Nickel‐Catalyzed C(sp²)−C(sp³) Kumada Cross‐Coupling of Aryl Tosylates with Alkyl Grignard Reagents

Abstract

Aryl tosylates are an attractive class of electrophiles for cross-coupling reactions due to ease of synthesis, low price, and the employment of CÀ O electrophiles, however, the reactivity of aryl tosylates is low. Herein, we report the Ni-catalyzed C(sp 2 )À C(sp 3 ) Kumada cross-coupling of aryl tosylates with primary and secondary alkyl Grignard reagents. The method delivers valuable alkyl arenes by cross-coupling with challenging alkyl organometallics possessing β-hydrogens that are prone to β-hydride elimination and homocoupling. The reaction is catalyzed by an air-and moisture stable-Ni(II) precatalyst. A broad range of electronically-varied aryl tosylates, including bis-tosylates, underwent this transformation, and many examples are suitable at mild room temperature conditions. The combination of ArÀ X cross-coupling with the facile ArÀ OH activation/cross-coupling strategy permits for orthogonal cross-coupling with challenging alkyl organometallics. Furthermore, we demonstrate that the method operates with TON reaching 2000, which is one of the highest turnovers observed to date in Ni-catalyzed cross-couplings.

Chemodivergence between Electrophiles in Cross‐Coupling Reactions

“…Kambe's 2003 report suggested that nickel is less selective than Pd in Kumada couplings of chloroalkyl (or bromoalkyl) tosylates [52] . This observation was corroborated by a separate study by Szostak in 2019 [56] . In the presence of a Ni/dppe catalyst, 1‐chloronaphthalene and 1‐naphthyl tosylate react with an alkyl Grignard reagent at essentially identical rates, resulting in about 50 % recovery of each starting material (Scheme 20).…”

“… A nickel/dppe‐catalyst does not discriminate between an aryl tosylate and chloride during a Kumada coupling [56] …”

“…[52] This observation was corroborated by as eparate study by Szostaki n2 019. [56] In the presence of aN i/dppe catalyst, 1-chloronaphthalene and 1-naphthyl tosylate reactw ith an alkyl Grignardr eagent at essentially identical rates, resulting in about 50 %r ecovery of each startingm aterial( Scheme 20).…”

Transition-Metal-Catalyzed Cross-Coupling Reactions of Grignard Reagents

“…Szostak and co-workers reported the Kumada-Tamao-Corriu cross-coupling of aryl tosylates 32 with alkyl Grignard reagents 14Cl in the presence of the stable NiCl 2 (dppe) precatalyst (Scheme 15). 43 Li and coworkers, however, achieved the Ni(acac) 2 -catalyzed crosscoupling of aryl tosylates 32 with aryl Grignard reagents 14Cl promoted by LiCl. 44 They demonstrated that LiCl accelerated the reduction of Ni(II) to Ni(0).…”

Iron-Catalyzed Cross-Coupling Reactions of Alkyl Grignards with Aryl Chlorobenzenesulfonates

“…Furthermore, aryl sulfonate esters play an important role in organic chemistry as synthetic intermediates, which is related to their versatile application as protecting groups and C–O electrophiles in organic reactions. The resistance of the sulfonate groups to various reaction conditions makes them handy protecting groups for phenols [ 30 , 31 ], while the possibility to activate the C–O bond using transition metal catalysis makes them a valuable alternative to aryl halides in cross-coupling reactions [ 32 , 33 , 34 , 35 , 36 ]. It is worth noting that in both variants, the resulting target products do not contain a sulfonate ester moiety, which is deconstructed under basic or transition-metal-catalyzed conditions.…”