Controllable Fluorocarbon Chain Elongation: TMSCF₂Br-Enabled Trifluorovinylation and Pentafluorocyclopropylation of Aldehydes

Controllable fluorocarbon chain elongation (CFCE) is a promising yet underdeveloped strategy for the well-defined synthesis of structurally novel polyfluorinated compounds. Herein, the direct and efficient trifluorovinylation and pentafluorocyclopropylation of aldehydes are described by using TMSCF2Br (TMS = trimethylsilyl) as the sole fluorocarbon source, accomplishing the goals of CFCE from C1 to C2 and from C1 to C3, respectively. The key to the success of these CFCE processes lies in the unique and diversified chemical reactivity of TMSCF2Br, which can serve as two different precursors, namely, a TMSCF2 radical precursor and a difluorocarbene precursor. Various functional groups are amenable to this new synthetic protocol, providing streamlined access to a broad range of alcohols containing trifluorovinyl or pentafluorocyclopropyl moieties from abundantly available aldehydes. The potential utility of these methods is further demonstrated by the gram-scale synthesis, derivatization, and measurement of log P values of the products

Divergent Generation of the Difluoroalkyl Radical and Difluorocarbene via Selective Cleavage of C–S Bonds of the Sulfox-CF₂SO₂Ph Reagent

A new difluoroalkylation reagent Sulfox-CF2SO2Ph bearing both sulfoximine and sulfone moieties was prepared from commercially available SulfoxFluor and PhSO2CF2H. On one hand, the Sulfox-CF2SO2Ph reagent could act as a (phenylsulfonyl)difluoromethyl radical source under photoredox catalysis, in which the arylsulfoximidoyl group is selectively removed. On the other hand, under basic conditions, Sulfox-CF2SO2Ph could serve as a difluorocarbene precursor for S- and O-difluoromethylations with S- and O-nucleophiles, respectively, in which the phenylsulfonyl group in Sulfox-CF2SO2Ph is selectively removed (followed by α-elimination of the arylsulfoximidoyl group)

The MS and MS/MS parameters of the standards and their quantitative results.

<p>The MS and MS/MS parameters of the standards and their quantitative results.</p

MS (a) and MS/MS (b) information of 14-HDOHE.

<p>MS (a) and MS/MS (b) information of 14-HDOHE.</p

OPLS score plot of the SLE model group, PA-treated group, JP-treated group and control group by SIMCA-P11.0 (n = 10 in each group).

<p>OPLS score plot of the SLE model group, PA-treated group, JP-treated group and control group by SIMCA-P11.0 (n = 10 in each group).</p

Identification and trends of change for differential metabolites.

a<p>Change trend compared with control group.</p>b<p>Change trend compared with SLE model group.</p><p>The levels of differential metabolites were marked with (↓) down-regulated, (↑) up-regulated and (—) no significant change (*<i>P</i><0.05; **<i>P</i><0.01).</p

BPC of standards (a) and JP (b).

<p>BPC of standards (a) and JP (b).</p

(a) Merged EIC of 14-HDOHE based on the SLE model group and control group.

<p>The relative content of 14-HDOHE significantly increased in SLE model mice. (b) Merged EIC of 14-HDOHE based on SLE model group, control group, JP-treated group, and PA-treated group.</p

(a) OPLS score plot of the SLE model group (▴) and control group (▪). (b) OPLS loading plot of the SLE model group and control group.

<p>The 12 metabolites far from the origin that contributed significantly to differentiating the clustering of the SLE model group from the control group were defined as differential metabolites.</p

The perturbed metabolic network associated with SLE.

<p>The differential metabolite levels of the SLE model group compared to the control group were marked with (⇑) upregulated and (⇓) downregulated. (*Differential metabolites which could be effectively regulated by JP).</p