Zhanxiang Liu

Transition metal-catalyzed C–H bond functionalizations by the use of diverse directing groups

Transition metal-catalyzed direct functionalization of C–H bonds is one of the key emerging strategies that is currently attracting tremendous attention with the aim to provide alternative environmentally friendly and efficient ways for the construction of C–C and C–hetero bonds. In particular, the strategy involving regioselective C–H activation assisted by various functional groups shows high potential, and significant achievements have been made in both the development of novel reactions and the mechanistic study. In this review, we attempt to give an overview of the development of utilizing the functionalities as directing groups. The discussion is directed towards the use of different functional groups as directing groups for the construction of C–C and C–hetero bonds via C–H activation using various transition metal catalysts. The synthetic applications and mechanistic features of these transformations will be discussed, and the review is organized on the basis of the type of directing groups and the type of bond being formed or the catalyst.

Cobalt-Catalyzed Cyclization of Aliphatic Amides and Terminal Alkynes with Silver-Cocatalyst

A new method of cobalt-catalyzed synthesis of pyrrolidinones from aliphatic amides and terminal alkynes was discovered through a C-H bond functionalization process on unactivated sp(3) carbons with the silver cocatalyst using a bidentate auxiliary. For the first time, a broad range of easily accessible alkynes are exploited as the reaction partner in C(sp(3))-H bond activation to give the important 5-ethylidene-pyrrolidin-2-ones in a site-selective fashion. The reaction tolerates a wide variety of functional groups including -F, -Cl, -Br, -CF3, ether, cyclopropane, and thiophene. Both pyridine ligand and aromatic solvent play the important role for the promotion of reactivity. This cobalt-catalyzed cyclization reaction can be successfully extended to a variety of aromatic amides to afford a variety of isoindolinones. Attractive features of this catalytic system include its low cost, easy operation, and convenient access to a wide range of pyrrolidinones and isoindolinones.

Copper-Mediated Synthesis of 1,2,3-Triazoles from N-Tosylhydrazones and Anilines†

Significance: Reported is a remarkable synthesis of 1,4-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles. The reaction of readily available N-tosylhydrazones with anilines is mediated by copper(II) and pivaloic acid. The reaction involves cyclization through C–N and N–N bond formation. This method enables an azide-free access to 1,2,3-triazoles with high efficiency under mild conditions. It exhibits a broad scope tolerating anilines with either electron-withdrawing or -donating groups and a variety of N-tosylhydrazones. More significantly, the two-step synthesis starting from aryl ketones to the desired triazoles can also be executed in a one-pot fashion without compromising the yield. An exclusive high regioselectivity – 1,4-disubstituted or 1,4,5-trisubstituted products – constitutes another advantage of this method. Comment: The most common route to build 1,2,3-triazoles is through Huisgen-type [3+2] cycloadditions. Although numerous methods for the improvement of the Huisgen reaction were reported recently, it is inevitable that an azide (which may sometimes not be readily available) will be involved. To the best of our knowledge, this paper is the first report to synthesize 1,2,3-triazoles without using toxic and potential explosive azide species. A possible tosylhydrazone intermediate (see structure above) of the reaction was proposed and synthesized. Its subsequent treatment with a catalytic amount of copper resulted in the formation of the expected produc. Examples of utilizing heterocyclic amines (e.g., 3-aminopyridine) as substrates in this reaction may be anticipated. Ar1 O

Nickel-Catalyzed Direct Thioetherification of β-C(sp3)–H Bonds of Aliphatic Amides

The nickel-catalyzed β-thioetherification of unactivated C(sp(3))-H bond of propionamides is established with the assistance of 8-aminoquinoline auxiliary, leading to the β-thio carboxylic acid derivatives. A broad range of functional groups is compatible with this thioetherfication reaction. The process represents the first successful example of metal-catalyzed C-S bond formation from unactivated C(sp(3))-H bonds.

Nickel-catalyzed direct amination of arenes with alkylamines.

The efficient nickel-catalyzed direct amination of arenes with simple alkylamines has been achieved with the assistance of a bidentate directing group through sp(2) C-H bond functionalization. Preliminary mechanistic investigations indicate that the reaction probably proceeds through a Ni(I)/Ni(III) catalytic pathway.

Efficient Synthesis of 1,2,3‐Triazoles by Copper‐Mediated CN and NN Bond Formation Starting From N‐Tosylhydrazones and Amines

An effective copper-mediated synthesis of 1,5-dialkyl-4-aryl-1,2,3-triazoles and 1,4-dialkyl-5-aryl-1,2,3-triazoles has been achieved by the use of different N-tosylhydrazones and alkyl amines. The scope of the substrates could be extended from anilines to aliphatic amines when 30 mol % amino acid is added into the reaction mixture. This methodology exhibits many notable features, such as broad substrates scope, high efficiency, and good regioselectivity. Preliminary mechanistic studies indicated that the reaction probably proceeded through a 1-tosyl-2-vinyldiazene intermediate and subsequent aza-Michael addition and N-N bond formation process.

Metal‐Free CN‐ and NN‐Bond Formation: Synthesis of 1,2,3‐Triazoles from Ketones, N‐Tosylhydrazines, and Amines in One Pot

A novel synthetic approach toward 1,4-disubstituted 1,2,3-triazoles by C-N- and N-N-bond formation has been established under transition-metal-free conditions. Complete control of the regioselectivity was successfully achieved. Commercially available anilines, ketones, and N-tosylhydrazine were treated with molecular iodine in one pot to allow the regioselective generation of 1,4-disubstituted 1,2,3-triazoles in high yields without the use of azides.

Synthesis of Sulfur-Bridged Polycycles via Pd-Catalyzed Dehydrogenative Cyclization

A general approach to sulfur-bridged polycycles by palladium-catalyzed double C(sp(2))-H bond oxidative cyclization is presented. This protocol afforded diverse sulfur-bridged five-, six-, and seven-membered polycycles in moderate to good yields with a tolerance for a wide variety of functional groups. A sulfide-bridged six-membered pyrene-thienoacene compound was synthesized readily using this method, and excellent performance for photoluminescence quantum yield was observed.

Cobalt(III)-catalyzed cross-coupling of enamides with allyl acetates/maleimides

Cp*Co(III)-catalyzed direct allylation of enamides has been accomplished with the exclusive formation of allylated Z-enamides with high efficiency. In addition, the employment of maleimides as the reaction partner under the same catalytic conditions provides a series of succinimide-substituted Z-enamides.

Copper-Mediated Aryloxylation and Vinyloxylation of β-C(sp3)–H Bond of Propionamides with Organosilanes

A novel copper-mediated method for the aryloxylation and vinyloxylation of β-C(sp(3))-H bonds of propioamides with organosilanes is described. The reaction proceeds with the assistance of an 8-aminoquinolyl auxiliary in a tandem way by the first oxidation of β-C(sp(3))-H bonds and subsequent arylation/vinylation to give the aryloxylation/vinyloxylation products. This unusual aryloxy/vinyloxy forming reaction offers a new avenue for the functionalization of unactivated sp(3) C-H bonds in organic synthesis.