Selective introduction of fluorine into molecules by the cleavage of inert C−H bonds is of central academic and synthetic interest, yet remains challenging. Given the central role of alcohols in ...organic chemistry as the most ubiquitous building blocks, a versatile and selective C(sp3)−H and C(sp2)−H fluorination of simple alcohols, enabled by novel designed exo‐directing groups, is described. C(sp2)−H bond fluorination was achieved by using a simple acetone oxime as auxiliary, whereas a new, modular and easily accessible bidentate auxiliary was developed for the efficient and site‐selective fluorination of various primary methyl, methylene, and benzylic C(sp3)−H bonds. Fluorinated alcohols can readily be accessed by the removal of auxiliaries, and significantly expands the synthetic prospect of the present procedure.
A versatile and selective C(sp3)−H and C(sp2)−H fluorination of simple alcohols, enabled by an exo‐directing group (DG) is described. C(sp2)−H bond fluorination was achieved by using simple acetone oxime as an auxiliary, whereas a new and modularly accessible bidentate auxiliary was developed for the efficient and site‐selective fluorination of C(sp3)−H bonds. The auxiliary is removable and demonstrates broad substrate scope and excellent selectivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A novel palladium catalyzed highly para-selective C-H difluoromethylation of electron-deficient aromatic carbonyls was developed. Diverse substituted aromatic ketones and benzoates were selectively ...difluoromethylated at the remote para-site of carbonyl groups in moderate to good yields. Moreover, the difuoromethylation was also compatible with several complex bioactive molecules.
Background
This study was designed to verify whether enhancer of zeste homolog 2 (EZH2) affects intervertebral disc degeneration (IVDD) development through regulation of microRNA (miR)‐129‐5p/MAPK1.
...Methods
Initially, we collected lumbar nucleus pulposus (NP) tissue samples from patients with juvenile idiopathic scoliosis (n = 14) and IVDD (n = 34). We measured the expression of related genes in clinical IVDD tissues and a lipopolysaccharide (LPS)‐induced NP cell model. After loss‐ and gain‐of‐function assays, NP cell proliferation and senescence were examined. The targeting relationship between miR‐129‐5p and MAPK1 was explored by dual luciferase reporter gene and RNA immunoprecipitation (RIP) assays. The enrichment of EZH2 and H3K27me3 in miR‐129‐5p promoter was verified by chromatin immunoprecipitation (ChIP). Finally, an IVDD rat model was established to test the effects of transduction with lentiviral vector carrying miR‐129‐5p agomir and/or oe‐EZH2 in vivo.
Results
miR‐129‐5p was underexpressed, and EZH2 and MAPK1 levels were overexpressed in lumbar nucleus pulposus from human IVDD patients and in LPS‐induced NP cells. miR‐129‐5p overexpression or silencing of MAPK1 promoted proliferation of NP cells, while inhibiting their senescence. EZH2 inhibited miR‐129‐5p through H3K27me3 modification in the miR‐129‐5p promoter. miR‐129‐5p could target the downregulation of MAPK1 expression. EZH2 overexpression increased the release of inflammatory factors and cell senescence factors, which was reversed by miR‐129‐5p agomir in vivo.
Conclusions
Taken together, EZH2 inhibits miR‐129‐5p through H3K27me3 modification, which upregulates MAPK1, thereby promoting the development of IVDD.
EZH2 can inhibit the transcription of miR‐129‐5p through epigenetic regulation of H3K27me3 modification in the miR‐129‐5p promoter, which upregulates the expression of MAPK1, inhibits the proliferation of NP cells, and promotes their senescence to promote IVDD development.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A versatile and site-selective nitrate-promoted C–H bond fluorination using various weak coordinating amides as intrinsic directing groups was developed. Diverse tertiary and secondary amides ...underwent selective aromatic C–H bond fluorination, which features broad substrate scope, good regioselectivity, and mild conditions. Moreover, the late-stage C–H bond fluorination of the challenging benzeneacetamides via distal directing was reported for the first time.
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IJS, KILJ, NUK, PNG, UL, UM
The synthesis of stereo-defined α-trifluoromethyl arylenes is of great importance in medical chemistry, organic chemistry, and materials science. However, despite the recent advances, the Z-selective ...formation of α-trifluoromethyl arylenes has remained underdeveloped. Here, we describe a facile approach towards Z-α-trifluoromethyl arylenes through Pd-catalysed stereoselective fluoroarylation of 1,1-difluoroallenes in the presence of a bulky monophosphine ligand.
The Pd-cataylsed direct
ortho
-C(sp
2
)-H fluorination of aromatic ketones has been developed for the first time. The reaction features good regioselectivity and simple operations, constituting an ...alternative shortcut to access fluorinated ketones. A concise synthesis of anacetrapib has also been achieved by using late-stage C-H fluorination as a key step.
The direct aromatic C-H bond fluorination of ketones was developed for the first time, providing a short alternative to access anacetrapib through late-stage C-H bond fluorination.
An efficient Pd-catalysed β-C(sp
3
)-H arylation of diverse native amides with aryl iodides was developed. This protocol overcomes the necessity of the Thorpe-Ingold effect and features broad ...substrate scope and good functional group tolerance. The potential application of this protocol is collectively demonstrated by gram-scale synthesis and the synthesis of several bioactive molecules.
A practical and concise approach for the synthesis of β-aryl amides and γ-aryl amines has been developed by utilizing the innate carbonyl of native amides as valid coordinating groups.
A detailed mechanism study on the anion ligand promoted selective C-H bond fluorination is reported. The role of the anion ligand has been clarified by experimental evidence and DFT calculations. ...Moreover, the nitrate promoted C-F bond reductive elimination enabled a selective C-H bond fluorination of various symmetric and asymmetric azobenzenes to access diverse
o
-fluoroanilines.
A detailed mechanism study on the anion ligand promoted selective C-H bond fluorination is reported.
Herein, we report a novel strategy to access CH
2
F-containing ketones through Pd-catalysed β-selective methyl C(sp
3
)-H fluorination. The reaction features high regioselectivity and a broad ...substrate scope, constituting a modular method for the late-stage transformation of the native methyl (CH
3
) into the monofluoromethyl (CH
2
F) group.
A novel strategy was developed for the modular synthesis of CH
2
F-containing ketones through palladium catalysed β-selective methyl C(sp
3
)-H fluorination.
A palladium catalyzed selective C(sp
3
)-H arylation and acetoxylation of alcohols using a practical bidentate auxiliary were developed. Masked alcohols were selectively arylated at the β-position ...with diverse aryl iodides for the first time. Moreover, an efficient and site-selective acetoxylation of various primary methyl, methylene, and benzylic C(sp
3
)-H bonds was performed by using cheap K
2
S
2
O
8
as the external oxidant.
A palladium catalyzed selective C(sp
3
)-H arylation and acetoxylation of alcohols using a practical bidentate auxiliary were developed.
