The unique properties of the fluorine-containing compounds
and
their widespread applications raise the demand for dependable synthetic
methods on the precise introduction of fluorine-containing substituents
into organic molecules. Herein, a site-divergent fluoroallylation
of olefins that can incorporate the fluoroallyl motif into different
alkenyl C–H sites is disclosed. gem-Difluorinated
cyclopropanes are employed as fluoroallyl sources via rhodium-catalyzed
C–C bond activation. This strategy can provide two regioisomeric
fluorinated skipped dienes in good yields with excellent site-selectivity.
The resulting products can serve as useful building blocks to access
various fluorine-containing molecules and are isosteric to β,
γ-unsaturated amides, which are promising to be exploited in
medicinal chemistry. Mechanistic studies revealed that the electronic
property of rhodium catalysts is crucial for the controllable excellent
site-selectivity, providing more insights beyond the methodology on
tuning the selectivity of metal catalysts.
A two-stage isothermal amplification method, which consists of a first-stage basic recombinase polymerase amplification (RPA) and a second-stage fluorescence loop-mediated isothermal amplification (LAMP), as well as a microfluidic-chip-based portable system, were developed in this study; these enabled parallel detection of multiplex targets in real time in around one hour, with high sensitivity and specificity, without cross-contamination. The consumption of the sample and the reagent was 2.1 μL and 10.6 μL per reaction for RPA and LAMP, respectively. The lowest detection limit (LOD) was about 10 copies. The clinical amplification of about 40 nasopharyngeal swab samples, containing 17 SARS-CoV-2 (severe acute respiratory syndrome coronavirus) and 23 measles viruses (MV), were parallel tested by using the microfluidic chip. Both clinical specificity and sensitivity were 100% for MV, and the clinical specificity and sensitivity were 94.12% and 95.83% for SARS-CoV-2, respectively. This two-stage isothermal amplification method based on the microfluidic chip format offers a convenient, clinically parallel molecular diagnostic method, which can identify different nucleic acid samples simultaneously and in a timely manner, and with a low cost of the reaction reagent. It is especially suitable for resource-limited areas and point-of-care testing (POCT).
As a special class of cyclopropanes, gem-difluorinated cyclopropanes have many fascinating properties due to the gem-difluoro substitution, and thus their reactions have received much attention from the synthetic community. Recently, gem-difluorinated cyclopropanes have gradually emerged as a type of novel and unique fluorinated allylic synthon in cross-coupling reactions for the synthesis of monofluoroalkenes. Here, we briefly summarize recent advances on transition-metal catalyzed reactions of gem-difluorinated cyclopropanes.
1. Introduction
2. Palladium catalyzed reactions with linear selectivity
3. Palladium catalyzed reactions with branched selectivity
4. Other metal catalyzed reactions
5. Conclusions
gem-Difluorinated cyclopropanes have
attracted
wide research interest in organic synthesis due to their high reactivity.
Herein, we report a Lewis acid-catalyzed cross-coupling reaction of
mono- and disubstituted gem-difluorinated cyclopropanes
with nucleophiles. The formation of a fluoroallyl cation species triggered
via the Lewis acid-assisted activation of the C–F bond is
proposed in this transformation. The cation species is then trapped
by the nucleophiles, including electron-rich arenes and allylsilanes,
to deliver a series of fluoroallylic products in good yields. The
reaction provides an alternative mode for using gem-difluorinated cyclopropanes as fluoroallyl surrogates.
We report that a nickel catalyst system with a modified 1,1′‐spirobiindane‐7,7′‐diol‐phosphoramidite (SPINOL) as the chiral ligand can enable the coupling of tertiary cyclobutenols and arylboroxines in an enantioconvergent manner, providing cyclobutenes with an all‐carbon quaternary stereocenter in good yields (up to 84 % yield) with excellent enantioselectivities (up to >99 % ee). Moreover, the catalytic system can be applied in the kinetic resolution of cyclobutenols under slightly modified conditions, giving enantioenriched tertiary cyclobutenols with an s factor of up to >200. The reaction uses free hydroxyl groups as the leaving group without additional activation while the strained ring remains untouched. Preliminary mechanistic studies reveal that the inherent discrepant reactivity of the two enantiomers is the key to the controllable enantioconvergent and kinetic resolution process.
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