Nickel‐Catalyzed Cross‐Coupling of Aryl Grignard Reagents with Aromatic Alkyl Ethers: An Efficient Synthesis of Unsymmetrical Biaryls

Abstract

Transition-metal-catalyzed cross-coupling reactions play a major role in the formation of C À C bonds. As a result, the cross-coupling of aryl halides (and pseudohalides) with organometallic reagents have become a steadfast method in organic synthesis.[1] This methodology has been used to prepare biaryl compounds, which are prevalent in both natural products and drug compounds.[2] In the more challenging cross-coupling reactions unreactive substrates, such as aryl nitriles, [3] aryl fluorides, [4] and aryl carbamates [5] are coupled with an organometallic reagent and generally require nickel catalysis. Wenkert et al. reported the [NiCl 2 (PPh 3 ) 2 ]-mediated cross-coupling of anisoles with aromatic Grignard reagents.[6] The scope of this process is rather limited, and the only substrates that provide the desired biaryl products in synthetically useful yields are the more reactive 1-and 2-methoxynaphthalene derivatives. In this communication, we report a general, high-yielding nickel-catalyzed cross-coupling of nonactivated aromatic ethers with aryl Grignard reagents.Our initial attempts in cross-coupling an anisole derivative with p-TolMgBr utilized a nickel catalyst prepared in situ from [Ni(acac) 2 ] (acac = acetylacetonyl) and various phosphane ligands in THF. Unfortunately, the reaction did not proceed to completion under any of the conditions tested (Table 1). From these studies, it was found that PCy 3 (Cy = cyclohexyl), an electron-rich ligand, was the best phosphane ligand with [Ni(acac)

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

“…20 The mild reaction conditions achieved allowed for the utilization of Knochel-type Grignards and, more importantly, in the presence of functional groups, a notable finding that is in sharp contrast with classical Kumada-Tamao-Corriu reactions of alkyl ethers. 9,11,12,13,18 Remarkably, it was found that cyclic vinyl ethers reacted with an exquisite stereoselectivity control, thus providing access to the rather elusive Z-homoallylic alcohols. Since other related coupling approaches invariably deliver Econfigured isomers, 21 the ability to obtain selectively Zconfigured homoallylic alcohols shows the complementarity of this method.…”

“…While the methods reported by Wenkert 9 and Dankwardt 11 established the use of aryl methyl ethers as coupling partners in Kumada-Tamao-Corriu reactions, these protocols were essentially limited to the cleavage of C(sp 2 )-O(alkyl) bonds. 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).…”

Nickel(II) complexes with bifunctional phosphine–imidazolium ligands and their catalytic activity in the Kumada–Corriu coupling reaction

“…Since the discovery of the metal-catalysed reaction by Kumada and Corriu in the early 1970s [45,46], many ligands have been reported, especially (chelating) diphosphines [47][48][49][50][51][52][53][54][55][56][57], but very few examples of metal-imidazolium salt systems have been reported. Moreover, catalytic systems involving the reaction of unactivated aryl chlorides with aryl Grignard reagents have been described only recently [58,59].…”

Ethereal C–O Bond Cleavage Mediated by Ni(0)-Ate Complex: A DFT Study

“…As early as in 1979, Wenkert et al 9,10) reported the first Ni-catalyzed Kumada-Tamao type (Mg) [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] reaction, in which aryl methyl ether (ArOMe) acted as the electrophilic partner, and this is now recognized as the first example of Ni-catalyzed activation of an inert C-O bond. However, this breakthrough was overlooked for decades, until quite recently.…”