In recent years, transition‐metal‐catalyzed C−H activation has become a key strategy in the field of organic synthesis. Rhodium complexes are widely used as catalysts in a variety of C−H ...functionalization reactions because of their high reactivity and selectivity. The availability of a number of rhodium complexes in various oxidation states enables diverse reaction patterns to be obtained. Regioselectivity, an important issue in C−H activation chemistry, can be accomplished by using a directing group to assist the reaction. However, to obtain the target functionalized compounds, it is also necessary to use a directing group that can be easily removed. A wide range of directed C−H functionalization reactions catalyzed by rhodium complexes have been reported to date. In this Review, we discuss Rh‐catalyzed C−H functionalization reactions that are aided by the use of a removable directing group such as phenol, amine, aldehyde, ketones, ester, acid, sulfonic acid, and N‐heteroaromatic derivatives.
Directors cut: The beneficial use of removable directing groups in the Rh‐catalzyed C−H functionalization of organic compounds is discussed in this Review. Various key strategies that are currently used in selective organic synthesis are highlighted.
CH bonds are ubiquitous in organic compounds. It would, therefore, appear that direct functionalization of substrates by activation of CH bonds would eliminate the multiple steps and limitations ...associated with the preparation of functionalized starting materials. Regioselectivity is an important issue because organic molecules can contain a wide variety of CH bonds. The use of a directing group can largely overcome the issue of regiocontrol by allowing the catalyst to come into proximity with the targeted CH bonds. A wide variety of functional groups have been evaluated for use as directing groups in the transformation of CH bonds. In 2005, Daugulis reported the arylation of unactivated C(sp3)H bonds by using 8‐aminoquinoline and picolinamide as bidentate directing groups, with Pd(OAc)2 as the catalyst. Encouraged by these promising results, a number of transformations of CH bonds have since been developed by using systems based on bidentate directing groups. In this Review, recent advances in this area are discussed.
Caught in the act: The regiochemical functionalization of CH bonds is a reliable strategy in synthetic chemistry. The regiocontrol can be achieved by using a directing group in the substrate which brings the catalyst into proximity with the target CH bond. Bidentate directing groups in particular have proven to be extremely effective.
During the past decades, synthetic organic chemistry discovered that directing group assisted C–H activation is a key tool for the expedient and siteselective construction of C–C bonds. Among the ...various directing group strategies, bidentate directing groups are now recognized as one of the most efficient devices for the selective functionalization of certain positions due to fact that its metal center permits fine, tunable, and reversible coordination. The family of bidentate directing groups permit various types of assistance to be achieved, such as N,N-dentate, N,O-dentate, and N,S-dentate auxiliaries, which are categorized based on the coordination site. In this review, we broadly discuss various C–H bond functionalization reactions for the formation of C–C bonds with the aid of bidentate directing groups.
The Ni-catalyzed, direct arylation of C(sp3)–H (methyl and methylene) bonds in aliphatic amides containing an 8-aminoquinoline moiety as a bidentate directing group with aryl halides is described. ...Deuterium-labeling experiments indicate that the C–H bond cleavage step is fast and reversible. Various nickel complexes including both Ni(II) and Ni(0) show a high catalytic activity. The results of a series of mechanistic experiments indicate that the catalytic reaction does not proceed through a Ni(0)/Ni(II) catalytic cycle, but probably through a Ni(II)/Ni(IV) catalytic cycle.
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.
•An overview of the strategic evolution in C-H activation chemistry is provided.•The chronological evolution of directed C-H functionalization is discussed.•The history of built-in and removable ...directing groups is outlined.•Distal C-H functionalization with a working hypothesis is presented.
In the field of C–H bond functionalization chemistry, directed C–H bond activation strategies are highly appreciated due to the high efficiency and selectivity of such reactions towards a certain type of C–H bond. Considering extraordinarily rapid progress in directed C–H bond functionalization reactions, we summarize the strategic evolution of directed C–H bond activation chemistry in this review. We feel that this review would be of particular interest to scientists who are interested in progress made in the area of directed C–H bond functionalization, which could stimulate new areas of research regarding this significant topic.
Considerable advances have been made in the area of C−H functionalization in the last few decades. A number of approaches including both directed and nondirected strategies have been developed thus ...far. Among the various C−H functionalizations, C−H borylation is of special interest due to the wide applications of organoboron compounds. In this regard, various transition‐metal‐catalyzed regioselective strategies have been developed. However, the major concern regarding metal‐catalyzed C−H borylation procedures is the requirement of a precious metal as well as the contamination by metal precursors in the desired products, which limit the application of this process in large‐scale synthesis. Therefore, recent trends have involved the use of transition‐metal‐free systems. We summarize recent developments in transition‐metal‐free regioselective C−H borylation. We believe that this Review will help to increase interest in this field and stimulate further progress.
Recent developments in strategies for transition‐metal‐free regioselective C−H borylation are summarized in this Review. Strategies developed to control the regioselectivity of the electrophilic borylation, such as approaches controlled by electronic effects, auxiliaries, and steric factors, are also discussed. EDG=electron donating group, DG=directing group, TM=transition metal.
Organoboron reagents are important synthetic intermediates and have wide applications in synthetic organic chemistry. The selective borylation strategies that are currently in use largely rely on the ...use of transition-metal catalysts. Hence, identifying much milder conditions for transition-metal-free borylation would be highly desirable. We herein present a unified strategy for the selective C–H borylation of electron-deficient benzaldehyde derivatives using a simple metal-free approach, utilizing an imine transient directing group. The strategy covers a wide spectrum of reactions and (i) even highly sterically hindered C–H bonds can be borylated smoothly, (ii) despite the presence of other potential directing groups, the reaction selectively occurs at the o-C–H bond of the benzaldehyde moiety, and (iii) natural products appended to benzaldehyde derivatives can also give the appropriate borylated products. Moreover, the efficacy of the protocol was confirmed by the fact that the reaction proceeds even in the presence of a series of external impurities.
The palladium‐catalyzed 3+2 annulation of aromatic amides with maleimides via the activation of ortho benzylic C−H and meta C−H bonds is reported. Carboxamide and anilide type substrates that contain ...a 2‐methylthiophenyl group both participate in this 3+2 annulation, indicating that the presence of a 2‐methylthiophenyl directing group is a key for the success of the reaction. The first C−H bond activation at the benzylic C−H bond is followed by a second C−H bond activation at the meta C−H bond to give five‐membered cyclic products. The cleavage of these C−H bonds is irreversible.
The palladium‐catalyzed site‐selective 3+2 annulation of amides with maleimides via the activation of ortho benzylic C−H and meta C−H bonds is reported. The presence of a 2‐methylthiophenyl directing group is a key for the success of the reaction.
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