Cooperative triple catalysis enables regioirregular formal Mizoroki–Heck reactions

Abstract

The Mizoroki–Heck reaction between alkenes and aryl halides represents one of the most important methods for C−C bond formation in synthetic chemistry. Governed by their electronic and steric nature, alkenes are generally arylated with high regioselectivity, which conversely hampers diversity, in particular, if the regioirregular isomer is targeted. Usually, electron-poor alkenes selectively afford the corresponding β-coupled products, and achieving the opposite regioselectivity to obtain their α-arylated congeners is highly challenging. It would be desirable to access the irregular α-regioisomer by simple variation of the reaction conditions, keeping the standard substrates, thereby significantly enlarging the product space. Herein, we describe an intermolecular α-arylation of electron-poor alkenes through cooperative nickel, photoredox and sulfinate catalysis. This triple catalysis system operates under mild conditions and features excellent functional group tolerance. The orchestration of radical, transition metal and ionic bond-forming and -cleaving reactions in a single process is highly challenging, but certainly opens valuable doors in terms of reactivity. Moreover, the intermolecular α-arylation, α-alkenylation and α-alkynylation of styrenes could also be achieved through a one-pot process.

Radical NHC Catalysis

“…Sulfinates are often used as potent SET donors for radical reactions. , In 2020, Studer and co-workers reported three-component coupling of alkenes, benzoyl fluorides, and NaSO 2 CF 3 to access β-trifluoromethylated ketones using cooperative NHC/photoredox catalysis (Scheme ). Upon irradiation, NaSO 2 CF 3 was converted to a trifluoromethyl radical through single-electron oxidation by the Ir-based photoredox catalyst and subsequent SO 2 fragmentation.…”

Nickel-Catalyzed Heck Reaction

“…This owes to the unique behavior of nickel as a transition metal to entwine with other systems. 5 Nickel metal salts, its complexes 6 along with Ni bimetallic systems, 7 alloys, and Ni nanoparticles 8 lead to extensive catalytic applicability. Nickel catalysts along with phosphine-based ligands were also extensively used by researchers for Heck reaction.…”

“…Table 1 presents recent protocols involving diversified forms of nickel (a non-noble metal) complexes as catalyst. 5 discovered a new synergism of three catalytic cycles involving photoredox steps, sulfinate catalysis, and various transition states of Ni. Even different aryl/heteroaryl bromides reacted well with styrenes and electronwithdrawing alkenes to afford the large series of desired products.…”

Nickel-catalyzed divergent Mizoroki–Heck reaction of 1,3-dienes

“…Among them, Mizoroki-Heck reaction has been recognized as an elegant strategy for carboarylations of alkenes [9][10][11][12][13] . However, most of current Mizoroki-Heck reactions focused on the arylation of mono alkenes [14][15][16][17][18][19][20][21][22] or using noble palladium catalysts 23 (Fig. 1a).…”