- Solid-state construction of zigzag periphery: Via intramolecular C-H insertion induced by alumina-mediated C-F activation
-
Caryl-F bond activation has become an important and quickly developing method for construction of carbon-based materials. We report that alumina-mediated C-F bond activation (AmCFA) enables construction of PAHs with zigzag periphery. This method includes
- Akhmetov, Vladimir,Amsharov, Konstantin,F?rtsch, Andreas,Feofanov, Mikhail
-
p. 12325 - 12328
(2021/11/30)
-
- Further lead optimization on Bax activators: Design, synthesis and pharmacological evaluation of 2-fluoro-fluorene derivatives for the treatment of breast cancer
-
To further pursue potent Bax activators with better safety profiles for the treatment of breast cancer, structural optimization was conducted based on lead compound CYD-4-61 through several strategies, including scaffold hopping on the 2-nitro-fluorene ring, replacement of the nitro group with bioisosteres to avoid potential toxicity, and further optimization on the upper pyridine by exploring diverse alkylamine linkers as a tail or replacing the pyridine with bioisosteric heterocycles. F-containing compound 22d (GL0388) exhibited a good balance between the activity and toxicity, displaying submicromolar activities against a variety of cancer cell lines with 5.8–10.7-fold selectivity of decreased activity to MCF-10A human mammary epithelial cell line. Compound 22d dose-dependently blocked colony formation of breast cancer cells and prevented the migration and invasion of MDA-MB-231 cells. Mechanism of action studies indicate that 22d activated Bax, rendering its insertion into mitochondrial membrane, thereby leading to cytochrome c release from the mitochondria into the cytoplasm, subsequently inducing release of apoptotic biomarkers. Further in vivo efficacy studies of 22d in human breast cancer xenografts arisen from MDA-MB-231 cells demonstrated that this drug candidate significantly suppressed tumor growth, indicating the therapeutic promise of this class of compounds for the treatment of breast cancer as well as the potential for developing F-radiolabeled imaging ligands as anticancer chemical probes.
- Liu, Gang,Kim, Hyejin,Wang, Pingyuan,Fricke, Doerte R.,Chen, Haiying,Wang, Tianzhi,Shen, Qiang,Zhou, Jia
-
-
- A comprehensive study of substituent effects on poly(dibenzofulvene)s
-
We herein report the first cross comparison of 14 poly(dibenzofulvene) derivatives (13 novel examples and the parent poly(dibenzofulvene)) in order to understand how the choice of substituent affects the physical properties of this interesting class of semiconducting polymers. Electron withdrawing substituents decreased the polymerization reactivity and resulted in very low molecular-weight products. Di-substituted poly(dibenzofulvene)s were found to be much less soluble than the mono-analogues which can be explained by the Hansen solubility parameter system. Analysis based on absorption, emission and electrochemistry profiles suggests that polymer solubility is a very important factor that controls the degree of stacking present in the polymer due to synthetic issues. For the first time, the thermal analysis of the parent poly(dibenzofulvene) and its derivatives is reported and it was believed that depolymerization occurred much earlier than the melting transition. We have also demonstrated the orthogonal synthesis of dibenzofulvene monomers using three distinct routes (lithiation, oxidation and Wittig) to cope with functional group compatibility.
- Wong, Michael Y.,Leung, Louis M.
-
p. 512 - 520
(2017/02/05)
-
- Palladium-Catalyzed Formal [4 + 1] Annulation via Metal Carbene Migratory Insertion and C(sp2)-H Bond Functionalization
-
A highly efficient and operationally simple palladium-catalyzed formal [4 + 1] annulation reaction has been developed. The reaction is featured by the formation of two different C-C bonds on a carbenic center. It represents a concise method for the synthesis of a wide range of polycyclic aromatic hydrocarbons (PAHs) and 1H-indenes with easily available (trimethylsilyl)diazomethane as the carbene source. Metal carbene migratory insertion and C(sp2)-H bond activation are proposed as the key steps in this transformation. The reaction further demonstrates the versatility of the carbene-based coupling in combination with various transition-metal-catalyzed transformations.
