Access to N-Heterocyclic Molecules via Ru(II)-Catalyzed Oxidative Alkyne Annulation Reactions

In the last few decades, the transition metal‐catalyzed activation of inert C−H bonds has led to a fundamental change in the field of synthetic chemistry. Most of these C−H activation reactions deal with simple functionalizations or additions. However, recent years have witnessed an increase of the transition metal‐catalyzed activation of C−H bond and annulation reactions. These annulation reactions are appealing to the organic chemist as they afford highly valuable cyclic compounds in a rapid and sustainable manner from readily available compounds. This review article attempts to highlight the recent advances in the ruthenium metal‐catalyzed C−H bond activation and alkyne annulation reactions.magnified image

The catalytic chemistry of nitric oxide

An Ir(III)-catalyzed annulation of aryl amides with 1,6-diynes via ortho- as well as meta-dual C-H bond activation reaction is reported. The scope of the annulation reaction was examined with various substituted aryl amides, as well as 1,6-diynes. In this protocol, 1,6-diynes exhibit diverse reactivity compared with internal alkynes. It is important to note that the three C-C bond formation takes place consecutively via ortho followed by meta-dual C-H bond annulation by using a weak chelating group in one pot. A possible catalytic reaction mechanism was proposed to account for the annulation reaction.

A rhodium-catalyzed sequential oxidative C–H annulation reaction between ketazines and internal alkynes has been developed via C–H and N–N bond activation with air as an external oxidant, which led to an efficient approach toward isoquinolines with high atom efficiency at rt. Utilizing the distinctive reactivity of this catalysis, both N-atoms of the azines could be efficiently incorporated to the desired isoquinolines under very robust and mild reaction conditions.

A rhodium-catalyzed sequential oxidative C-H annulation reaction between ketazines and internal alkynes has been developed via C-H and N-N bond activation with air as an external oxidant, which led to an efficient approach toward isoquinolines with high atom efficiency at rt. Utilizing the distinctive reactivity of this catalysis, both N-atoms of the azines could be efficiently incorporated to the desired isoquinolines under very robust and mild reaction conditions.

The catalyst-dependent intermolecular carbonyl-alkyne metathesis (CAM) reaction of 1H-indene-1,2,3-triones with internal alkynes was realized using Ru and Co catalysts. 2-(2-Oxo-1,2-diphenylethylidene)-1H-indene-1,3(2H)-dione derivatives were obtained using a Ru catalyst, whereas S-alkyl 2-(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)-2-phenylethanethioates were prepared using a Co catalyst. These transformations led to the synthesis of α,β-unsaturated carbonyl compounds with a broad substrate scope, excellent regiocontrol, and gram-scale amenability. This catalytic strategy using a Co or Ru catalyst has rarely been described for other established CAM catalysts.

The cationic ruthenium hydride complex [(PCy(3))(2)(CO)(CH(3)CN)(2)RuH](+)BF(4)(-) was found to be a highly effective catalyst for the C-H bond activation reaction of arylamines and terminal alkynes. The regioselective catalytic synthesis of substituted quinoline and quinoxaline derivatives was achieved from the ortho-C-H bond activation reaction of arylamines and terminal alkynes by using the catalyst Ru(3)(CO)(12)/HBF(4).OEt(2). The normal isotope effect (k(CH)/k(CD) = 2.5) was observed for the reaction of C(6)H(5)NH(2) and C(6)D(5)NH(2) with propyne. A highly negative Hammett value (rho = -4.4) was obtained from the correlation of the relative rates from a series of meta-substituted anilines, m-XC(6)H(4)NH(2), with sigma(p) in the presence of Ru(3)(CO)(12)/HBF(4).OEt(2) (3 mol % Ru, 1:3 molar ratio). The deuterium labeling studies from the reactions of both indoline and acyclic arylamines with DCCPh showed that the alkyne C-H bond activation step is reversible. The crossover experiment from the reaction of 1-(2-amino-1-phenyl)pyrrole with DCCPh and HCCC(6)H(4)-p-OMe led to preferential deuterium incorporation to the phenyl-substituted quinoline product. A mechanism involving rate-determining ortho-C-H bond activation and intramolecular C-N bond formation steps via an unsaturated cationic ruthenium acetylide complex has been proposed.

