A highly efficient protocol for the synthesis of pyrrolidones by the copper‐catalyzed alkynylation/annulation of aliphatic amides with alkynyl carboxylic acids is discussed in this paper. A broad range of easily accessible alkynyl carboxylic acids were introduced at the β‐methyl group of aliphatic amides with the assistance of an 8‐aminoquinolyl auxiliary group via decarboxylation to achieve the subsequent cyclic C N bond formation within one hour. High selectivity of β‐methyl groups over methylene groups was observed, and the extension of this catalytic system to the activation of methylene C H bonds failed. The substrates with two different groups at the α‐position of the aliphatic amides lead to the formation of diastereoisomers which is determined by 1H NMR spectroscopy. The initially produced products with Z‐configurations can be easily transformed to the corresponding products with E‐configurations by the treatment with dilute p‐toluenesulfonic acid after the reaction. This catalytic tandem decarboxylative cyclization provides a new opportunity for the direct functionalization of sp3 C H bonds.
The palladium‐catalyzed ketone‐directed dual sp2 C H activation and sp3 C H functionalization has been applied for fullerene functionalization for the first time. The sec‐alkyl aryl ketones have been exploited to react with [60]fullerene (C60) to provide the novel and scarce C60‐fused tetralones. The combined use of a highly active cationic palladium(II) catalyst and trifluoromethanesulfonic acid is crucial for the improvement of the reaction yield. A plausible reaction mechanism leading to the observed products has been proposed, and the electrochemistry of the fullerene products has also been investigated.
A green atom‐economical method for the synthesis of highly functionalized 1‐amino and 1‐carbon substituted isoquinolines from the reaction of N′‐hydroxybenzimidamides and aryl ketoximes, respectively, with alkynes via pentamethylcyclopentadienylcobalt(III)‐catalyzed C H/N O bond activation is described. The external oxidant‐free annulation reaction uses the =NOH moiety in N′‐hydroxybenzimidamides or N‐aromatic ketone oximes as the directing group and internal oxidant. This first row transition metal‐catalyzed annulation serves as an efficient alternative for the synthesis of isoquinolines, as water is the only by‐product and expensive noble metals such as rhodium(III), iridium(III), palladium(II), and ruthenium(II) are not required. The reaction proceeds via C H activation, alkyne insertion, reductive elimination, and N O activation.
Copper salts, which are abundant, relatively inexpensive and possess low toxicity, have long been used as versatile catalysts for various reactions in organic synthesis. Recently, the development of Cu‐catalyzed or ‐mediated C H functionalization reactions has gained significant attention. Since the pioneering work of Daugulis on the introduction of 8‐aminoquinoline and picolinic acid auxiliaries as removable directing groups in transition metal‐catalyzed C H bond activations, the combination of copper salts with these bidentate directing groups has emerged as an innovative strategy for the construction of carbon‐carbon or carbon‐heteroatom bonds through C H bond cleavage. In addition to the 8‐aminoquinoline and picolinamide systems, several other bidentate directing groups including the 2‐aminophenyloxazoline group by Yu and Dai and the PIP system by Shi, have been developed as well. This review intends to cover most of the recent advances on copper‐catalyzed or ‐mediated direct sp2 and sp3 C H bond functionalizations assisted by these bidentate directing groups. The major achievements in this area are discussed and catalogued by the type of bonds formed (C C, C O, C N, C S, C P etc.). Special attention is paid to the reaction mechanisms. Selected examples of substrates are listed as well. In addition, a personal outlook is given at the end.
The direct functionalization of inert sp3 C H bonds is limited to a few bond types. Although the activation of sp3 C H bonds can be accomplished under mild conditions using palladium catalysts, the subsequent functionalization is not trivial due to the high energy required to convert palladium(II) to palladium(IV). We have systematically studied the palladium oxidation using computation‐guided experiments for reactions involving strong chelation control. We find that a mild external ligand could significantly accelerate the oxidation of palladium(II) to palladium(IV) for strong bidentate directing groups. The acceleration is believed to be a result of ligand stabilization of both the palladium(II) and palladium(IV) intermediates.
We report here that a cobalt catalyst generated from a cobalt(II) salt and a ligand using magnesium metal is capable of promoting hydroarylation reactions through chelation‐assisted C−H activation. With the appropriate choice of the ligand and other reaction conditions, ketimine‐ or aldimine‐directed branched selective hydroarylations of styrenes and ketimine‐directed hydroarylations of vinylsilane have been achieved. The reported catalytic systems may serve as more convenient alternatives to previously developed catalytic systems employing Grignard reagents as reducing agents.
With molybdenum hexacarbonyl as the carbon monoxide source, a general palladium‐catalyzed carbonylative transformation of the C−H bond on aromatic rings to produce esters has been developed. Good yields of the corresponding products have been obtained with wide functional group tolerance and excellent regioselectivity. A variety of aliphatic alcohols are suitable reactants here.
The ruthenium(II)‐ or rhodium(III)‐catalyzed pyrimidinyl‐directed Grignard‐type C−H additions of N‐heterocycles with activated aldehydes and ketones are described. A cationic ruthenium catalyst and sodium acetate additive in dichloroethane as solvent were found to be optimal catalytic system for the construction of C‐7 alkylated indolines. In sharp contrast, a cationic rhodium complex allows the generation of C‐2 alkylated indoles and pyrroles as well as C‐1 alkylated carbazoles. The site‐selective C−H functionalization of these heterocyclic scaffolds could be an important asset towards the development of novel bioactive compounds.
