Recent Advances in the Interrupted Nazarov Reaction

Abstract

In recent decades there have been significant improvements in the efficiency of synthesis as a result of considerable progress in tandem reactions, cascade transformations and related one‐pot processes. These methodologies are less time‐consuming, more cost‐effective, and produce less waste compared to the classical stepwise protocols. The Nazarov cyclization is an important and versatile method for the synthesis of five‐membered carbocycles which are found in many natural compounds and functional molecules. Current activities in the field of the Nazarov reaction are focused on development of better catalysts, asymmetric options and increasing the efficiency of synthesis. This transformation is suitable for applying to an intensified step‐economy in interrupted versions and one‐pot protocols. Interrupted Nazarov reactions in particular take advantage of the stereospecific nature of the electrocyclization. The universality of these reactions has facilitated an access to a plethora of complex small molecules of high medicinal relevance. In this review, we present a comprehensive summary of recent advances in the interrupted Nazarov‐type cyclization, and classify these reactions according to the structure of the substrate or the reaction mechanism. This is the first review that presents a survey on various types of interrupted Nazarov cyclization and deals with the recent advances, especially using tandem/domino or one‐pot reaction strategies and covers the literature from 2009 to 2019.

Cyclization Strategies for the Concurrent Installation of Multiple Quaternary Stereogenic Centers

“…Additionally, the nucleophilic interruption by a carbon nucleophile (alkenes, enols/enolates, enamines, arenes, etc.) at C2 or C4 of cation 142 also enables the formation of a QSC at either of these two carbons, as can be seen in products 144 [80–84] …”

Transition Metal/Lewis Acid Catalyzed Reactions of Zerumbone for Diverse Molecular Motifs

“…The classical interrupted Nazarov reaction involves the electrocyclization of divinyl ketone providing the cyclopentenyl (oxyallyl) cation, later the addition of nucleophile afford the substituted cyclopentanones. The first step is the formation of the cyclopentenyl cation with the nucleophile, forming a mono‐addition product [70] . The scope of the interrupted Nazarov cyclisation with various substituted indoles afforded [5.8] fused‐ring systems in moderate to good yields.…”

“…The first step is the formation of the cyclopentenyl cation with the nucleophile, forming a mono-addition product. [70] The scope of the interrupted Nazarov cyclisation with various substituted indoles afforded [5.8] fused-ring systems in moderate to good yields. The mechanism of formation of isodaucane was initiated by the coordination of Lewis acid to the unactivated double bond and formation of a.…”

Novel d-Annulated Pentacyclic Steroids: Regioselective Synthesis and Biological Evaluation in Breast Cancer Cells

“…The Nazarov cyclization reaction represents one of the most effective methods for the construction of five-membered carbocyclic rings, and it has been applied in the total synthesis of many useful natural products. Due to high stereoselectivity, high yields, and readily available starting compounds, this reaction is widely used in organic synthesis for the preparation of diverse biologically active substances [ 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ]. However, to the best of our knowledge, this reaction was not applied for the annulation of an additional cyclopentanone ring onto the steroid skeleton.…”