Development of pentafluoroethylation methods.

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Fluorine Chemistry

Background:

• The trifluoromethyl (CF3) group is well-established, while the pentafluoroethyl (C2F5) group has been less explored synthetically and in applications.
• A growing body of literature now details efficient methods for synthesizing C2F5-containing compounds.
• This shift highlights the increasing recognition of the C2F5 group's potential.

Purpose of the Study:

• To comprehensively review synthetic methods for pentafluoroethylation published between approximately 2015 and 2025.
• To categorize these methods based on the types of reagents employed.
• To underscore the advancements in accessing diverse C2F5-substituted molecules.

Main Methods:

• Review of literature focusing on pentafluoroethylation reagents and reactions.
• Categorization of methods by reagent class: transition metal-based, perfluoroalkyl silanes, gaseous reagents, hypervalent iodine, sulfonium ylides, sulfoximines, and others.
• Analysis of the period from circa 2015 to 2025.

Main Results:

• Significant progress has been made in developing efficient pentafluoroethylation strategies.
• A wide array of reagents now facilitates the introduction of the C2F5 group.
• Structurally diverse pentafluoroethylated compounds are now more accessible.

Conclusions:

• Recent synthetic advancements have greatly improved access to pentafluoroethylated compounds.
• These compounds hold significant promise for applications in medicinal chemistry as drug candidates.
• They also serve as valuable building blocks in organic synthesis.