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A cascade approach has been developed towards dual C-C bond formation via consecutive C-H functionalization/cyclization giving access to pyrrolo[1,2-a]indoles in a highly regio- and diastereoselective manner using catalytic [Ru(p-cymene)Cl 2 ] 2 . The methodology was further expanded to attain pentacyclic structures involving manifold C-C bond creation.

Pd-catalyzed domino Heck/borylation of acrylamides with B2pin2 is reported to generate synthetically useful indolinone-3-methyl boronic esters, via capturing σ-alkyl palladium with boron. Further functionalization of the obtained boronic ester qualify it as a new starting point for the functionalization of specific C(sp(3))-H bond. Moreover, the application of an Ugi-adduct as starting material or B2nep2 as an alternative boron source works equally well, making this a broadly applicable and robust method for the formation of a C-C and C-B bond in a single operation.

The Ugi-4CR is by far one of the most successful multicomponent reactions leading to high structural diversity and molecular complexity. However, the reaction mostly affords a linear peptide backbone, enabling post-Ugi transformations as the only solution to rigidify the Ugi-adduct into more drug like species. Not surprisingly, the development of these transformations, leading to new structural frameworks, has expanded rapidly over the last few years. As expected, palladium-catalyzed reactions have received the foremost attention, yet other metals, particularly gold complexes, are fast catching up. This tutorial review outlines the developments achieved in the past decade, highlighting the modifications that are performed in a sequential or domino fashion with emphasis on major concepts, synthetic applications of the derived products as well as mechanistic aspects.

The tuning of selective ring closure is a nontrivial challenge in synthetic organic chemistry. Herein we report a solvent switchable metal-free [4 + 2] cycloaddition approach via Csp(2)-H functionalization. The protocol is highly atom economical with water being the only by-product, delivering N-substituted benzo[e]- or [f]isoindolones in high yields.

An Ugi four-component reaction of propargylamine with 3-formylindole and various acids and isonitriles produces adducts which are subjected to a cationic gold-catalyzed diastereoselective domino cyclization to furnish diversely substituted spiroindolines. All the reactions run via an exo-dig attack in the hydroarylation step followed by an intramolecular diastereoselective trapping of the imminium ion. The whole sequence is atom economic and the application of a multicomponent reaction assures diversity.

A gold-catalyzed regioselective tandem cyclization of N-propynylbutynamide via Csp(3)-H functionalization has been described, providing a distinctive methodology for the architecture of cyclopentapyridinones as well as spirocyclopentapyridinones.

Coupling the strangers: A copper-catalyzed three-component heteroarene-amine-aldehyde/ketone coupling affords a novel approach to the hitherto difficult direct secondary/tertiary C-H alkylation of azoles. This simple method allows the facile installation of diversely substituted, branched and nitrogen-containing alkyl or alkaloid side chains on the azole moiety by using readily available starting materials., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A regioselective approach for the synthesis of pyrrolopyridinones and pyrroloazepinones is reported employing an Ugi reaction followed by a gold(I) or platinum(II) catalyzed intramolecular hydroarylation.

The direct C-H arylation of 1,3,4-thiadiazoles with a wide range of (hetero)aryl iodides, bromides, and triflates is described using a Pd/Cu-catalyzed protocol. The methodology is compatible with substrates possessing electron-donating or electron-withdrawing substituents and also tolerates sterically hindered aryl halides. The utility of the developed protocol is demonstrated by a one-pot C-H arylation-Suzuki coupling sequence.

A diversity oriented approach for the synthesis of indoloazocines is reported employing an Ugi reaction followed by a gold-catalyzed intramolecular hydroarylation.