- Xu, Shuai,Chen, Ri,Fu, Zihao,Zhou, Qi,Zhang, Yan,Wang, Jianbo
-
p. 1993 - 1997
(2017/08/14)
-
- Au-catalyzed biaryl coupling to generate 5- to 9-membered rings: Turnover-limiting reductive elimination versus π-complexation
-
The intramolecular gold-catalyzed arylation of arenes by aryl-trimethylsilanes has been investigated from both mechanistic and preparative aspects. The reaction generates 5- to 9-membered rings, and of the 44 examples studied, 10 include a heteroatom (N, O). Tethering of the arene to the arylsilane provides not only a tool to probe the impact of the conformational flexibility of Ar-Au-Ar intermediates, via systematic modulation of the length of aryl-aryl linkage, but also the ability to arylate neutral and electron-poor arenes-substrates that do not react at all in the intermolecular process. Rendering the arylation intramolecular also results in phenomenologically simpler reaction kinetics, and overall these features have facilitated a detailed study of linear free energy relationships, kinetic isotope effects, and the first quantitative experimental data on the effects of aryl electron demand and conformational freedom on the rate of reductive elimination from diaryl-gold(III) species. The turnover-limiting step for the formation of a series of fluorene derivatives is sensitive to the reactivity of the arene and changes from reductive elimination to π-complexation for arenes bearing strongly electron-withdrawing substituents (σ > 0.43). Reductive elimination is accelerated by electron-donating substituents (ρ = -2.0) on one or both rings, with the individual σ-values being additive in nature. Longer and more flexible tethers between the two aryl rings result in faster reductive elimination from Ar-Au(X)-Ar and lead to the π-complexation of the arene by Ar-AuX2 becoming the turnover-limiting step.
- Corrie, Tom J. A.,Ball, Liam T.,Russell, Christopher A.,Lloyd-Jones, Guy C.
-
supporting information
p. 245 - 254
(2017/05/29)
-
- Au-Catalyzed Biaryl Coupling to Generate 5- To 9-Membered Rings: Turnover-Limiting Reductive Elimination versus ?-Complexation
-
The intramolecular gold-catalyzed arylation of arenes by aryl-trimethylsilanes has been investigated from both mechanistic and preparative aspects. The reaction generates 5- to 9-membered rings, and of the 44 examples studied, 10 include a heteroatom (N, O). Tethering of the arene to the arylsilane provides not only a tool to probe the impact of the conformational flexibility of Ar-Au-Ar intermediates, via systematic modulation of the length of aryl-aryl linkage, but also the ability to arylate neutral and electron-poor arenes - substrates that do not react at all in the intermolecular process. Rendering the arylation intramolecular also results in phenomenologically simpler reaction kinetics, and overall these features have facilitated a detailed study of linear free energy relationships, kinetic isotope effects, and the first quantitative experimental data on the effects of aryl electron demand and conformational freedom on the rate of reductive elimination from diaryl-gold(III) species. The turnover-limiting step for the formation of a series of fluorene derivatives is sensitive to the reactivity of the arene and changes from reductive elimination to ?-complexation for arenes bearing strongly electron-withdrawing substituents (σ > 0.43). Reductive elimination is accelerated by electron-donating substituents (ρ = -2.0) on one or both rings, with the individual σ-values being additive in nature. Longer and more flexible tethers between the two aryl rings result in faster reductive elimination from Ar-Au(X)-Ar and lead to the ?-complexation of the arene by Ar-AuX2 becoming the turnover-limiting step.
- Ball, Liam T.,Corrie, Tom J. A.,Lloyd-Jones, Guy C.,Russell, Christopher A.
-
supporting information
p. 245 - 254
(2021/09/04)
-
- New electron-accepting quinoxalinothiadiazole-containing heterocycles as promising building blocks for organic optoelectronic devices
-
Two novel quinoxalinothiadiazole-containing dibromides—4,9-dibromo-6,7-bis(9,9-didodecyl7-fluoro-9H-fluoren-2-yl)[1,2,5]thiadiazolo[3,4-g]quinoxaline (11) and 4,9-dibromo-6,7-bis(9,9-didodecyl-5,7-difluoro-9H-fluoren-2-yl)[1,2,5]thiadiazolo[3,4-g]quinoxaline (19)—have been synthesized, which are promising strong electron-accepting building blocks for preparing highly efficient narrow-bandgap D–A conjugated polymers. The composition and structure of monomers 11 and 19 have been proved by elemental analysis data, IR spectroscopy, and 1H and 13C NMR.
