Co–Mabiq Flies Solo: Light-Driven Markovnikov-Selective C- and N-Alkylation of Indoles and Indazoles without a Cocatalyst

Abstract

Indoles and indazoles are common moieties in pharmaceuticals and naturally occurring bioactive compounds. The development of light-driven methods using earth-abundant transition-metal catalysts offers an attractive route for functionalization of such compounds. Herein, we report a visible-light-induced method for the C3- and N-alkylation of indoles and indazoles with styrenes, catalyzed by Co complexes based on the macrocyclic Mabiq ligand (Mabiq = 2–4:6–8-bis­(3,3,4,4-tetra­methyl­dihydro­pyrrolo)-10–15-(2,2′-biquinazolino)-[15]-1,3,5,8,10,14-hexaene-1,3,7,9,11,14-N6). The photochemical behavior of two CoIII catalysts was examined: Co­(Mabiq)­Cl2 and the newly synthesized Co­(MabiqBr)­Cl2, which contains the Br-modified ligand. Both complexes undergo visible-light-induced homolysis that is significant to their activity but exhibit differences in reactivity. The alkylation reactions are regioselective, furnishing the alkylated indole and indazole products in a Markovnikov fashion with excellent yields of up to 96% across a broad range of substrates. Notably, in contrast to dual-transition-metal and photoredox-catalyzed cross-coupling reactions, our studies reveal that the Co complex plays a dual roleas a photosensitizer and catalytically active metal center with the Mabiq ligand offering regiocontrol.

Light-Driven Cobalt Hydride Catalyzed Hydroarylation of Styrenes

“…The metal hydride could then add a hydrogen atom to the styrene, generating the benzylic radical, which would selectively couple with the radical anion of the cyanoarene, produced via single-electron reduction. This combination of two distinctive modes of catalysis would diversify recent reports of dual MHAT/photoredox catalysis, which had been limited to hydrogenation, isomerization, Giese, or radical polar crossover reactions …”

Further Studies of CoIII(TIM) Mono‐Alkynyl and Bis‐Alkynyl Complexes

“…Also being explored are new synthetic pathways such as the Hagihara coupling (Cu(I)/base catalyzed) that found success in the synthesis of cobalamin acetylide complexes [18] . Our continuing efforts will contribute to organometallic chemistry of Co macrocycles, where notable recent results include photocatalytic C‐ and N‐a lkylation of indoles [19] and ring‐opening copolymerization of CO 2 and propylene oxide [20] …”

“…Also being explored are new synthetic pathways such as the Hagihara coupling (Cu(I)/base catalyzed) that found success in the synthesis of cobalamin acetylide complexes. [18] Our continuing efforts will contribute to organometallic chemistry of Co macrocycles, where notable recent results include photocatalytic C-and N-alkylation of indoles [19] and ring-opening copolymerization of CO 2 and propylene oxide. [20] Experimental Section Materials: Literature procedures were followed in the preparations of [Co(TIM)Cl 2 ]PF 6 , [21] 1-ethynyl-4-tertbutylphenyl (HC 2 C 6 H 4 -4-t Bu), [22] 1-ethynyl-4-nitrophenyl (HC 2 C 6 H 4 -4-NO 2 ), [23] and 4-ethynyl-N-mesityl-1,8-naphthalimide (HC 2 NAP Mes ).…”

Formation of an Aza-Cobalt-Cyclobutene on CoIII(TIM): Hidden Noninnocence of the TIM Ligand

“…In conclusion, ample structural and spectroscopic data of compounds 1 , 2a , and 3a support the formation of 1-aza-2-cobalt-cyclobutene, which is attributed to an unprecedented noninnocent behavior of the TIM ligand. Recent years have witnessed exciting new developments in using simple Co macrocyclic complexes to photocatalyze C–C bond formation reactions. , The formation of an aza-cobalt-cyclobutene based on electron-rich terminal alkynes reveals a different facet of Co macrocyclic chemistry, and the incorporation of photoactivity is being investigated.…”

“…Recent years have witnessed exciting new developments in using simple Co macrocyclic complexes to photocatalyze C−C bond formation reactions. 19,20 The formation of an aza-cobalt-cyclobutene based on electron-rich terminal alkynes reveals a different facet of Co macrocyclic chemistry, and the incorporation of photoactivity is being investigated.…”