Thiourea‐Catalyzed Asymmetric Michael Addition of Carbazolones to 2‐Chloroacrylonitrile: Total Synthesis of 5,22‐Dioxokopsane, Kopsinidine C, and Demethoxycarbonylkopsin

Over the past decades, aspidosperma and kopsia alkaloids have attracted significant interest by the organic synthetic community owing to their intricate fused‐ring structures and broad biological activities. Consequently, numerous strategically distinct total syntheses have been accomplished, among which tetracyclic pyridocarbazoles have seen widespread adoption as versatile building blocks. In this review, we elaborate and discuss the synthesis of such tetracyclic pyridocarbazoles according to the different approaches for the establishment of the all‐carbon quaternary center at C5. This includes (1) classic synthetic reactions (cycloaddition, Michael addition, nucleophilic substitution, and Claisen rearrangement), (2) palladium‐catalyzed asymmetric decarboxylative allylation reactions, and (3) thiourea‐catalyzed asymmetric Michael addition reactions. Furthermore, we also describe the late‐stage key transformations in the realm of the total syntheses of aspidosperma and kopsia alkaloids.

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Recent Advances in the Total Synthesis of Aspidosperma and Kopsia Alkaloids Using Tetracyclic Pyridocarbazoles as Versatile Building Blocks

Wang

Xiao

Liu

et al. 2022

Adv Synth Catal

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Multifaceted Domino Knoevenagel‐Cyclization Reactions; Four Movements for 2H‐Chromenes and Chromans

et al. 2023

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Domino Knoevenagel‐cyclization reactions of 2H‐chromene and chroman derivatives containing o‐formylaryl amine or ether side‐chain was carried out to produce four series of chiral condensed heterocycles representing four novel skeletons and exhibiting antiproliferative activity. The cyclization step occurred with four different mechanisms: a concerted intramolecular hetero Diels‐Alder reaction (IMHDA), a stepwise polar [2+2] cycloaddition, a [1,5]‐hydride shift‐6‐endo cyclization or a multi‐step nitro hetero Diels‐Alder‐ring‐opening‐Cadogan‐type cyclization sequence. The latter reaction provided a new route to hydroxyindoles by an inverse Cadogan‐type cyclization, in which the nitro group is deoxygenated by a nitro IMHDA‐ring‐opening sequence. The cyclization mechanisms and their stereoselectivity were studied by DFT calculations, based on which we proposed a mechanism for the multi‐step cyclization to hydroxyindoles and explained the observed diastereoselectivity.magnified image

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Pd‐Catalyzed Amidation of Silyl Enol Ethers With CO and Azides via an Isocyanate Intermediate

Jiang

Chen

et al. 2021

Asian J Org Chem

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An efficient Pd-catalyzed amidation of silyl enol ethers to produce β-ketoamides has been developed using carbon monoxide and sulfonyl azides. The tandem reaction provides a simple and straightforward approach for the synthesis of β-ketoamides under mild conditions without any additive. The mechanistic studies indicate that the reaction undergoes via an in situ generated isocyanate intermediate.The β-ketoamides are one of the most useful and synthetic building blocks in organic chemistry, which have been used for the synthesis of fungicides, penicillins, organic dyes and other biologically compounds. [1] Furthermore, the β-ketoamide skeletons are widely found in pharmaceutical molecules, such as Lymecycline, Teriflunomide, etc (Scheme 1a). [2] Given the importance and wide utilization of β-ketoamides, several notable approaches have been developed to synthesize β-ketoamides, including aminolysis of β-ketoesters, [3] α-acylation of amides, [4] addition of enolates to isocyanates [5] etc. However, these traditional methods are limited to one or more of the following elements, narrow substrate ranges, harsh reaction conditions, or using unfriendly reagents. Therefore, the development of simple, straightforward, and efficient catalytic methods for the synthesis of β-ketoamides is still highly desirable.Isocyanates are particularly useful in organic synthesis. [6] As a highly reactive intermediate, isocyanate has been extensively utilized for the synthesis of various nitrogen-containing compounds, such as ureas, [7] oxazolidinones, [8] and lactams,. [9] It has also been widely used as amide precursors in organic synthesis. [10] However, the high reactivity of isocyanates makes[a] Y.

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Thiourea‐Catalyzed Asymmetric Michael Addition of Carbazolones to 2‐Chloroacrylonitrile: Total Synthesis of 5,22‐Dioxokopsane, Kopsinidine C, and Demethoxycarbonylkopsin

Cited by 21 publications

References 76 publications

Recent Advances in the Total Synthesis of Aspidosperma and Kopsia Alkaloids Using Tetracyclic Pyridocarbazoles as Versatile Building Blocks

Recent Advances in the Total Synthesis of Aspidosperma and Kopsia Alkaloids Using Tetracyclic Pyridocarbazoles as Versatile Building Blocks

Multifaceted Domino Knoevenagel‐Cyclization Reactions; Four Movements for 2H‐Chromenes and Chromans

Pd‐Catalyzed Amidation of Silyl Enol Ethers With CO and Azides via an Isocyanate Intermediate

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