Synthesis of gem ‐Difluorocyclopropanes

Difluorocarbene Generation from TMSCF3: Kinetics and Mechanism of NaI-Mediated and Si-Induced Anionic Chain Reactions

“…In contrast, co-reactions of TESCF3 ( 19) and TMSCF3 (1) mediated by NaI, proceeded selectively (kTMS / kTES ~ 30, see S3.9BC in the SI) in both the presence and absence of alkene 3i. This is consistent with siliconates (2,20) being disfavored in the presence of Na + , allowing the selective reaction of the more fluorophilic reagent 1.…”

“…The unique properties of cyclopropanes leads to useful effects on their fluorination, 1 with the application of difluorocyclopropanes being especially prominent. [1][2] The latter are most commonly prepared by alkene-difluorocyclopropanation, [1][2][3] nominally via in situ capture of singlet CF2, 4 and over the last 50 years, a very broad range of reagents have been developed for this process. [5][6][7][8][9][10] However, many of these reagents have limitations, inter alia, toxicity, the use of strong bases, or the need for high-temperatures.…”

Pd-catalyzed access to mono- and di-fluoroallylic amines from primary anilines

“…However, the synthesis of their fluorinated equivalents is starkly underdeveloped, and constitutes a major challenge. In this context, gem -difluorocyclopropanes 23–25 are composed of a fluorine-containing strained three-membered ring structure, and are easily accessible (see the ESI†). Moreover, these motifs can be readily activated at the C–C and C–F bonds under transition metal catalysis, such as with Pd, 26–36 Rh, 37 or other metals, usually leading to the corresponding fluorinated allylic metal complexes.…”

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.…”

“…2,7,8 Therefore, the synthetic approaches of gem-difluorocyclopropanes have also drawn much attention in recent years. Generally, there are four pathways to obtain gem-difluorocyclopropane motifs (Scheme 1b), 1,9 among them the direct difluorocyclopropanation of alkenes with difluorocarbenes derived from various related precursors has been established as the most reliable protocol (Scheme 1b, iv). Nevertheless, some of these methods suffer from limitations such as high reaction temperature, lack of commercial availability of the starting materials, limited substrate scope and so on.…”