The application of abundant and inexpensive fluorine
feedstock
sources to synthesize fluorinated compounds is an appealing yet underexplored
strategy. Here, we report a photocatalytic radical hydrodifluoromethylation
of unactivated alkenes with an inexpensive industrial chemical, chlorodifluoromethane
(ClCF2H, Freon-22). This protocol is realized by merging
tertiary amine-ligated boryl radical-induced halogen atom transfer
(XAT) with organophotoredox catalysis under blue light irradiation.
A broad scope of readily accessible alkenes featuring a variety of
functional groups and drug and natural product moieties could be selectively
difluoromethylated with good efficiency in a metal-free manner. Combined
experimental and computational studies suggest that the key XAT process
of ClCF2H is both thermodynamically and kinetically favored
over the hydrogen atom transfer pathway owing to the formation of
a strong boron–chlorine (B–Cl) bond and the low-lying
antibonding orbital of the carbon–chlorine (C–Cl) bond.
The
work of Kita et al. on asymmetric oxidative dearomatization
of naphthol carboxylic acids to spirolactones mediated/catalyzed by
a novel, conformationally rigid μ-oxo-bridged hypervalent iodine(III)
species is a landmark discovery in enantioselective iodine(III)
catalysis [Kita, Y.; et al. Angew. Chem., Int. Ed.
2008, 47, 3787. DOI: 10.1002/anie.200800464; J. Am. Chem. Soc.
2013, 135, 4558. DOI: 10.1021/ja401074u]. We have investigated the detailed mechanism of this important
transformation using density functional theory. Calculations revealed
that proton transfer from the pendant carboxylic acid of naphthols
to the bridging oxygen atom or the ligand of iodine(III) species,
which enhances the nucleophilicity of the carboxylic oxygen and the
nucleofugality of the iodoarene, is crucial for the dearomatizing
spirolactonization. Halogen bonding between the resulting carboxylate
and the electron-deficient iodine(III) center further stabilizes the
dearomatizing spirolactonization transition states. Calculations also
revealed a long-neglected cleaved μ-oxo iodine(III) species
that is more reactive but less selective than the μ-oxo-bridged
hypervalent iodine(III) species itself for the oxidative dearomatization
of naphthols. The coexistence of two sequential dearomatizing spirolactonization
processes in the reaction system results in a lower enantioselectivity.
A new stereochemical model that is able to reproduce and rationalize
the observed apparent enantioselectivities is proposed.
The
importance of selenium (Se) in biology and health has become
increasingly clear. Hydrogen selenide (H2Se), the biologically
available and active form of Se, is suggested to be an emerging nitric
oxide (NO)-like signaling molecule. Nevertheless, the
research on H2Se chemical biology has technique difficulties
due to the lack of well-characterized and controllable H2Se donors under physiological conditions, as well as a robust assay
for direct H2Se quantification. Motivated by these needs,
here, we demonstrate that selenocyclopropenones and selenoamides are
tunable donor motifs that release H2Se upon reaction with
cysteine (Cys) at pH 7.4 and that structural modifications enable
the rate of Cys-mediated H2Se release to be tuned. We monitored
the reaction pathways for the H2Se release and confirmed
H2Se generation qualitatively using different methods.
We further developed a quantitative assay for direct H2Se trapping and quantitation in an aqueous solution, which should
also be operative for investigating future H2Se donor motifs.
In addition, we demonstrate that arylselenoamide has the capability
of Cys-mediated H2Se release in cellular environments.
Importantly, mechanistic investigations and density functional theory
(DFT) calculations illustrate the plausible pathways of Cys-activated
H2Se release from arylselenoamides in detail, which may
help understand the mechanistic issues of the H2S release
from pharmacologically important arylthioamides. We anticipate that
the well-defined chemistries of Cys-activated H2Se donor
motifs will be useful for studying Se biology and for development
of new H2Se donors and bioconjugate techniques.
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