In the last few years, the development of versatile methodologies to incorporate trifluoromethyl groups into organic molecules has attracted significant attention in synthetic chemistry. This review ...gives an overview over the development on the trifluoromethylation of alkynes, which have not been solely discussed before. Formation of diverse C(sp, sp2, sp3)CF3 bonds are all covered in this review.
Versatile methodologies for the incorporation of trifluoromethyl groups into organic molecules have attracted significant attention in synthetic chemistry. This Minireview highlights the recent efforts on the development of trifluoromethylation of alkynes to construct various diverse C(sp, sp2, sp3)CF3 bonds by radical processes, or through transition‐metal catalysis by using nucleophilic or electrophilic trifluoromethylation reagents (see scheme).
The cross‐electrophile coupling has become a powerful tool for C−C bond formation, but its potential for forging the C−Si bond remains unexplored. Here we report a cross‐electrophile Csp2‐Si coupling ...reaction of vinyl/aryl electrophiles with vinyl chlorosilanes. This new protocol offers an approach for facile and precise synthesis of organosilanes with high molecular diversity and complexity from readily available materials. The reaction proceeds under mild and non‐basic conditions, demonstrating a high step economy, broad substrate scope, wide functionality tolerance, and easy scalability. The synthetic utility of the method is shown by its efficient accessing of silicon bioisosteres, the design of new BCB‐monomers, and studies on the Hiyama cross‐coupling of vinylsilane products.
Organosilanes: A new C−Si bond‐forming reaction via C−X and Si−Cl cleavage was achieved by reductive nickel catalysis. This method bridges the gap between the cross‐electrophile coupling and organosilicon chemistry. It offers very mild reaction conditions for facile and precise synthesis of structurally versatile vinylsilanes that have found applications in many fields.
We report here a new method for the synthesis of organohydrosilanes from phenols and ketones. This method is established through reductive C−Si coupling of chlorohydrosilanes via unconventional Si−Cl ...cleavage. The reaction offers access to aryl‐ and alkenylhydrosilanes with a scope that is complementary to those of the established methods. Electron‐rich, electron‐poor, and ortho‐/meta‐/para‐substituted (hetero)aryl electrophiles, as well as cyclic and acyclic alkenyl electrophiles, were coupled successfully. Functionalities, including Grignard‐sensitive groups (e.g., primary amine, amide, phenol, ketone, ester, and free indole), acid‐sensitive groups (e.g., ketal and THP protection), alkyl‐Cl, pyridine, furan, thiophene, Ar‐Bpin, and Ar‐SiMe3, were tolerated. Gram‐scale reaction, incorporation of ‐Si(H)R2 into complex biologically active molecules, and derivatization of formed organohydrosilanes are demonstrated.
A new C−Si bond‐forming reaction between R−X and Cl−Si(H)R2 was achieved using reductive nickel catalysis. This method offers access to structurally diverse aryl‐ and alkenylhydrosilanes from phenol and ketone derivatives. The reaction can be conducted on gram scale and allows for incorporating a hydrosilane moiety into biologically active molecules.
Catalytic transformation of alcohols via metal-catalyzed cross-coupling reactions is very important, but it typically relies on a multistep procedure. We here report a dynamic kinetic cross-coupling ...approach for the direct functionalization of alcohols. The feasibility of this strategy is demonstrated by a nickel-catalyzed cross-electrophile arylation reaction of benzyl alcohols with (hetero)aryl electrophiles. The reaction proceeds with a broad substrate scope of both coupling partners. The electron-rich, electron-poor, and ortho-/meta-/para-substituted (hetero)aryl electrophiles (e.g., Ar-OTf, Ar-I, Ar-Br, and inert Ar-Cl) all coupled well. Most of the functionalities, including aldehyde, ketone, amide, ester, nitrile, sulfone, furan, thiophene, benzothiophene, pyridine, quinolone, Ar-SiMe
, Ar-Bpin, and Ar-SnBu
, were tolerated. The dynamic nature of this method enables the direct arylation of benzylic alcohol in the presence of various nucleophilic groups, including nonactivated primary/secondary/tertiary alcohols, phenols, and free indoles. It thus offers a robust alternative to existing methods for the precise construction of diarylmethanes. The synthetic utility of the method was demonstrated by a concise synthesis of biologically active molecules and by its application to peptide modification and conjugation. Preliminary mechanistic studies revealed that the reaction of in situ formed benzyl oxalates with nickel, possibly via a radical process, is an initial step in the reaction with aryl electrophiles.
Catalytic alkylation of stable alkenyl C−O electrophiles is synthetically appealing, but studies to date have typically focused on the reactions with alkyl Grignard reagents. We report herein a ...cross‐electrophile reaction of alkenyl acetates with alkyl bromides. This work has enabled a new method for the synthesis of aliphatic alkenes from alkenyl acetates to be established that can be used to add more structural complexity and molecular diversity with enhanced functionality tolerance. The method allows for a gram‐scale reaction and modification of biologically active molecules, and it affords access to useful building blocks. Preliminary mechanistic studies reveal that the NiI species plays an essential role for the success of the coupling of these two reactivity‐mismatched electrophiles.
A new C−C bond‐forming reaction between alkenyl acetates and alkyl bromides was achieved by reductive nickel catalysis. This method offers very mild reaction conditions for facile and precise synthesis of structurally versatile aliphatic alkenes using readily available and stable alkenyl reagents. It allows for a gram‐scale reaction and modification of biologically active molecules, and it affords access to useful building blocks.
