of arange of materials,including the sartan class of angiotensin inhibitors for the treatment of hypertension (e.g. Lorsartan) and Boscalid, abroad-spectrum agrochemical fungicide.[2]While palladium-based catalysts are ubiquitous in Suzuki cross-coupling reactions,there is agrowing impetus to replace them with more sustainable alternatives based on earthabundant metals (EAM). This is not only because of the fact that palladium, like all platinum-group metals (PGMs), is scarce and expensive,b ut also because of the relatively high toxicity of PGMs;asac onsequence of this toxicity there are strict regulations in place for the removal of PGMs to the low ppm level from active pharmaceutical intermediates.[3] Of the EAM alternatives to palladium for Suzuki biaryl coupling, first-row transition metals are particularly attractive,w ith nickel-based catalysts being the most well developed to date. [4,5] Iron-catalyzed Suzuki cross-coupling can be performed between avariety of organic halides and organoboron reagents, [6] but simple biaryl bond formation remains elusive and challenging. [6a, 7, 8] Recently,C hirik and co-workers reported early results in the coupling of aryl triflates with arylboron pinacol esters by using ac obalt PNP-pincer-based catalyst.[9] We now report the cross-coupling of aryl chlorides and bromides with activated arylboronic pinacol esters, [10,11] using simple cobalt catalysts prepared in situ from commercially available precursors.Ther esults shown in Table 1s ummarize selected [12] optimization studies using 4-chorotoluene and the activated phenylboronic ester 1a, [6b,c,e, 8] catalyzed by species formed in situ from cobalt(II) chloride with ar ange of different ligands and ligand precursors.No reaction was observed in the absence of added ligand (Table 1, entry 1) and little or no product 2a was obtained when mono,b i-, or tridentate phosphine ligands were tested Scheme 1. Palladium-catalyzed Suzuki biaryl coupling and selected products.