- Keshtov,Konstantinov,Krayushkin,Kuklin,Masoud,Osipov,Khokhlov
-
p. 202 - 207
(2016/07/21)
-
- Synthesis of new D-A1-D-A2 type low bandgap terpolymers based on different thiadiazoloquinoxaline acceptor units for efficient polymer solar cells
-
Two low bandgap D-A1-D-A2 conjugated copolymers, namely denoted as P1 (non-fluorine substituted thiadiazoloquinoxaline A2) and P2 (fluorine substituted thiadiazoloquinoxaline A2) with the same D (thiophene) and A1 (benzothiadiazole) groups were synthesize
- Keshtov,Kuklin,Radychev,Ostapov,Nikolaev,Konstantinov,Krayushkin,Koukaras,Sharma, Abhishek,Sharma
-
p. 71232 - 71244
(2016/08/05)
-
- Efficient palladium-catalyzed C(sp2)-H activation towards the synthesis of fluorenes
-
A facile protocol for the synthesis of fluorene derivatives has been developed through palladium-catalyzed cyclization of 2′-halo-diarylmethanes via activation of arylic C-H bonds. The reactions occurred smoothly and allowed both electron-rich and electron-deficient substrates to convert into their corresponding fluorenes in good to excellent yields. Studies revealed that this Pd-catalyzed cyclization was also available for the substrates of 2′-chloro-diarylmethanes and no catalyst poisoning occurred for 2′-iodo-diphenylmethane.
- Song, Juan,Li, Yali,Sun, Wei,Yi, Chenglong,Wu, Hao,Wang, Haotian,Ding, Keran,Xiao, Kang,Liu, Chao
-
p. 9030 - 9033
(2016/11/11)
-
- Halogen-Adjusted Chemoselective Synthesis of Fluorene Derivatives with Position-Controlled Substituents
-
Fluorenes have been synthesized through an efficient novel Pd-catalyzed tandem cross-coupling reaction; these substrates are fascinating building blocks found in organic photoelectric materials. The position of the substituent on fluorenes could be conveniently tuned by changing the halogen in the ortho-halobenzyl bromide substrates when coupled with various arylboronic acids. This newly developed synthetic approach could achieve the potential diversity in fluorene-based molecular architectures.
- Song, Juan,Sun, Wei,Li, Yali,Wei, Fuliang,Liu, Chao,Qian, Yan,Chen, Shufen
-
supporting information
p. 211 - 215
(2016/03/01)
-
- Pd(0)-Catalyzed Cross-Coupling of 1,1-Diboronates with 2,2′-Dibromobiphenyls: Synthesis of 9H-Fluorenes
-
An efficient and mild synthesis of 9H-fluorene derivatives through a Pd(0)-catalyzed cross-coupling reaction of 1,1-diboronates with 2,2′-dibromobiphenyls has been developed. This reaction features high yields, operational simplicity, and mild reaction conditions, thus providing an excellent alternative to published methods for 9H-fluorene synthesis.
- Xu, Shuai,Shangguan, Xianghang,Li, Huan,Zhang, Yan,Wang, Jianbo
-
p. 7779 - 7784
(2015/08/18)
-
- Br?nsted acid-mediated intramolecular cyclization of biaryl triazenes for the synthesis of fluorenes and 9,10-dihydro-phenanthrenes
-
The efficient synthesis of fluorenes from biaryl triazenes is successfully developed. Up to 27 examples of biaryl triazenes are converted into their corresponding fluorene derivatives in the presence of CF3COOH (4.0 equiv). Mechanism research i
- Xu, Lijun,Yang, Weijun,Zhang, Lili,Miao, Maozhong,Yang, Zhigen,Xu, Xin,Ren, Hongjun
-
p. 9206 - 9221
(2015/01/08)
-
- Pd-catalyzed nucleophilic fluorination of aryl bromides
-
On the basis of mechanism-driven reaction design, a Pd-catalyzed nucleophilic fluorination of aryl bromides and iodides has been developed. The method exhibits a broad substrate scope, especially with respect to nitrogen-containing heteroaryl bromides, and proceeds with minimal formation of the corresponding reduction products. A facilitated ligand modification process was shown to be critical to the success of the reaction.
- Lee, Hong Geun,Milner, Phillip J.,Buchwald, Stephen L.