Platinum group metals as catalysts in enantioselective 1-phenylpropane-1,2-dione hydrogenation

Ru(II)-catalyzed redox-neutral [3+2] annulation reactions of N-ethoxycarbamoyl indoles and internal alkynes via C-H bond activation are reported. This method features a broad internal alkyne scope, including various aryl/alkyl-, alkyl/alkyl-, and diaryl-substituted alkynes, good to excellent regioselectivity, diverse functional group tolerance, and mild reaction conditions. The N-ethoxycarbamoyl directing group, temperature, CsOAc, and ruthenium catalyst proved to be crucial for conversion and high regioselectivity. Additionally, preliminary mechanistic experiments were conducted, and a possible mechanism was proposed.

Phthalazinones and their higher congeners are commonly prevalent structural motifs that occur in natural products, bioactive molecules, and pharmaceuticals. In the past few decades, transition-metal-catalyzed reactions have received an overwhelming response from organic chemists as challenging organics and heterocycles could be built with ease. Currently, the synthesis of phthalazinones largely depends on transition-metal catalysis, especially by palladium-catalyzed carbonylation. Further, the dominance of transition-metal catalysts was realized from the phthalazinones viewpoint, as nitrogen and oxygen atoms endowed upon them act as directing groups to facilitate diverse C-H activation/functionalization/annulation reactions. This highlight describes the various synthetic methods used to access phthalazinones and functionalize them by reacting with various coupling partners via chelation assistance strategy involving C(sp2)-H/N-H bond activation in the presence of transition-metal (Rh, Ru, Pd, and Ir) catalysts. The mechanisms of sulfonylation, halogenation, acylmethylation, alkylation, and annulation reactions are discussed.

Synthesis of ammonium cyanate and urea from NO over Pt, Os, Ru, and CuNi catalysts

Dry reforming of methane over supported Rh and Ru catalysts: Effect of the support (Al2O3, TiO2, ZrO2, YSZ) on the activity and reaction pathway

SummaryTransition metal catalyzed [3 + 2] annulation of imines with double bonds via directed C-H activation offers a direct access to amino cyclic motifs. However, owing to weak coordination and steric hindrance, trifluoromethylated ketimines have been an unaddressed challenge for TM-catalyzed annulations. Here, a rhenium-catalyzed [3 + 2] annulation of trifluoromethylated ketimines with isocyanates via C(sp2)-H activation has been disclosed. This approach provides an efficient platform for rapid access to a privileged library of CF3-containing iminoisoindolinones and polyamides by utilizing challenging CF3-ketimines as the annulation component. The capability of gram scale synthesis, the post-functionalization of the cyclization adduct, the derivation of complex natural molecules and the facile synthesis of polyamides highlight a diversity of synthetic potential of the current methodology.

Due to their transition metal‐like behavior divalent group 14 compounds bear huge potential for their application in bond activation reactions and catalysis. Here we report on detailed computational studies on the use of ylide‐substituted tetrylenes in the activation of dihydrogen and phenol. A series of acyclic and cyclic ylidyltetrylenes featuring various α‐substituents with different σ‐ and π‐donating capabilities have been investigated which demonstrate that particularly π‐accepting boryl groups lead to beneficial properties and low barriers for single‐site activation reactions, above all in the case of silylenes. In contrast, for the thermodynamically more stable germylenes and stannylenes an alternative mechanism involving the active participation of the ylide ligand in the E−H bond (E=H or PhO) activation process by addition across the element carbon linkage was found to be energetically favored. Furthermore, the boryl substituted tetrylenes allowed for a further activation pathway involving the active participation of the boron element bond. These cooperative mechanisms are especially attractive for the heavier cyclic ylidyltetrylenes in which the loss of the protonated ylide group is prevented due to the cyclic framework. Overall, the present studies suggest that cyclic ylide‐substituted germylenes and stannylenes bear huge potential for cooperative bond activations at mild conditions which should be experimentally addressed in the future.

Synthetic Applications of C–O and C–E Bond Activation Reactions