Cross-Couplings Using Aryl Ethers via C–O Bond Activation Enabled by Nickel Catalysts

Abstract

Arene synthesis has been revolutionized by the invention of catalytic cross-coupling reactions, wherein aryl halides can be coupled with organometallic and organic nucleophiles. Although the replacement of aryl halides with phenol derivatives would lead to more economical and ecological methods, success has been primarily limited to activated phenol derivatives such as triflates. Aryl ethers arguably represent one of the most ideal substrates in terms of availability, cost, safety, and atom efficiency. However, the robust nature of the C(aryl)-O bonds of aryl ethers renders it extremely difficult to use them in catalytic reactions among the phenol derivatives. In 1979, Wenkert reported a seminal work on the nickel-catalyzed cross-coupling of aryl ethers with Grignard reagents. However, it was not until 2004 that the unique ability of a low-valent nickel species to activate otherwise unreactive C(aryl)-O bonds was appreciated with Dankwardt's identification of the Ni(0)/PCy3 system, which significantly expanded the efficiency of the Wenkert reaction. Application of the nickel catalyst to cross-couplings with other nucleophiles was first accomplished in 2008 by our group using organoboron reagents. Later on, several other nucleophiles, including organozinc reagents, amines, hydrosilane, and hydrogen were shown to be coupled with aryl ethers under nickel catalysis. Despite these advances, progress in this field is relatively slow because of the low reactivity of benzene derivatives (e.g., anisole) compared with polyaromatic substrates (e.g., methoxynaphthalene), particularly when less reactive and synthetically useful nucleophiles are used. The "naphthalene problem" has been overcome by the use of N-heterocyclic carbene (NHC) ligands bearing bulky N-alkyl substituents, which enables a wide range of aryl ethers to be coupled with organoboron nucleophiles. Moreover, the use of N-alkyl-substituted NHC ligands allows the use of alkynylmagnesium reagents, thereby realizing the first Sonogashira-type reaction of anisoles. From a mechanistic perspective, nickel-catalyzed cross-couplings of aryl ethers are at a nascent stage, in particular regarding the mode of activation of C(aryl)-O bonds. Oxidative addition is one plausible pathway, although such a process has not been fully verified experimentally. Nickel-catalyzed reductive cleavage of aryl ethers in the absence of an external reducing agent provides strong support for this oxidative addition process. Several other mechanisms have also been proposed. For example, Martin demonstrated a new possibility of the involvement of a Ni(I) species, which could mediate the cleavage of the C(aryl)-O bond via a redox-neutral pathway. The tolerance of aryl ethers under commonly used synthetic conditions enables alkoxy groups to serve as a platform for late-stage elaboration of complex molecules without any tedious protecting group manipulations. Aryl ethers are therefore not mere economical alternatives to aryl halides but also enable nonclassical synthetic strategies.

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

“…[51][52][53][54] Martin and colleagues reported that direct OA of a E C-O bond to Ni(0) requires high temperature, based on experimental and theoretical findings. 46) Computational studies by Nakamura and colleagues, 55) Liu and colleagues, 56) Martin and colleagues, 46) and us 14) clearly demonstrated that OA of a E C-O bond generally involves a very high activation barrier (Chart 2(1)), even considering the Lewis acidity of Mg (Chart 2 (2)). This could be attributed to the high stability of the E C-O bond and the weak interaction between the E C-O moiety and Ni(0) species.…”

“…Based on this work, together with our previous mechanistic study on etheric Kumada-Tamao reaction, we identify and characterize a novel catalytic cycle for cross-coupling mediated by Ni(0)-ate complex.Key words cross-coupling; ether; nickel catalyst; organolithium; organozinc; density functional theory (DFT) calculation Efficient and selective cleavage and transformation of C-O bonds, particularly by means of cross-coupling methods, has attracted great interest, since compounds containing C-O moieties occur widely in nature and are also extensively utilized in industry.1-8) Among C-O compounds, ethers are particularly attractive, [1][2][3][4][5][6][7][8] as they offer the advantages of 1) high atom economy/conversion efficiency (the use of ethers as simple as MeO as substrates affords fewer by-products compared with tosylate, mesylate, triflate, phosphate, etc. ), 2) environmental compatibility (cleavage of the C-O moiety in ether releases non-halogen-containing waste), and 3) excellent stability, easy accessibility and wide diversity.…”

“…1-8) Among C-O compounds, ethers are particularly attractive, [1][2][3][4][5][6][7][8] as they offer the advantages of 1) high atom economy/conversion efficiency (the use of ethers as simple as MeO as substrates affords fewer by-products compared with tosylate, mesylate, triflate, phosphate, etc. ), 2) environmental compatibility (cleavage of the C-O moiety in ether releases non-halogen-containing waste), and 3) excellent stability, easy accessibility and wide diversity.…”

Complete lignocellulose conversion with integrated catalyst recycling yielding valuable aromatics and fuels

“…Next, we established the direct conversion of 3G to aniline derivatives (Fig. 6c) through homogeneous nickel-catalysed crosscoupling 34,35 using a variety of amines and pseudohalogenide 8 that was obtained from 3G. Gratifyingly, 8 underwent cross-coupling with a number of amines to yield the corresponding aromatic products 9a-9e.…”

Nickel-Catalyzed Cross-Coupling Reactions of Unreactive Phenolic Electrophiles via C–O Bond Activation

“…Catalytic transformations via alkenyl [17][18][19][20][21][22][23][24][25][26][27][28] and benzylic C-O bond [29,30] activation are not covered. In addition, readers are encouraged to consult previous reviews on catalytic C-O bond activation reactions [31][32][33][34][35][36][37][38]. …”