Ruthenium-catalyzed synthesis cyclization with alkynes

Direct C-H bond functionalization via ruthenium complexes catalysis has been well explored [5]. However, the rapid progress for heterocycle synthesis via ruthenium-catalyzed C-H activation has been only achieved since 2011. By utilizing the less expensive and stable ruthenium(II) complex [RuCl2(/ -cymene)]2, the oxidative cyclization reactions with a series of unsaturated small molecules like alkenes and alkynes proved to be a fast access to heterocycles. Herein, this chapter is intended to provide an overview of reported examples for ruthenium-catalyzed C-H bond activation and cyclization for heterocycle synthesis till the end of 2014, including mechanism presentations... 

Cycloaromatization of enediynes by diradical pathways in the thermal-and metal-catalyzed routes allows nonfunctionalized benzene derivatives to be prepared. The aromatization of enediynes by the action of nucleophiles produces aromatic compounds retaining the respective nucleophilic residue [333, 334]. The ruthenium-catalyzed reaction gives rise to the synthesis of various functionalized benzene derivatives. Thus, adding water, alcohols, aniline, acetylacetone, pyrroles, and dimethyl malonate to acyclic and aromatic enediynes 3.711 at 100°C for 12-24 hours in the presence of TpRuPPh3(MeCN)2PF6 (10 mol%) led to the functionalized benzenes 3.712 in satisfactory yields (Scheme 3.79) [334]. This cyclization involves regioselective nucleophilic attack of enediyne 3.711 to form a, TT-vinylruthenium intermediate 3.714 which finally converts to the benzene derivative. Experiment with labeled hydrogen atoms showed that the ruthenium n-alkyne complexes 3.713 are catalytically active. 

While application of the transition-metal-catalyzed [2 - - 2 - - 2] cycloaddition reaction and its variants for the construction of a benzene unit led to a plethora of natural products with different molecular structures and architectures, its use for the construction of a pyridine moiety within a natural product synthesis is less well developed. The reason for this is uncertain and should not account for the pyridine formation per se the co-cyclization of two alkynes with a nitrile unit to give a pyridine core can be catalyzed efficiently by cobalt, ruthenium, and cationic rhodium complexes, as shown in many methodology-oriented studies [35]. 

By introduction of an oxidizing directing group, Li and Wang demonstrated a regioselective ruthenium(ll)-catalyzed isoquinolone synthesis through oxidative cyclization of JV-methoxybenzamides with internal alkynes (Eq. (7.24)) [31]. This redox-neutral strategy circumvents the use of wasteful metal oxidants, and the reaction could take place at much milder conditions with broad substrate scope. 

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