**Abstract**

In last few decades, the transition metal-catalyzed C-H bond activation and alkyne annulation reactions have turned out to be effective methods for the construction of highly important heterocycles. In particular, the Ru(II) catalysts have been used for the oxidative coupling between an internal alkynes and readily available nitrogen directed compounds in a rapid and sustainable manner. The Ru (II) catalysts are very much beneficial due to their stability in both air and water, ease of preparation, inexpensive than those of Rh(III) and designer Co(III) catalysts usually used for alkyne annulation reactions, requirement of mild reaction conditions, and compatible with various oxidants. Owing to these advantages of Ru(II) catalysts herein, we attempt to highlight the recent development in C-H activation and annulation reactions, which lead to the formation of several important *N*-heterocycles.

**Keywords:** Ru(II)-catalysts, C-H activation, alkyne annulation, *N*-heterocycles

### **1. Introduction**

The development of highly efficient methods for the synthesis of *N*-heterocyclic skeletons is one of the important targets in organic synthesis. This is because, the nitrogen-containing heterocycles represents a significant class of organic substances, which are particularly found in various biologically active compounds, natural products, drugs, and other medicinally related compounds [1–10]. The *N*-heterocycles especially, pyrroles [2], pyridines/pyridinos [3, 4], indoles [5], isoquinolines [6], quinozalines/quinolizines [7, 8] are useful building blocks of many biologically as well as pharmaceutically active molecules, constitute the core motif of many natural products, and also found wide application in the field of materials science. Due to photo and electrochemical properties highly substituted π-conjugated fused polycyclic *N*-heterocyclic compounds are extensively used as organic semiconductors or luminescent materials [9]. Furthermore, some of these polycyclic *N*-heteroarenes derivatives are versatile building blocks for various natural products [10]. Consequently, in the light of their importance, a large number of efficient methods have been developed, among which the transition metal [Rh(III), Co(III), Ru(II), Pd(II), Ni(II)/Ni(0)]-catalyzed C-H bond activation and oxidative

alkyne annulation reactions are serving as most attractive methodologies, for the construction of *N*-heterocycles [11–16]. The *ortho*-C-H bond activation *via* the use of coordinative functional group followed by cyclization with internal alkynes, commonly known as annulation reaction is extremely motivating as it allows the formation of highly important heterocycles in an atom economical fashion. In this context, the Ru(II) catalysts have been used extensively for the catalytic activation of unreactive C-H bonds and oxidative annulation reactions, particularly with internal alkynes. This is due to several advantages of Ru(II) catalyst such as both air and water stability, easy to prepare, mild reaction conditions, compatible with various oxidants, relatively cheaper and provides excellent chemo- and regioselective functionalizations than those of Rh(III) and Co(III) catalysts. In this chapter, we attempt to highlight the progresses in the field of C-H bond activation catalyzed by Ru(II) complexes leading to the construction of various *N*-heterocycles via oxidative alkyne annulation reactions.

### **2. The ruthenium(II) catalyst**

For C-H bond activation and oxidative alkyne annulation reactions, the commonly used ruthenium(II) catalyst is dichloro(*p*-cymene)ruthenium(II) dimer, [Ru(*p*-cymene)Cl2]2. This dimeric Ru(II) catalyst in combination with acetate/carbonate bases or acetate containing oxidants Cu(OAC)2∙H2O generates the active species *via* ligand exchange which is responsible for the deprotonative C-H or C-H/N-H activation. In the presence of other oxidants such as AgSbF6 or KPF6, the dimeric Ru(II) complex forms an active cationic species either in the absence or presence of Cu(OAC)2∙H2O. Again, the oxidants are necessary to reoxidize the Ru (0) to Ru(II) after the reductive elimination to regenerate the active catalyst. The various combination of reagents with Ru(II) dimeric complex for the *in situ* generation of active Ru(II) catalyst in the C-H bond activation and oxidative alkyne annulation processes are shown in **Figure 1**.

**Figure 1.** In Situ *generated active Ru(II) complex.*

### **3. Ruthenium(II)-catalyzed C-H bond activation**

In the past few decades, Ru(II)-catalyzed C-H bond activation has become much popular for the C-C cross coupling reactions. In particular, the directing group assisted (chelation-assisted) C–H bond activation using coordinative functional

*Access to* N*-Heterocyclic Molecules* via *Ru(II)-Catalyzed Oxidative Alkyne… DOI: http://dx.doi.org/10.5772/intechopen.95987*

**Figure 2.** *Ru(II)-catalyzed C-H bond activation for the construction of C-C bond.*

group has offered several advantages [17]. Actually this activation strategy uses the proximate effect by coordination of a functional group in a given substrate to the ruthenium centre of the catalyst that brings about regioselective C-H bond activation and functionalization. In the processes of C-H bond activation reactions, the active Ru(II) catalysts facilitates the deprotonation of C-H bonds, before any oxidative addition and the process occur via the assistance of Ru(II) site and *in situ* coordinated carbonate [18] or carboxylate [19]. Alternatively, an intermolecular deprotonation of C-H bonds by carboxylate activates the Ru(II) [20] thereby forming a C Ru species, which is the key intermediate in the coupling reactions (**Figure 2**).
