MRV

Herein, we report the first nickel-catalyzed dearomative dialkylation of indoles with two distinct alkyl halides via three component cross-electrophile coupling under mild conditions. The catalytic protocol offers a route for the modular assembly of diverse carbon quaternary center-containing dialkylated indoline derivatives with a broad substrate scope, great functional group tolerance and high chemo- and diastereoselectivities.

Abstract

The catalytic dearomative dicarbofunctionalization of indoles constitutes one of the most efficient ways to access poly-substituted indolines that are prevalent in many natural products and drugs. However, despite significant advances, three component dearomative dicarbofunctionalization of indoles has remained elusive. Herein, we report an unprecedented nickel-catalyzed dearomative dialkylation of indoles with two different alkyl halides via three component cross-electrophile coupling under mild conditions with the construction of two vicinal C(sp³)─C(sp³) bonds at C2 and C3 sites. The catalytic protocol offers an efficient and straightforward route for the modular assembly of diverse carbon quaternary center-containing dialkylated indoline derivatives with a broad substrate scope (75 examples), excellent functional group tolerance and high chemo- and diastereoselectivities. Mechanistic studies, combining a series of experiments and DFT calculations, reveal that the catalytic reaction proceeds via a radical pathway.

Combining enantioselective catalysis with photocatalysis in flow platforms enables efficient, selective, and scalable transformations. While this merger addresses key limitations of batch protocols, it also introduces new challenges specific to the integration of these methodologies. Recent studies underline both the promise and the need for refined strategies to fully exploit this approach.

The integration of asymmetric catalysis, crucial for the synthesis of structurally complex and enantioenriched target molecules, with photocatalysis, renowned for its atom economy and operational simplicity, offers a synergistic platform with considerable potential. Incorporating this dual strategy into flow systems further enhances the overall efficiency, enabling improved reaction control, scalability, and sustainability. This review provides an overview of recent advancements and discoveries that demonstrate the advantages of this merger, despite its relatively unexplored nature. The advancement of these processes together may uncover new possibilities in catalytic processes.

Synlett
DOI: 10.1055/a-2710-2644

The asymmetric 1,2-difunctionalization of alkenes stands as one of the swiftest approaches to turn ubiquitous C(sp2)-feedstocks into C(sp3)-rich chiral fine chemicals. State-of-the-art transition metal-catalyzed protocols are efficient, selective, and robust; however, they are often limited in alkene scope, functional group tolerance, and are only applicable to specialized systems. Recently, the use of synthetic electrochemistry has provided effective solutions to these challenges, fostering the development of more general, selective, and sustainable variants. In this Synpacts, we will survey selected literature examples showcasing how electrosynthetic tools have been instrumental in enabling the design of innovative diastereo- and enantioselective alkene 1,2-difunctionalization reactions. These seminal contributions have inspired us to conceive a complementary “Sew & Cut” strategy—combining the generality and selectivity of pericyclic 1,3-dipolar cycloadditions with the complexity-generating ability of radical reactivity.
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Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

A synergistic dual chiral primary amine and naphthalene catalysis was identified through enamine-redox mediator mapping (e-RM²) to enable effective electrochemical singly occupied molecular orbital (SOMO)-type coupling with alkenyl trifluoroborate. Mechanistic studies reveal ion-pair interactions between the protonated aminocatalyst and anionic substrate, leading to exceptional enantioselectivity.

Abstract

External tuning of enamine intermediate has significantly expanded reaction space of typical aminocatalysis. Notwithstanding the progress of chemo- and photo-oxidation of enamine intermediate, electro-oxidation was left as a much less explored area, in stark contrast to the prosperous renaissance of electrochemistry in recent years. Challenges mainly come from the reactivity barrier as a consequence of heterogeneous electron transfer and subtle stereocontrol in ionic electrolyte solution under the influence of electric field. Herein, we report asymmetric α-alkenylation of carbonyl compounds using potassium alkenyl trifluoroborate as a model reaction to demonstrate the capability of primary amine catalysis under electrochemical conditions. By employing enamine redox mediator mapping (e-RM²) strategy, a new organic mediator, dimethoxyl naphthalene, was found to greatly enhance reactivity. Mechanistic studies uncover an ion-pair interaction between protonated aminocatalyst and anionic substrate that accounts for the exceptional enantioselectivity. This catalytic system demonstrates the best level of enantioselectivities in electro-oxidative enamine transformations so far.