Halogen-Induced Controllable Cyclizations as Diverse Heterocycle Synthetic Strategy

China, Hideyasu; Kumar, Ravi; Kikushima, Kotaro; Dohi, Toshifumi

doi:10.20944/preprints202012.0295.v1

“…In addition to changing chemistry, the way chemists approach this subject is also constantly evolving. Unconventional, yet valuable concepts have been introduced into the field, including but not limited to late-stage functionalization, 12 atom economy, 13,14 bifunctional reagents, 15 divergent syntheses, [16][17][18][19][20] and multicomponent reactions. 21 Indeed, these strategies allow scientists to access broader chemical space for achieving synthetic endeavors.…”

mentioning

confidence: 99%

Solvent-Controlled Switchable Synthesis of gem-Difluoro Compounds from Anhydrides under Photoredox Catalysis

Giri

¹

,

Mosiagin

²

,

Franzoni³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

The outstanding impact of fluorine atom in drug discovery cannot be overestimated. Substantially, the incorporation of the gem-difluoro (CF2) group into organic frameworks is highly sought due to the influence of this unit on physicochemical and pharmacological properties of molecules. Yet, introduction of CF2 moiety into organic structures is a step-intensive preparation, and known approaches are often limited to certain classes of molecules. Development of strategies for a rapid incorporation of gem-difluoro synthon that utilizes inexpensive commercial reagents is highly desirable. In the context of divergency and applicability of such reagents, switchable synthesis can be beneficial to access a wide range of fluorinated compounds. Herein we report a mild and operationally simple protocols to access various gem-difluoro compounds that employs chlorodifloroacetic anhydride (CDFAA) as a low cost and versatile fluoroalkylating reagent. Detailed mechanistic investigations revealed that electron-transfer photocatalysis triggers mesolytic cleavage of a C−Cl bond generating a gem-difluoro carboxy radical. In the presence of alkene molecule, this radical species acts as an efficient and unique bifunctional reagent that, under solvent-controlled reaction conditions, delivers a wide range of gem-difluorinated γ-lactams, γ-lactones, as well as promotes oxy-perfluoroalkylation. These protocols are flow and batch scalable, possess excellent chemo- and regioselectivity, and can be used for the late-stage diversification of biorelevant molecules.

show abstract

“…In addition to changing chemistry, the way chemists approach this subject is also constantly evolving. Unconventional, yet valuable concepts have been introduced into the field, including but not limited to late-stage functionalization, 12 atom economy, 13,14 bifunctional reagents, 15 divergent syntheses, [16][17][18][19][20] and multicomponent reactions. 21 Indeed, these strategies allow scientists to access broader chemical space for achieving synthetic endeavors.…”

mentioning

confidence: 99%

Solvent-Controlled Switchable Synthesis of gem-Difluoro Compounds from Anhydrides under Photoredox Catalysis

Giri

¹

,

Mosiagin

²

,

Franzoni³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

The outstanding impact of fluorine atom in drug discovery cannot be overestimated. Substantially, the incorporation of the gem-difluoro (CF2) group into organic frameworks is highly sought due to the influence of this unit on physicochemical and pharmacological properties of molecules. Yet, introduction of CF2 moiety into organic structures is a step-intensive preparation, and known approaches are often limited to certain classes of molecules. Development of strategies for a rapid incorporation of gem-difluoro synthon that utilizes inexpensive commercial reagents is highly desirable. In the context of divergency and applicability of such reagents, switchable synthesis can be beneficial to access a wide range of fluorinated compounds. Herein we report a mild and operationally simple protocols to access various gem-difluoro compounds that employs chlorodifloroacetic anhydride (CDFAA) as a low cost and versatile fluoroalkylating reagent. Detailed mechanistic investigations revealed that electron-transfer photocatalysis triggers mesolytic cleavage of a C−Cl bond generating a gem-difluoro carboxy radical. In the presence of alkene molecule, this radical species acts as an efficient and unique bifunctional reagent that, under solvent-controlled reaction conditions, delivers a wide range of gem-difluorinated γ-lactams, γ-lactones, as well as promotes oxy-perfluoroalkylation. These protocols are flow and batch scalable, possess excellent chemo- and regioselectivity, and can be used for the late-stage diversification of biorelevant molecules.

show abstract

Recent Progress in Heterocycle Synthesis: Cyclization Reaction with Pyridinium and Quinolinium 1,4-Zwitterions

Wang

¹

,

Zhao

²

,

Zhang

³

et al. 2023

View full text Add to dashboard Cite

Heteroarene 1, n-zwitterions are powerful and versatile building blocks in the construction of heterocycles and have received increasing attention in recent years. In particular, pyridinium and quinolinium 1,4-zwitterions have been widely studied and used in a variety of cyclization reactions due to their air stability, ease of use, and high efficiency. Sulfur- and nitrogen-based pyridinium and quinolinium 1,4-zwitterions, types of emerging heteroatom-containing synthons, have attracted much attention from chemists. These 1,4-zwitterions, which contain multiple reaction sites, have been successfully used in the synthesis of three- to eight-membered cyclic compounds over the last decade. In this review, we present the exciting progress made in the field of cyclization reactions of sulfur- and nitrogen-based pyridinium and quinolinium 1,4-zwitterions. Moreover, the mechanistic insights, the transition states, some synthetic applications, and the challenges and opportunities are also discussed. We hope to provide an overview for synthetic chemists who are interested in the heterocycle synthesis from cyclization reaction with pyridinium and quinolinium 1,4-zwitterions pyridinium and quinolinium 1,4-zwitterions.

show abstract

Halogen-Induced Controllable Cyclizations as Diverse Heterocycle Synthetic Strategy

Cited by 5 publications

References 97 publications

Solvent-Controlled Switchable Synthesis of gem-Difluoro Compounds from Anhydrides under Photoredox Catalysis

Solvent-Controlled Switchable Synthesis of gem-Difluoro Compounds from Anhydrides under Photoredox Catalysis

Solvent-Controlled Switchable Synthesis of gem-Difluoro Compounds from Anhydrides under Photoredox Catalysis

Recent Progress in Heterocycle Synthesis: Cyclization Reaction with Pyridinium and Quinolinium 1,4-Zwitterions

Contact Info

Product

Resources

About