Catalytic Diversification of gem‐Difluorocyclopropanes: Recent Advances and Challenges

Abstract

gem‐Difluorocyclopropanes (F2CPs) have aroused considerable attention not only from the structural perspective but also due to their ability to participate in various valuable transformations. This Review summarizes advances in catalytic ring‐opening reactions of gem‐F2CPs, especially emphasizing the reactivities and applications of those non‐activated ones under transition‐metal catalysis. Their achievements, synthetic applications and limitations are discussed with the aim to stimulate enthusiasm for further development.

Lewis Acid-Catalyzed Ring-Opening Cross-Coupling Reaction of gem-Difluorinated Cyclopropanes Enabled by C–F Bond Activation

“…In this context, gem -difluorinated cyclopropanes, which are readily accessible via the gem -difluorocyclopropanation of olefins, have emerged as versatile fluorine-containing building blocks in organic synthesis. The dominant reaction mode of gem -difluorinated cyclopropanes involves C–C bond activation followed by β-fluoride elimination via transition-metal catalysis, where the fluoroallyl metal species is the key intermediate that can couple with a wide range of nucleophiles to deliver linear or branched fluoroallyl products (Scheme a). − In these reactions, the ring-opening transformation is initiated with C–C bond activation via oxidative addition. In addition, there have been sporadic reports on the reaction of gem -difluorinated cyclopropanes involving a radical mechanism or organocatalysis. , …”

Facile access to gem-difluorocyclopropanes via an N-heterocyclic carbene-catalyzed radical relay/cyclization strategy

“…gem-Difluorocyclopropanes, bearing two fluorine atoms at the same carbon atom at the strained three-membered ring, have been proven to be attractive and useful building blocks in organic synthesis because of their ability to participate in various ring-opening reactions. [1][2][3][4][5][6] Additionally, considering the indispensable role of fluorinated compounds in medicinal chemistry and agrochemistry, gem-difluorocyclopropanes have also been incorporated into biologically active compounds as emerging fluorinated motifs (Scheme 1a). 2,7,8 Therefore, the synthetic approaches of gem-difluorocyclopropanes have also drawn much attention in recent years.…”

Synthesis of α-Difluoromethylene Ethers via Photoredox-Induced Hyperconjugative Ring Opening of gem-Difluorocyclopropanes

“…In this regard, Feng and co-workers have developed a series of photoredox-catalyzed carbon–carbon (C–C) bond cleavage-functionalization of cyclopropanes . Although the transition-metal-catalyzed ring opening of gem -difluorocyclopropane generally afforded defluorinated products − (Scheme c), the photoredox-induced C–C bond cleavage of gem -difluorocyclopropane in the presence of Et 3 N·3HF furnished trifluoromethylated products (Scheme d). Herein, we report a visible light-promoted C–C bond cleavage of gem -difluorocyclopropanes to construct α-difluoromethylene ether architectures (Scheme e).…”