The cross-electrophile reaction is a promising strategy for C–C bond formation. Recent studies have focused mainly on reactions with organic halides. Here we report a coupling reaction between C–N ...and C–O electrophiles that demonstrates the possibility of constructing a C–C bond via C–N and C–O cleavage. Several reactions between benzyl/aryl ammonium salts and vinyl/aryl C–O electrophiles have been studied. Preliminary mechanistic studies revealed that the benzyl ammoniums were activated through a radical mechanism.
A copper‐catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent sodium trifluoromethanesulfinate (NaSO2CF3 or Langlois’ reagent) has been developed incorporating ...a tandem cyclization/dearomatization process. This strategy affords a straightforward route to synthesis of 3‐(trifluoromethyl)‐spiro4.5trienones, and presents an example of difunctionalization of alkynes for simultaneous formation of two carbon–carbon single bonds and one carbon–oxygen double bond.
Spiro mania: A copper‐catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent NaSO2CF3 has been reported, affording a series of 3‐trifluoromethyl spiro4.5trienones through a tandem cyclization/dearomatization process. In this alkyne difunctionalization process, two carbon–carbon bonds and one carbon–oxygen double bond are simultaneously formed.
C‐aryl glycosides are popular basic skeletons in biochemistry and pharmaceutical chemistry. Herein, ruthenium‐catalyzed highly stereo‐ and site‐selective ortho‐ and meta‐CAr−H glycosylation is ...described. A series of C‐aryl pyranosides and furanosides were synthesized by this method. The strategy showed good substrate scope, and various N‐heterocyclic directing groups were compatible with the reaction system. A mechanistic study suggested that the key pathway of ortho‐CAr−H glycosylation might involve oxidative addition/reduction elimination, whereas aryl meta‐C−H glycosylation was mediated by σ‐activation. Density functional theory calculations also showed that the high stereoselectivity of meta‐CAr−H glycosylation was due to steric hindrance.
A series of C‐aryl pyranosides and furanosides were synthesized by ruthenium‐catalyzed ortho‐ and meta‐CAr−H glycosylation. Mechanistic studies suggest that the key pathway of ortho‐CAr−H glycosylation involves an oxidative addition/reductive elimination process, while aryl meta‐C−H glycosylation is mediated by σ‐activation. DFT calculations showed that steric hindrance is responsible for the high stereoselectivity of meta‐CAr−H glycosylation.
Long noncoding RNAs (lncRNAs) are emerging as important regulators of multiple cellular processes such as cell invasion, growth, apoptosis and differentiation. LncRNAs can function as competing ...endogenous RNAs (ceRNAs) which sponge and sequester microRNA (miRNA) to regulate specific targets. Previously, we found that the target genes of several miRNAs, including FADD, Fas, Casp and Bax, are related to neuronal apoptosis and form a regulatory network. Among several factors, microRNA‐296‐5p expression was found to be negatively correlated with caspase activity and apoptosis. Here, we aimed to investigate the role of miR‐296‐5p in neuroblastoma (NB) cells. By performing quantitative real‐time PCR (qRT‐PCR), western blot and flow cytometry assays we analysed the expression of apoptotic markers in NB cells transfected with miR‐296‐5p mimics or inhibitor. Pathway‐specific PCR array allowed us to identify the target genes of miR‐296‐5p. Using LncBase online tool, we predicted lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) as an upstream regulator of miR‐296‐5p. The binding of KCNQ1OT1 and miR‐296‐5p was validated via RNA immunoprecipitation and Biotin pull‐down assays. We also demonstrate that miR‐296‐5p suppresses apoptosis of NB cells in vitro and in vivo. Mechanistically, miR‐296‐5p directly bound the 3′UTR of Bax mRNA, thus repressing Bax at the mRNA and protein level. Moreover, through bioinformatic analysis and molecular experiments, we showed that KCNQ1OT1 sponged miR‐296‐5p and impaired its effect on NB cell apoptosis. In summary, KCNQ1OT1 is a potent promoting factor of cell apoptosis, which acts by sponging miR‐296‐5p and upregulating Bax. Our findings identify a regulatory axis of cell fate in NB cells.
Increasing evidence shows that long noncoding RNAs (lncRNAs) can function as competing endogenous RNAs by sponging microRNAs in a sequence‐specific manner and impairing their functions of binding and suppressing target mRNAs. Through bioinformatic analysis and subsequent molecular experiments, we implied that lncRNA KCNQ1 opposite strand/antisense transcript 1 promotes Bax expression and neuroblastoma cells apoptosis by direct binding with miR‐296‐5p.
Transition‐metal catalyzed difunctionalization of olefins has attracted considerable attention as a method to construct carbon‐carbon and carbon‐hetero bonds. Herein, the copper‐catalyzed ...three‐component radical cross‐coupling of oxime esters, styrenes and AgSCF3 through a visible‐light‐promoted iminyl radical‐mediated carbon‐carbon bond cleavage strategy has been described. Utilizing low‐cost copper salt as both photosensitizers and cross‐couplers, this protocol delivers diverse target products, providing a supplementary approach for cyanoalkylation and trifluoromethylthiolation of drug molecules.
