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

Abstract

Ac obalt-catalyzed decarboxylative Negishi coupling reaction of redox-active aliphatic esters with organozinc reagents was developed. The method enabled efficient alkylaryl, alkyl-alkenyl, and alkyl-alkynyl coupling reactions under mild reaction conditions with no external ligand or additive needed. 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. Mechanistic studies indicated that aradical mechanism is involved.Transition-metal-catalyzed cross-coupling reactions to forge C À Cb onds are of vital importance in modern organic synthesis. [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. [2] Advantages are apparent not only in the wide availability of carboxylic acids,b ut also in that alkyl halides are typically unstable,c hallenging to prepare,a nd undergo oxidative addition to transition metals with difficulty.B y activating the carboxylic acid to the corresponding redoxactive ester,s ingle-electron-transfer reduction is feasible to generate an alkyl radical through the extrusion of CO 2 .T his radical-generation process has been involved in diverse carbon-carbon and carbon-heteroatom bond forming reactions based on single photocatalytic systems [3] or dual catalytic systems [4] combining photoredox catalysis with transitionmetal catalysis. [5] Advances by the Baran research group showed that low-valent first-row transition metals,i ncluding nickel [6] and iron, [6h,g, 7] were also effective in abroad range of decarboxylative cross-coupling reactions without the need for light irradiation. Very recently,acopper-catalyzed decarboxylative radical silylation of redox-active aliphatic esters was also developed. [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). Nevertheless,t he use of unactivated alkyl electrophiles [13] in cobalt-catalyzed Negishi coupling reactions is only recent. [14] In 2015, Knochel and co-workers reported an elegant cobalt-catalyzed crosscoupling reaction of (hetero)aryl zinc reagents with primary and secondary alkyl iodides;a lkyl bromides were also applicable but with lower efficiency. [14a] We report herein ac obalt-catalyzed decarboxylative Negishi coupling of activated aliphatic carboxylic acids under mild reaction conditions ( Figure 1b). Ther eaction allowed the synthesis of ab road range of alkylated arenes,a lkenes,a nd alkynes by reaction...

Water-Dispersible, Magnetically Recyclable Heterogeneous Cobalt Catalyst for C–C and C–N Cross-Coupling Reactions in Aqueous Media

“…Lately, the use of cobalt has emerged as an alternative. − In the past decade, a number of Co-catalyzed systems have been reported for C–C and C–N cross-coupling reactions, such as mTEG-CS-Co-Schiff-base, cobalt-bisoxazolines, a mono (NHC) dicobalt complex [(IPr)­(Co 2 )­Co­(μ–η: 2 η 2 -HCCPh)­Co­(CO) 3 ], graphene oxide-immobilized cobalt Schiff base complexes (CoASGO), P4VP-CoCl 2 , or Fe 3 O 4 @PEG/Cu–Co …”