**7.1 Synthesis of** *pyrroles via* **C-H/N-H alkyne annulation**


## **7.2 Synthesis of 2-pyridones** *via* **C-H/N-H alkyne annulation**

In 2011, Ackermann and co-workers used a ruthenium catalyst to execute the C-H/N-H activation and oxidative alkyne annulation reaction to synthesize substituted 2-pyridones via C-C and C-N bond formation (**Figure 19**) [38]. They

**Figure 16.**

*Ruthenium(II)-catalyzed pyrrole synthesis* via *C-H/N-H alkyne annulation.*

#### **Figure 17.**

*Ruthenium-catalyzed pyrrole synthesis.*

#### **Figure 18.** *Cationic Ru(II)-catalyzed synthesis of* N*-acetylpyrroles.*

**Figure 19.** *Ruthenium(II)-catalyzed synthesis of 2-Pyridones.*

used various electron-rich and electron-deficient *N*-substituted acrylamides as well as diaryl- and dialkyl-substituted internal alkynes which shows a broad and improved range of substrate scope.

#### **7.3 Synthesis of indoles** *via* **C-H/N-H alkyne annulation**

i. In 2012, Ackermann and co-workers demonstrated an cationic Ru(II) catalyzed (generated *in situ*) oxidative C–H/N–H bond functionalizations of anilines using a removable directing group to synthesize various bioactive substituted indole derivatives (**Figure 20**) [39]. Herein, the oxidative alkyne annulation occurs through the construction of C-C and C-N bonds using water as the solvent. Mechanistic studies indicate that the reaction proceeds through the reversible formation of a six-membered ruthenacycles as the key intermediates.

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

**Figure 20.** *Cationic ruthenium(II)-catalyzed synthesis of indoles.*


## **7.4 Synthesis of Isoquinolines/Isoquinolones** *via* **C-H/N-H alkyne annulation**

i. In 2011, Ackermann *et al.* reported an unparalleled ruthenium(II) catalyzed annulations of alkynes using *N*-benzyl-substituted benzamides as the substrates and internal alkynes as the annulating partner. Here,

**Figure 21.** *Ruthenium(II)-catalyzed synthesis of indoles* via *N-N cleavage.*

**Figure 22.** *Ruthenium(II)-catalyzed electrochemical synthesis of indoles.*

chemo- and site-selective functionalization of both C-H and N-H bonds occurs during the synthesis of isoquinolone derivatives (**Figure 23**) [42]. Mechanistic studies in deuterated *<sup>t</sup>* AmOH suggests an irreversible C-H bond ruthenation. Further, the kinetic isotope effect (KIE) study provided strong evidence for a rate-limiting C-H bond ruthenation through carboxylate assistance.

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

**Figure 23.**

*Ruthenium(II)-catalyzed synthesis of Isoquinolones.*

**Figure 24.**

*Ruthenium(II)-catalyzed external oxidant free synthesis of Isoquinolones.*

**Figure 25.**

*Ruthenium catalyzed synthesis of Isoquinoline derivatives.*


**Figure 26.** *Ruthenium(II)-catalyzed external oxidant free synthesis of Isoquinolones.*

**Figure 27.** *Ru(II)-CatalyZed synthesis of 1-Aminoisoquinolines derivatives.*


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

**Figure 28.** *Ruthenium(II)-catalyzed synthesis of Isoquinolone derivatives.*

#### **Figure 29.**

*Ru(II)-catalyzed synthesis of Isoquinoline derivatives.*

achieve isoquinolones with high regioselectivity, broad substrate scope and broad functional group tolerance (**Figure 28**) [47]. The reaction occurs in the presence of [RuCl2(*p*-cymene)]2 as the catalyst and Cu(OAc)2H2O as an oxidant with the involvement of a monoacetate complex [RuCl(OAc) (*p*-cymene)] instead of the bis-acetate complex [Ru(OAc)2(*p*-cymene)]. The mechanistic studies reveals involvement of a ruthenium N-quinolin-8-yl- benzamide complex (i.e. N,N-bidentate chelate complex).

vii. In 2017, Gogoi *et al.* reported a Ru(II)-catalyzed C-H/N-H activation and oxidative annulation of benzamidines and internal alkynes for the facile synthesis of 1-aminoisoquinolines with excellent regioselectivity (**Figure 29**) [48].

viii. In 2017, Urriolabeitia *et al.* described a carboxylate assisted Ru(II) catalyzed synthesis of isoquinoline-1-carboxylate derivatives through C-H/N-H oxidative annulation reaction between *N*-unprotected methyl esters of phenylglycine and internal alkynes (**Figure 30**) [49]. The *N*-fluoro-2,4,6-trimethylpyridinium triflate works as the terminal oxidant and the process shows a remarkable tolerance to the presence of diverse electronreleasing and electron-donating functional groups at the phenyl ring of the amino acid.
