The Pd-catalyzed condensation of 2-bromostyrene and 2-chloroaniline derivatives yields stable diphenylamine intermediates, which are selectively converted to five-, six-, or seven-membered heteroaromatics (indoles, carbazoles, acridines, and dibenzazepines). The selectivity of these intramolecular transformations is uniquely ligand-controlled and offers efficient routes to four important classes of heterocycles from a common precursor.

Synthesis of Heterocycles via Pd-Ligand Controlled Cyclization of 2-Chloro-N-(2-vinyl)aniline: Preparation of Carbazoles, Indoles, Dibenzazepines and Acridines

An asymmetric intermolecular, three-component radical-initiated dicarbofunctionalization of 1,1-diarylalkenes with diverse carbon-centered radical precursors and electron-rich heteroaromatics by a copper(I) and chiral phosphoric acid cooperative catalysis strategy has been developed, providing straightforward access to chiral triarylmethanes bearing quaternary all-carbon stereocenters with high efficiency as well as excellent chemo- and enantioselectivity. The key to success is not only the introduction of a sterically demanding chiral phosphoric acid to favor radical difunctionalization over the otherwise remarkable side reactions but also the in situ generation of carbocation intermediates from benzylic radical to realize asymmetric induction with the aid of a removable hydroxy directing group via cooperative interactions with chiral phosphate. Density functional theory calculations elucidated the critical chiral environment created by the hydrogen-bonding and ion-pair interactions between the chiral phosphoric acid catalyst and substrates, which leads to the enantioselective C-C bond formation.

Cu/Chiral Phosphoric Acid-Catalyzed Asymmetric Three-Component Radical-Initiated 1,2-Dicarbofunctionalization of Alkenes.

In the pursuit of new pharmaceuticals and agrochemicals, chemists in the life science industry require access to mild and robust synthetic methodologies to systematically modify chemical structures, explore novel chemical space, and enable efficient synthesis. In this context, photocatalysis has emerged as a powerful technology for the synthesis of complex and often highly functionalized molecules. This Review aims to summarize the published contributions to the field from the life science industry, including research from industrial-academic partnerships. An overview of the synthetic methodologies developed and strategic applications in chemical synthesis, including peptide functionalization, isotope labeling, and both DNA-encoded and traditional library synthesis, is provided, along with a summary of the state-of-the-art in photoreactor technology and the effective upscaling of photocatalytic reactions.

Photocatalysis in the Life Science Industry.

Alkoxy radicals are highly reactive species that have long been recognized as versatile intermediates in organic synthesis. However, their development has long been impeded due to a lack of convenient methods for their generation. Thanks to advances in photoredox catalysis, enabling facile access to alkoxy radicals from bench-stable precursors and free alcohols under mild conditions, research interest in this field has been renewed. This review comprehensively summarizes the recent progress in alkoxy radical-mediated transformations under visible light irradiation. Elementary steps for alkoxy radical generation from either radical precursors or free alcohols are central to reaction development; thus, each section is categorized and discussed accordingly. Throughout this review, we have focused on the different mechanisms of alkoxy radical generation as well as their impact on synthetic utilizations. Notably, the catalytic generation of alkoxy radicals from abundant alcohols is still in the early stage, providing intriguing opportunities to exploit alkoxy radicals for diverse synthetic paradigms.

Alkoxy Radicals See the Light: New Paradigms of Photochemical Synthesis.

Transition metal-catalyzed directed C–H activation has emerged as an increasingly powerful tool for the synthesis of important organic building blocks, organic materials and natural products. Despite the great advances in the past decades, the majority of C–H functionalization systems focus on aryl C–H activation. Given the wide presence of alkenes as substrates, olefinic C–H functionalization, which is a step-economic process, is highly desirable for the construction of functional olefins. Herein, we summarize the recent advances during 2015–2020 in the field of metal-catalyzed olefinic C–H functionalization. This review is organized according to the metal center of the catalyst, with an emphasis on the similarities and differences among different catalysts in olefinic C–H functionalization.

Recent advances in transition metal-catalyzed olefinic C–H functionalization

This work has received financial support from Spanish grants (SAF2016-76689-R and CTQ2016-77047-P), the Xunta de Galicia (ED431C 2017/19, 2015-CP082 and Centro Singular de Investigacion de Galicia accreditation 2016-2019, ED431G/09) the European Regional Development Fund (ERDF), and the European Research Council (Advanced Grant No. 340055). The orfeo-cinqa network CTQ2016-81797-REDC is also kindly acknowledged

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Rhodium(III)-Catalyzed Annulation of 2-Alkenyl Anilides with Alkynes through C-H Activation: Direct Access to 2-Substituted Indolines.

Palladium-Catalyzed Formal (5 + 2) Annulation between ortho-Alkenylanilides and Allenes.

Enantioenriched, six-membered azacycles are essential structural motifs in many products of pharmaceutical or agrochemical interest. Here we report a simple and practical method for enantioselective assembly of tetrahydropyridines, which is paired to a kinetic resolution of α-branched allyltriflamides. The reaction consists of a formal (4+2) cycloaddition between the allylamine derivatives and allenes and is initiated by a palladium(II)-catalyzed C-H activation process. Both the chiral allylamide precursors and the tetrahydropyridine adducts were successfully obtained in high yields, with excellent enantioselectivity (up to 99% ee) and selectivity values of up to 127.

Kinetic Resolution of Allyltriflamides through a Pd-Catalyzed C-H Functionalization with Allenes: Asymmetric Assembly of Tetrahydropyridines

The first example of photocatalytic trifluoromethoxylation of arenes and heteroarenes under continuous-flow conditions is described. Application of continuous-flow microreactor technology allowed to reduce the residence time up to 16 times in comparison to the batch procedure, while achieving similar or higher yields. In addition, the use of inorganic bases was demonstrated to increase the reaction yield under batch conditions.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-16-111.pdf

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

We report a formal (4+2) cycloaddition between alkyl-nosylamides and dienes enabled by a palladium-catalyzed activation of C(sp3)–H bonds beta to the amide group. This atom economical reaction, whi...

/pdf/palladium-catalyzed-formal-4-2-cycloaddition-between-alkyl-koyu83syr2.pdf

Borja Cendón

Papers

Rhodium(III)-Catalyzed Annulation of 2-Alkenyl Anilides with Alkynes through C-H Activation: Direct Access to 2-Substituted Indolines.

Palladium-Catalyzed Formal (5 + 2) Annulation between ortho-Alkenylanilides and Allenes.

Kinetic Resolution of Allyltriflamides through a Pd-Catalyzed C-H Functionalization with Allenes: Asymmetric Assembly of Tetrahydropyridines

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

Palladium-Catalyzed Formal (4+2) Cycloaddition between Alkyl Amides and Dienes Initiated by the Activation of C(sp3)−H Bonds