Direct Benzylic Alkylation via Ni-Catalyzed Selective Benzylic sp³ C−O Activation

Abstract

This article demonstrates the first cross coupling of benzyl ether with Grignard reagents via Ni-catalyzed benzylic sp3 C−O activation with high efficiency and excellent chemoselectivity. Benzylic sp3 C−O and aryl sp2 C−O were differentiated, controlled by ligands.

Recent advances in homogeneous nickel catalysis

“…37 Benzylic ethers, esters, carbonates, carbamates, and in some instances, even free alcohols (via the corresponding magnesium alkoxide) can be activated by low-valent nickel. With proper choice of starting material and organometallic reagent, the reaction products can be di- or triarylalkanes, both of which are ubiquitous motifs in drug targets, natural products, and materials applications.…”

Metal-catalyzed activation of ethers via C–O bond cleavage: a new strategy for molecular diversity

“…The Shi group described a Ni-catalyzed methodology that allowed for the coupling of activated benzyl alkyl ethers with MeMgBr via C(sp 3 )-O bond-cleavage (Scheme 11). 22 Interestingly, while NiCl 2 (PCy 3 ) 2 delivered traces of the coupling product, NiCl 2 (dppf) 2 provided the best results in toluene at 80 ºC. Under these reaction conditions, a wide variety of primary or even secondary benzyl alkyl ethers could be utilized with similar efficiency.…”

Nickel‐Catalyzed Cross‐Coupling of Styrenyl Epoxides with Boronic Acids

“…[11] On the basis of recent studies on CÀO bond activation, [12] we first examined [NiCl 2 (PCy 3 ) 2 ] as a catalyst precursor for the coupling of p-tol styrene oxide and PhB(OH) 2 ; gratifyingly, the cross-coupled product was observed, albeit in low yield ( [14] To our knowledge, this reaction represents the first application of this ligand to a nickel-catalyzed process.…”