Progress in palladium-based catalytic systems for the sustainable synthesis of annulated heterocycles: a focus on indole backbones

Abstract

A survey highlighting the most recent palladium catalytic systems produced and their performances for progress in direct synthesis of indole backbones by heterocarbocyclization of reactive substrates is provided. The discussion is developed in relation with the principles of sustainable chemistry concerning atom and mass economy. In this respect, the general convergent character of the syntheses is of particular interest (one-pot, domino, cascade or tandem reactions), and the substrates accessibility and reactivity, together with the final waste production, are also important. This critical review clearly indicates that the development of ligand chemistry, mainly phosphines and carbenes, in the last few decades gave a significant impetus to powerful functionalization of indoles at virtually all positions of this ubiquitous backbone (118 references).

A practical Cu(I)-catalyzed domino approach to 1,2-disubstituted indoles and its application for the assembly of indolophenanthridines

“…Initially, the domino synthesis of 3l was chosen as the model reaction. After stirring for 18 h under the Cu(I) catalysis, Pd(OAc) 2 , P(p-Tol) 3 and Cs 2 CO 3 were directly added to the reaction mixture without isolating intermediate 3l. We were pleased to find that the desired indolo[1,2-f]phenanthridine 4a was isolated in 85% yield (Scheme 3, entry 1).…”

“…3,4 Popular approaches to these heterocycles include N-modification of 2-substituted NH indoles, 5-7 2-arylation of N-substituted indoles, [8][9][10] coupling/annulation of o-haloanilines with alkynes, [11][12][13] and intramolecular cyclization of o-(gem-dihalovinyl)anilines. [14][15][16] Several one-pot synthetic protocols have also been developed recently.…”

Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst

“…Amongst the variety of heterocycles, indoles and benzofurans have emerged as privileged structures, especially in medicinal chemistry [1]. This great interest stimulated organic chemists to design efficient and diverse synthetic accesses, abundantly reviewed in the past few years [2–7]. A detailed survey of the recent literature revealed that both indoles and benzofurans can be attained by a cascade Sonogashira alkynylation–cyclization sequence (Scheme 1).…”

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

“…For several years, the development of methodologies concerning indole synthesis and functionalization has been one of the most attractive goals in organic chemistry [33–39]. In the search for clean and sustainable synthetic protocols suitable to construct and convert the indole core motif into more complex structures, palladium-based catalytic systems were proven to be fruitful tools for organic chemists [40–42]. …”