Mild Cobalt‐Catalyzed Negishi Cross‐Couplings of (Hetero)arylzinc Reagents with (Hetero)aryl Halides

Abstract

A catalytic system consisting of CoCl2 ⋅2 LiCl (5 mol %) and HCO2 Na (50 mol %) enables the cross-coupling of various N-heterocyclic chlorides and bromides as well as aromatic halogenated ketones with various electron-rich and -poor arylzinc reagents. The reactions reached full conversion within a few hours at 25 °C.

Decarboxylative Negishi Coupling of Redox‐Active Aliphatic Esters by Cobalt Catalysis

“…[10] To verify this possibility,w es ubjected the cyclopropyl-substituted substrate 1b to the reaction, and ar ing-opening arylation product 85 was produced (Scheme 2a). Thei nvolvement of radical intermediates in cobalt-catalyzed coupling reactions has been suggested previously.…”

“…The success of an in situ activation protocol and the facile synthesis of the drug molecule (AE)-preclamol highlight the synthetic potential of this method. [8] Inspired by these elegant studies,w e reasoned that al ow-valent cobalt catalyst could also donate an electron to the redox-active ester, [9] thereby triggering alkyl radical formation and af ollow-up cross-coupling reaction.Cobalt, as an earth-abundant and low-toxic first-row transition metal, has been previously identified as an attrac-tive catalyst enabling the effective coupling of aryl, [10] alkenyl, [11] and alkynyl halides [12] (or their pseudohalides) with organozinc compounds (Figure 1a). [1] While organohalides have enjoyed as uccess as the electrophilic coupling partners,r ecent years have witnessed ag rowing interest in the use of aliphatic carboxylic acids (or their derivatives) as alkyl halide surrogates in such reactions.…”

“…Cobalt, as an earth-abundant and low-toxic first-row transition metal, has been previously identified as an attrac-tive catalyst enabling the effective coupling of aryl, [10] alkenyl, [11] and alkynyl halides [12] (or their pseudohalides) with organozinc compounds (Figure 1a). Nevertheless,t he use of unactivated alkyl electrophiles [13] in cobalt-catalyzed Negishi coupling reactions is only recent.…”

“…[15] Theu se of the tetrachloro-substituted NHPI ester TCNHP was also effective,b ut resulted in lower yield (44 %). Besides p-toluenesulfonyl (Ts), other commonly encountered amino protecting groups,s uch as benzoyl (Bz;p roducts 4,8,10,12), carboxybenzyl (Cbz; products 5, 13), and tert-butoxycarbonyl (Boc;products 6, 26) were compatible.O ther heterocyclic (products 24-27)a nd cyclic secondary carboxylic acids (product 28), including those bearing an a-heteroatom (products 26, 27), were all viable substrates.I nterestingly,N -protected phenylalanine could also be used to deliver the corresponding product 29. Anumber of ligands were screened, but no improvement in the yield was observed.…”

Decarboxylative Negishi Coupling of Redox‐Active Aliphatic Esters by Cobalt Catalysis

“…Diaryl zinc reagents bearing various functional groups were well tolerated, providing the expected decarboxylative arylation products 7-21 in good yields.D iheteroaryl zinc compounds were also applicable (products 22, 23). Besides p-toluenesulfonyl (Ts), other commonly encountered amino protecting groups,s uch as benzoyl (Bz;p roducts 4,8,10,12), carboxybenzyl (Cbz; products 5, 13), and tert-butoxycarbonyl (Boc;products 6, 26) were compatible.O ther heterocyclic (products 24-27)a nd cyclic secondary carboxylic acids (product 28), including those bearing an a-heteroatom (products 26, 27), were all viable substrates.I nterestingly,N -protected phenylalanine could also be used to deliver the corresponding product 29. Primary alkyl carboxylic acids yielded the desired products 30-34 as well.…”