Towards Rare-Functionalized N-Alkenyl-1H-pyrroles via Regioselectively Metalated N-Isopropenyl-1H-pyrroles

Deprotonative metalation of N-isopropenyl-1H-pyrroles with superbases followed by trapping with a variety of electrophiles was studied as an effective tool for the regioselective functionalization of 1H-pyrroles

Regioselective Functionalization of Quinolines through C-H Activation: A Comprehensive Review

Quinoline is a versatile heterocycle that is part of numerous natural products and countless drugs. During the last decades, this scaffold also became widely used as ligand in organometallic catalysis. Therefore, access to functionalized quinolines is of great importance and continuous efforts have been made to develop efficient and regioselective synthetic methods. In this regard, C-H functionalization through transition metal catalysis, which is nowadays the Graal of organic green chemistry, represents the most attractive strategy. We aim herein at providing a comprehensive review of methods that allow site-selective metal-catalyzed C-H functionalization of quinolines, or their quinoline N-oxides counterparts, with a specific focus on their scope and limitations, as well as mechanistic aspects if that accounts for the selectivity.

Programmable Self-Assembly of Gold Nanoarrows via Regioselective Adsorption

Programing the self-assembly of colloidal nanoparticles into predetermined superstructures represents an attractive strategy to realize functional assemblies and novel nanodevices, but it remains a challenge. Herein, gold nanoarrows (GNAs) showing a distinct convex-concave structure were employed as unique building blocks for programmable self-assembly involving multiple assembly modes. Regioselective adsorption of 1,10-decanedithiol on the vertexes, edges, and facets of GNAs allowed for programmable self-assembly of GNAs with five distinct assembly modes, and regioselective blocking with 1-dodecanethiol followed by adsorption of 1,10-decanedithiol gave rise to programmable self-assembly with six assembly modes including three novel wing-engaged modes. The assembly mode was essentially determined by regioselective adsorption of the dithiol linker dictated by the local curvature together with the shape complementarity of GNAs. This approach reveals how the geometric morphology of nanoparticles affects their regioselective functionalization and drives their self-assembly.

Desymmetrization of Pibrentasvir for Efficient Prodrug Synthesis

A novel and practical desymmetrization tactic is described to access a new class of pibrentasvir prodrugs. The homotopic benzimidazoles of pibrentasvir (PIB) are differentiated via a one-pot di-Boc/mono-de-Boc selective <i>N</i>-Boc protection and formaldehyde adduct formation sequence, both enabled by crystallization-induced selectivity. The first step represents the only known application of the Horeau principle of statistical amplification for <i>C</i>₂-symmetric polyheterocycle regioselective functionalization. The resulting versatile intermediate is employed in the high-yielding preparation of several pibrentasvir prodrug candidates.

Desymmetrization of Pibrentasvir for Efficient Prodrug Synthesis

A novel and practical desymmetrization tactic is described to access a new class of pibrentasvir prodrugs. The homotopic benzimidazoles of pibrentasvir (PIB) are differentiated via a one-pot di-Boc/mono-de-Boc selective <i>N</i>-Boc protection and formaldehyde adduct formation sequence, both enabled by crystallization-induced selectivity. The first step represents the only known application of the Horeau principle of statistical amplification for <i>C</i>₂-symmetric polyheterocycle regioselective functionalization. The resulting versatile intermediate is employed in the high-yielding preparation of several pibrentasvir prodrug candidates.

Radical Trifluoroacetylation of Alkenes Triggered by a Visible-Light-Promoted C−O Bond Fragmentation of Trifluoroacetic Anhydride

Trifluoromethyl ketones are not only found in drug like substances, but are also considered as key synthons for the preparation of various fluorinated heterocyclic molecules. Access to such trifluoromethyl ketone derivatives typically requires the incorporation of the trifluoromethyl group, or a surrogate moiety, at the beginning of a multi-step synthetic sequence. However, direct trifluoroacylation of alkenes could potentially provide a highly efficient and straightforward method for the synthesis of a,b-unsaturated trifluoromethyl ketones. Here we report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low-cost and readily available reagent. This light-mediated process is fundamentally different from conventional methodologies and occurs through an trifluoroacyl radical mechanism promoted by a photocatalyst. Beyond simple alkenes, this method allows for chemo- and regioselective functionalization of small-molecule drugs and common pharmacophores.

Radical Trifluoroacetylation of Alkenes Triggered by a Visible-Light-Promoted C−O Bond Fragmentation of Trifluoroacetic Anhydride

Trifluoromethyl ketones are not only found in drug like substances, but are also considered as key synthons for the preparation of various fluorinated heterocyclic molecules. Access to such trifluoromethyl ketone derivatives typically requires the incorporation of the trifluoromethyl group, or a surrogate moiety, at the beginning of a multi-step synthetic sequence. However, direct trifluoroacylation of alkenes could potentially provide a highly efficient and straightforward method for the synthesis of a,b-unsaturated trifluoromethyl ketones. Here we report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low-cost and readily available reagent. This light-mediated process is fundamentally different from conventional methodologies and occurs through an trifluoroacyl radical mechanism promoted by a photocatalyst. Beyond simple alkenes, this method allows for chemo- and regioselective functionalization of small-molecule drugs and common pharmacophores.