Preparation of the Core Structure of<i>Aspidosperma</i>and<i>Strychnos</i>Alkaloids from Aryl Azides by a Cascade Radical Cyclization

Lin

et al. 2018

Chemistry A European J

Ynamides, as versatile synthetic precursors, have attracted much attention from synthetic chemists and sparked the development of a number of methodologies for the construction of various structures. 1H-Pyrrolo[2,3-d]carbazole is a core scaffold of a series of monoterpene indole alkaloids found in Kopsia, Strychnos, and Aspidosperma, for example. In this study, 1H-pyrrolo[2,3-d]carbazole derivatives were synthesized by a Brønsted acid-catalyzed tandem cyclization starting from tryptamine-based ynamides. This strategy prevented Wagner-Meerwein rearrangement by instantaneous intramolecular nucleophilic trapping of the indoleninium to afford a tetracyclic indoline via an in situ-formed enol species induced by the formation of a more stable conjugate diene moiety. The functional group tolerances were investigated by using a series of readily available substrates. A plausible mechanism has been proposed based on the evidence of the capture of the hemiaminal intermediate. Lastly, a Büchi ketone, which is the pivotal intermediate in the synthesis of the indole alkaloid vindorosine, was synthesized by utilizing our newly developed methodology.

Section: Introductionmentioning

confidence: 99%

Brønsted Acid‐Catalyzed Tandem Cyclizations of Tryptamine‐Ynamides Yielding 1H‐Pyrrolo[2,3‐d]carbazole Derivatives

Lin

et al. 2018

Chemistry A European J

“…In 2016, Renaud and co-workersr eported as imilar radical cyclization to the synthesis of tetracyclic indoline 134. [44] As depicted in Scheme 16, the cascade is triggered with the formation of stabilized a-amider adical 135,e nded up with trapping of the radicali ntermediate 136 by an aryl azide to build the tetracyclic indoline ring system 134.T hus the tetracyclic frame-work 134 was obtained by two consecutive 5-exo-trig radical cyclizations.…”

Section: Radical Cyclizationsmentioning

confidence: 99%

“…Scheme16. Consecutive 5-exo-trig radicalcyclizationst otetracyclic indoline 134 (Renaud et al [44] ). condensation between aniline 147 and acid 148.A fter some functional group manipulations, the key intermediate 152 was obtained.W ith the tricyclics pirodienone 152 in hand, an aza-Michael addition reactionw as carried out to afford the tricyclic indoline 154 by am ono Michael addition and tetracyclic indoline 155 via ad ouble Michael addition.…”

Section: Palladium-catalyzed Coupling Reactionsmentioning

confidence: 99%

Synthetic Approaches to Tetracyclic Indolines as Versatile Building Blocks of Diverse Indole Alkaloids

Xie

Lin

et al. 2018

Chemistry A European J

Indole alkaloids bearing the tetracyclic indoline scaffolds of 1H-pyrrolo[2,3-d]carbazole have shown fascinating chemical diversity and significant biological activities. The development of efficient synthetic methodologies for such a tetracyclic scaffold remains highly desirable in both synthetic chemistry and medicinal chemistry. This review outlines key strategies for the construction of the tetracyclic indoline scaffolds in total syntheses of many indole alkaloids. The key strategies include nucleophilic additions, Diels-Alder reactions, radical cyclizations, and palladium-catalyzed coupling reactions. The representative examples and their applications in the total syntheses are described here and discussed in depth.

“…Renaud group [41] reported a mild and novel approach toward the synthesis of aspidosperma and strychnos alkaloids via cascade radical cyclization reaction (Scheme-XIX). This sequence is based on the formation of quaternary carbon center of 70 through cyclization cascade process, followed by reaction with aryl azide radical intermediate, furnishing the 5-membered ring of the pyrrolocarbazole framework.…”

Section: Scheme-iv: Visible-light Induced C-h Functioalization Protocmentioning

confidence: 99%

Recent Free-Radical Reactions

Khalid¹,

Mohammed²

2018

Asian J. Chem.

Free radical reactions are one of the most coveted simulated objectives has been increasingly popular, very versatile and very important method in organic synthesis and due to their considerable and precious applications in different fields are widely used in the past few years. Free radical reactions can be efficient in the preparation of a large number of organic compounds which has been found large applications in many areas of life due to the ease of use of this method, accuracy, selectivity and required mild condition. Free radical reactions have many types of reaction e.g., cyclization, decarboxylation, additions reactions, hydrogen atom abstractions and alkynylation etc. [1a]. Free radicals are very supportive for the synthesis of cycles, atomic relocating permit effective groups to combine and facilely used to generate a number of ligations in one step [1b]. Likewise, the improvement of radicalmediated, C-C bond-forming transmutation has also attracted increasing attention. Usually, these protocols tolerate good selectivity, are highly convenient with collective functional This review highlights the most recent syntheses of free radical reactions, which included numerous processes (photoredox catalysis freeradical reactions, free-radical cascade processes reactions, Minisci-type free radical alkylation reactions and metal-catalysis free radical reactions). A photoredox-catalyzed C-H functioning of aromatic heterocyclic utilizing an assortment of various, alkyltrifluoroborates has been mentioned. Utilizing organo-photocatalyst and a moderate oxidant, conditions malleable for functionalizing complex aromatic heterocyclics are outlined to prepare a oriental agent for late-stage derivatization. Radical alkylations of aromatic heterocyclic (Minisci reactions) appear a more direct functionalization of particular, C-H bonds. For the ground mentioned above, alkylation designing using radical have recently risen to significance for the late-stage functionalization of aromatic heterocyclic framework. Therefore, this issue is the primary point of the present survey, which thinks about work from the most recent five years. The work is ordered by the key procedures associated with the synthesis of free-radical reactions, planning to give researchers a simple comprehension of this free radical-reactions-based science and to give bits of knowledge to provide insights for further investigations.