Ruthenium-catalysed one-pot regio- and diastereoselective synthesis of pyrrolo[1,2-a]indoles via cascade C-H functionalization/annulation.

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)Cl2]2. The methodology was further expanded to attain pentacyclic structures involving manifold C-C bond creation.

Domino Heck/borylation sequence towards indolinone-3-methyl boronic esters: trapping of the σ-alkylpalladium intermediate with boron.

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.

Metal-mediated post-Ugi transformations for the construction of diverse heterocyclic scaffolds.

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.

Solvent switchable cycloaddition: a (one-pot) metal-free approach towards N-substituted benzo[e]- or [f]isoindolones via C(sp(2))-H functionalization.

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.

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines.

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.

Synthesis of (spiro)cyclopentapyridinones via C(sp3)-H functionalization: a post-Ugi gold-catalyzed regioselective tandem cyclization.

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.

Copper-catalyzed direct secondary and tertiary C-H alkylation of azoles through a heteroarene-amine-aldehyde/ketone coupling reaction.

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.

Gold(I) and platinum(II) switch: a post-Ugi intramolecular hydroarylation to pyrrolopyridinones and pyrroloazepinones.

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.

Pd/Cu-catalyzed C-H arylation of 1,3,4-thiadiazoles with (hetero)aryl iodides, bromides, and triflates.

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 concise route to indoloazocines via a sequential Ugi-gold-catalyzed intramolecular hydroarylation.

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