Diastereoselective Synthesis of Spirocyclopropane‐Linked Pyrazolones from Azomethine Ylides via C(sp³)‐H Activation

Abstract

A novel synthesis of spirocyclopropane‐1,4′‐pyrazolin‐5′‐one derivatives via iodine‐mediated C(sp3)–H activation is described. Thus, a diastereoselective synthesis of spirocyclopropane‐linked pyrazolones from 4‐arylidene‐3‐methyl‐1‐phenylpyrazolin‐5‐ones and azomethine ylides, generated in situ from iodine‐catalyzed reaction of 2‐methylquinoline or acetophenones with pyridine in the presence of base, has been developed. These transformations proceeded via a cyclopropanation reaction followed by anti‐elimination of pyridine. Unequivocal evidence for the structures of spirocycles rac‐anti‐5 a and rac‐anti‐12 a were obtained from single‐crystal X‐ray analyses. These methods offer several advantages, such as being inexpensive, moderate to high yield, high atom economy, and ease of product isolation, which make them attractive processes for the synthesis of spirocyclopropane‐linked pyrazolones. The spirans reported in this work may deserve further attention not only from a synthetic but also from a pharmacological point of view.

Sulfide‐Catalyzed Diastereoselective Spirocyclopropanation: Constructing Spiro‐cyclopropanyl‐pyrazolones From α‐Arylidenepyrazolones

“…Representative synthetic strategies toward these spiro skeletons include intramolecular cyclization, [4a,b,g] [2+1] annulation reaction, [4e,k] cascade reaction [4h,j,l–n] . In this context, annulation reactions of arylidenepyrazolones with chlorides, [3f,5] ammonium ylides [4i,6] and arsonium ylide [7] provided classical approaches (Scheme 1). Although impressive results have been achieved in synthesis of spirocyclopropanyl pyrazolone derivatives, it is still highly desirable to develop general and efficient process to benefit the synthesis of this spiro skeleton.…”

Synthesis of spiroindolo[2,1‐b]quinazolines from Huisgen zwitterions and tryptanthrin‐malononitrile adducts

“…As part of our studies on the synthesis of spirans, herein, we report an efficient synthesis of a novel series of functionalized spiroindolo[2,1‐ b ]quinazolines via 1,4‐dipolar cycloaddition reaction between the Huisgen intermediates and tryptanthrin‐malononitrile adducts in CH 2 Cl 2 under catalyst‐free conditions at room temperature (25°C), in 75% to 91% yields. The pyridopyridine or pyridoquinoline skeletons are fascinating structural motifs, which attracted the attention of synthetic chemists in recent years …”

Pyridinium Ylide-Mediated Diastereoselective Synthesis of Spirocyclopropanyl-pyrazolones via Cascade Michael/Substitution Reaction

“…(Figure ). − Over the past few years, spirocyclic pyrazole compounds have received considerable interest due to their unique structural features and extensive reaction possibilities. , Several synthetic methods for constructing spiropyrazolones have been developed, including the Diels–Alder reaction, 1,3-dipolar cycloaddition reaction, spirocyclopropanation, etc. − Recently, in 2021, Su et al reported the synthesis of spirocyclic pyrazole consisting of a cyclopropane ring system using sulfide catalysis …”

“…Based on the existing literature − and our previous research, , we hypothesized that arylidene/alkylidine-pyrazolones might serve as interesting C2/C4 synthons. These compounds could undergo Michael addition with the C1 synthon ammonium ylide followed by intramolecular substitution, resulting in the formation of spirocyclic or bicyclic privileged scaffolds (Figure ).…”