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.
Nickel-catalyzed cross-coupling reactions of aryl esters, carbamates, carbonates, ethers and arenols are reviewed. Carbon–oxygen bonds in these phenol derivatives cannot be activated by palladium, a ...typical cross-coupling catalyst, but a low valent nickel species in conjunction with a strong σ-donor ligand is uniquely effective for achieving this. The review is organized primarily by substrate class and secondarily by coupling partners, encompassing organometallics, heteroatom nucleophiles, C–H bonds and many others. Although the reactions in this category are covered thoroughly, each reaction is described only briefly, so that it is possible to quickly overview the spectrum of nickel-catalyzed cross-coupling reactions of inert phenol derivatives. The robustness of inert phenol derivatives under typically used catalytic conditions as well as their utility as a directing group allow unique synthetic applications of these new C–O cross-coupling reactions, which is also included in cases where appropriate. Mechanistic aspects of C–O bond activation by nickel are also summarized, highlighting their diversity compared with the C–X bond activation involved in conventional cross-coupling processes.
The first catalytic alkynylation of unactivated C(sp3)–H bonds has been accomplished. The method allows for the straightforward introduction of an ethynyl group into aliphatic acid derivatives under ...palladium catalysis. This new reaction can be applied to the rapid elaboration of complex aliphatic acids, for example, via azide/alkyne cycloaddition.
We report the phosphine-catalyzed intermolecular carbofluorination of alkynes using acyl fluorides as fluorinating reagents. This reaction promises to be a useful method for the synthesis of highly ...substituted monofluoroalkene derivatives since acyl fluorides can be easily prepared from the corresponding carboxylic acid derivatives and the reaction proceeds under ambient conditions without the need for a transition-metal catalyst. Experimental and computational studies indicate that a five-coordinate fluorophosphorane is involved as the key intermediate in the fluorination step.
The first nickel-catalyzed method for the borylation of carbon-hydrogen bonds in arenes and indoles is described. The use of an N-heterocyclic carbene ligand is essential for an efficient reaction, ...with an N-cyclohexyl-substituted derivative being optimal. This method is readily applied to the gram scale synthesis of 2-borylindole.
The nickel-catalyzed reaction of N-aryl amides with hydroborane or diboron reagents resulted in the formation of the corresponding reduction or borylation products, respectively. Mechanistic studies ...revealed that these reactions proceeded via the activation of the C(aryl)–N bonds of simple, electronically neutral substrates and did not require the presence of an ortho directing group.
The rhodium-catalyzed reaction of aryl 2-pyridyl ethers with a diboron reagent results in the formation of arylboronic acid derivatives via activation of the C(aryl)–O bonds. The straightforward ...synthesis of 1,2-disubstituted arenes was enabled through catalytic ortho C–H bond functionalization directed by the 2-pyridyloxy group followed by substitution of this group with a boryl group. Several control experiments revealed that the presence of a sp2 nitrogen atom at the 2-position of the substrate and the use of a boron-based reagent were crucial for the activation of the relatively inert C(aryl)–O bond of aryl 2-pyridyl ethers.
Despite significant progress in the area of C–H bond functionalization of arenes, no general method has been reported for the functionalization of C–H bonds at the sterically encumbered positions of ...simple arenes, such as mesitylene. Herein, we report the development of the first platinum-based catalyst for C–H borylation of arenes and heteroarenes. Notably, this method exhibited high tolerance toward steric hindrance and provided rapid access to a series of 2,6-disubstituted phenylboronic esters, valuable building blocks for further elaborations.
We report herein on the phosphine-catalyzed hydrovinylation reaction by three-component coupling of acyl fluorides, silyl enol ethers, and alkynoates. The key to the success of the reaction is the ...formal transmetalation between pentacoordinate P(V) species (i.e., fluorophosphorane) and a silyl enol ether, which allows for C–C bond formation between the polarity-mismatched sites. The bond formation that cannot be attained even by transition metal catalysis is accomplished by a P(III)/P(V) manifold.
(Phosp)hole in one: A palladium‐catalyzed synthesis for directly assembling phosphole skeletons from triarylphosphines through CH and CP bond cleavage was developed. This approach overcomes several ...of the limitations of the so far reported methods. Phospholes bearing a range of functionalities (including Br, F, CO2Me, Ac, and CN) and an array of fused rings (naphthalenes, anthracenes, furans, and pyrroles) can be easily synthesized.
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