Naoto Chatani

Catalytic Functionalization of C(sp2)H and C(sp3)H Bonds by Using Bidentate Directing Groups

C-H bonds are ubiquitous in organic compounds. It would, therefore, appear that direct functionalization of substrates by activation of C-H 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 C-H 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 C-H bonds. A wide variety of functional groups have been evaluated for use as directing groups in the transformation of C-H bonds. In 2005, Daugulis reported the arylation of unactivated C(sp(3))-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 C-H bonds have since been developed by using systems based on bidentate directing groups. In this Review, recent advances in this area are discussed.

Nickel‐Catalyzed Cross‐Coupling of Aryl Methyl Ethers with Aryl Boronic Esters

Palladiumand nickel-catalyzed cross-coupling reactions have been recognized as an indispensable tool for current organic synthesis. Among these reactions, Suzuki–Miyaura coupling is, arguably, of the greatest practical importance of these methods because of the attractive features of organoboronic acids: widespread availability, stability to air and moisture, and low toxicity. Recently, tremendous progress has been made in the development of more elaborate catalyst systems that allow the couplings to be conducted at room temperature, to use unreactive chlorides, and to use alkyl electrophiles. Despite these significant advances, the electrophilic coupling partner for use in Suzuki–Miyaura coupling remains limited, for the most part, to organic halides and sulfonates; although the use of less available electrophiles, including diazonium salts, ammonium salts, aryltriazene/BF3, [7c] azoles, and phosphonium salts has been reported. Aryl methyl ethers, which are as readily available as aryl halides, have never been used in the Suzuki–Miyaura coupling reaction, except for the ruthenium-catalyzed system, which requires a ligating group at the ortho position for the reaction to proceed. Herein, we describe a method for the nickel-catalyzed cross-coupling of aryl methyl ethers with boronic esters [Eq. (1)]. The advantages of using aryl alkyl ethers in the metalcatalyzed cross-coupling reaction have been documented by Wenkert and Dankwardt in the nickel-catalyzed reaction with Grignard reagents (i.e., Kumada–Tamao–Corriutype coupling). Although functional-group compatibility and availability of the starting Grignard reagents for these initial methods are rather limited, these pioneering studies offer a starting point for the development of cross-coupling reactions between aryl methyl ethers and organoboron reagents. Thus, we investigated the reaction of 2-methoxynaphthalene (1a) with organoboron compounds in the presence of a catalytic amount of [Ni(cod)2] (cod= cycloocta-1,5-diene) and PCy3 (Table 1). Whereas attempts with boronic acid (Table 1, entry 1) and borates (Table 1, entries 2 and 3) were unsuccessful, cross-coupling with boronic ester 2a furnished the product in modest yield (Table 1, entry 4). Although the

Nickel-Catalyzed Direct Alkylation of C–H Bonds in Benzamides and Acrylamides with Functionalized Alkyl Halides via Bidentate-Chelation Assistance

The alkylation of the ortho C-H bonds in benzamides and acrylamides containing an 8-aminoquinoline moiety as a bidentate directing group with unactivated alkyl halides using nickel complexes as catalysts is described. The reaction shows high functional group compatibility. In reactions of meta-substituted aromatic amides, the reaction proceeds in a highly selective manner at the less hindered C-H bond.

Nickel-catalyzed direct arylation of C(sp3)-H bonds in aliphatic amides via bidentate-chelation assistance.

The Ni-catalyzed, direct arylation of C(sp(3))-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.

Palladium-Catalyzed Direct Ethynylation of C(sp3)–H Bonds in Aliphatic Carboxylic Acid Derivatives

The first catalytic alkynylation of unactivated C(sp(3))-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.

Nickel-catalyzed chelation-assisted transformations involving ortho C-H bond activation: regioselective oxidative cycloaddition of aromatic amides to alkynes.

Although the pioneering example of ortho metalation involving cleavage of C-H bonds was achieved using a nickel complex (Kleiman, J. P.; Dubeck, M. J. Am. Chem. Soc. 1963, 85, 1544), no examples of catalysis using nickel complexes have been reported. In this work, the Ni-catalyzed transformation of ortho C-H bonds utilizing chelation assistance, such as oxidative cycloaddition of aromatic amides with alkynes, has been achieved.

Nickel-catalyzed reaction of arylzinc reagents with N-aromatic heterocycles: a straightforward approach to C-H bond arylation of electron-deficient heteroaromatic compounds.

The reaction of electron-deficient N-heteroaromatic compounds, such as pyridines and quinolines, with arylzinc reagents in the presence of a catalytic amount of a nickel complex affords the arylated products. The reaction is likely to proceed through a formal nucleophilic 1,2-addition, thus exhibiting a reactivity complementary to conventional direct arylation through electrophilic substitution.

Highly regioselective carbonylation of unactivated C(sp3)-H bonds by ruthenium carbonyl.

The regioselective carbonylation of unactivated C(sp(3))-H bonds of aliphatic amides was achieved using Ru(3)(CO)(12) as a catalyst. The presence of a 2-pyridinylmethylamine moiety in the amide is crucial for a successful reaction. The reaction shows a preference for C-H bonds of methyl groups as opposed to methylene C-H bonds and tolerates a variety of functional groups. The stoichiometric reaction of an amide with Ru(3)(CO)(12) gave a dinuclear ruthenium complex in which the 2-pyridinylmethylamino moiety was coordinated to the ruthenium center in an N,N manner.

Ruthenium-catalyzed carbonylation at ortho C-H bonds in aromatic amides leading to phthalimides: C-H bond activation utilizing a bidentate system.

A new type of carbonylation of the ortho C-H bonds in aromatic amides 1, in which the pyridin-2-ylmethylamino moiety functions as a bidentate directing group, can be achieved. The presence of ethylene as a hydrogen acceptor and also of H(2)O, probably for the generation of an active catalytic species, is required. A wide variety of functional groups, including methoxy, amino, ester, ketone, cyano, chloro, and even bromo substituents, can be substituted for aromatic amides. The complex 9 was isolated by the stoichiometric reaction of 1b and Ru(3)(CO)(12), in which 1b binds to one Ru atom in the expected N,N fashion and the carbonyl oxygen binds to the other Ru atom as an O donor.

Modular Synthesis of Phenanthridine Derivatives by Oxidative Cyclization of 2-Isocyanobiphenyls with Organoboron Reagents†

Where HAS you been? A manganese-mediated annulation of 2-isocyanobiaryls with organoboronic acids is developed for the synthesis of a broad range of phenanthridine derivatives. Mechanistic studies indicate that the reaction proceeds by the intramolecular homolytic aromatic substitution (HAS) of an imidoyl radical intermediate.