Ligand-Controlled Nickel-Catalyzed Reductive Relay Cross-Coupling of Alkyl Bromides and Aryl Bromides

Abstract

1,1-Diarylalkanes are important structural frameworks which are widespread in biologically active molecules. Herein, we report a reductive relay cross-coupling of alkyl bromides with aryl bromides by nickel catalysis with a simple nitrogen-containing ligand. This method selectively affords 1,1diarylalkane derivatives with good to excellent yields and regioselectivity.

NiH‐Catalyzed Reductive Relay Hydroalkylation: A Strategy for the Remote C(sp3)−H Alkylation of Alkenes

“…Moreover, a series of heterocycles that are frequently found in medicinally active compounds, including furan ( 2 q ), thiophene ( 2 r ), pyrrole ( 2 s ), indole ( 2 t ), pyridine ( 2 u ), pyrazole ( 2 v ), and benzothiazole ( 2 w ) rings, were also competent coupling partners. Of particular note, secondary alkyl iodides, a class of chain‐walking partners in nickel chemistry,,, were also compatible ( 2 x , 2 y , 2 z ) . Remarkably, migration along the hydrocarbon chain of the secondary alkyl iodide was not observed.…”

Nickel‐Catalyzed Regioselective Hydroalkylation and Hydroarylation of Alkenyl Boronic Esters

“…Thescope of alkyl halides was first probed using 1a as arepresentative alkene partner.Awide range of primary alkyl iodides and bromides were suitable alkylating agents,g iving the hydroalkylation products in good yields (3aa-3an). [14] An acyclics econdary alkyl iodide with ap endant alkene moiety was also av iable reaction partner,e nabling chemo-and regioselective hydroalkylation (3az). Thef ormation of as econdary/secondary C(sp 3 )ÀC(sp 3 )b ond in hydroalkylation is challenging due to steric congestion in the product as well as the general difficulty in cross-coupling of secondary alkyl halides.…”

“…This result was surprising because NiÀHs pecies have been widely reported to catalyze the isomerization of secondary alkyl halides. [14] An acyclics econdary alkyl iodide with ap endant alkene moiety was also av iable reaction partner,e nabling chemo-and regioselective hydroalkylation (3az).…”

Nickel‐Catalyzed 1,1‐Alkylboration of Electronically Unbiased Terminal Alkenes

“…In copper-catalyzed alkylboration reactions,b oth the transient alkyl-Cu intermediate generated from alkene migratory insertion into aC u À Bb ond and the following bond formation mainly benefit from the difficult b-H elimination of the d 10 metal. [13] As part of our ac ontinuing interest in nickel catalysis, [14] particularly after the success of nickel-catalyzed migratory arylboration of alkenes, [15] we speculated that if the copper catalyst was replaced by nickel, rapid b-H elimination and migratory insertion [16] would lead to the formation of as table R-CH(Bpin)Ni II species.T he subsequent C(sp 3 )ÀC(sp 3 )b ond formation, with an alkyl electrophile,w ould deliver the 1,1-alkylboration product. It should be noted that, to the best of our knowledge, only asingle example of nickel-catalyzed 1,1-difunctionalization of alkenes has been demonstrated to date (by the Fu group).…”

“…Anciliary ligands were thought to be the crucial factor for this 1,1-difunctionalization, therefore ligand screens were conducted under similar reaction conditions to our prior arylboration reaction. [14] The ligand effects are illustrated in Table 1. It was surprising that many ligands commonly employed in nickel catalysis,including bipyridine (L1 and L3), 1,10-phenanthroline (L2 and L4), PyrBox (L5), tripyridine (L6)a nd pyrimine (L7)f ailed to gave rise to the desired product 4a in more than at race amount.…”