-
supporting information
p. 3792 - 3795
(2014/04/03)
-
- Synthesis of fluorene and indenofluorene compounds: Tandem palladium-catalyzed suzuki cross-coupling and cyclization
-
Figure Presented "Fluor" it: Palladium-catalyzed tandem reactions, in which C(sp3)-H bond activation is the key step (see scheme; DMA = dimethylacetamide), lead to substituted fluorenes and indenofluorenes through annulation in high yield and i
- Liu, Tao-Ping,Xing, Chun-Hui,Hu, Qiao-Sheng
-
supporting information; experimental part
p. 2909 - 2912
(2010/08/04)
-
- Highly efficient and versatile synthesis of polyarylfluorenes via Pd-catalyzed C-H bond activation
-
A facile protocol for the Pd-catalyzed preparative synthesis of fluorene derivatives has been developed. While a wide range of fluorenes were easily obtained with high efficiency and selectivity under mild conditions, excellent functional group tolerance
- Hwang, Seung Jun,Kim, Hyun Jin,Chang, Sukbok
-
supporting information; experimental part
p. 4588 - 4591
(2009/12/09)
-
- Fluorination of fluorene, dibenzofuran and their open analogues with caesium fluoroxysulfate and related fluorinating reagents
-
Fluorination of fluorene (1) with caesium fluoroxysulfate (CFS), 2,6-dichloro-l-fluoropyridinium tetrafluoroborate (FP-B800) and 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]-octane bis(tetrafluoroborate) (Accufluor NFTh) occurred only on the aromatic ring in the position ortho and para to the biphenyl central bond with the ratio 2-fluoro- (2a) vs 4-fluorofluorene (2b) 1.7-2.4:1. Regioselectivity of fluorination of both open-chain analogues - diphenylmethane (3a) and biphenyl (3b) was different and more ortho-fluorinated product was formed. Furthermore, the reaction of diphenylmethane (3a) with CFS occurred also on central carbon forming benzophenone (6) and fluorodiphenylmethane (7), while fluorination with FP-B800 and Accufluor NFTh occurred only at the aromatic ring. Similar effect of the structure of fluorinating reagent on the regioselectivity was also observed with dibenzofuran (8) and its open-chain analogues diphenyl ether (10) and biphenyl (3b), where the regioselectivity of fluorination with CFS (1- (9a):2- (9b):3- (9c) = 27:46:27) was similar to fluorination with Selectfluor. Product distribution of fluorination of fluorene (1) and dibenzofuran (8) with CFS is similar to nitration and is in accordance with the calculated HOMO electron density, which indicates the presence of the electron transfer pathway.
- Iskra, Jernej,Stavber, Stojan,Zupan, Marko
-
experimental part
p. 1671 - 1680
(2009/05/27)
-
- Low-valent niobium-mediated double activation of C-F/C-H bonds: Fluorene synthesis from o-arylated α,α,α-trifluorotoluene derivatives
-
By the treatment of 0.3 molar amount of NbCl5 and LiAlH4, o-arylated α,α,α-trifluorotoluenes afforded fluorene derivatives in good yields. C-F bonds of the CF3 group and the neighboring ortho C-H bond were doubly activated to give the coupling products. Copyright
- Fuchibe, Kohei,Akiyama, Takahiko
-
p. 1434 - 1435
(2007/10/03)
-
- The role of geometry on regioselectivity and rate of fluorination of fluorene and diphenylmethane with selectfluor F-TEDA-BF4
-
Diphenylmethane and fluorene were used as target molecules in an investigation of the effect of the geometry of aromatic molecules on the regioselectivity and rate of fluorination with 1-chloromethyl-4-fluoro-1,4-diazonia-bicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor F-TEDA-BF4). In acetonitrile at 80°C ring fluorination of diphenylmethane was accompanied by oxidation of the saturated carbon atom, while in trifluoroacetic acid only ring fluorination with an ortho-para regioselectivity of 1.8:1 was observed. Fluorene was converted in acetonitrile as well as in trifluoroacetic acid into 2- and 4-fluoro substituted products in the relative ratio of 2:1 and 1.2:1, respectively. The reactions in acetonitrile obey a simple rate equation: v = d[F-TEDA]/dt=k2 × [F-TEDA] × [Substrate] and the second order rate constants for the reactions in acetonitrile at 65°C were determined; values of 0.6 × 10-4 M-1 s-1 for diphenylmethane and 35.5 × 10-4 M-1 s-1 for fluorene were obtained. The reaction rates for the various functionalisations of fluorene relative to those for diphenylmethane were found to be considerably influenced by the type of functionalisation. Relative rate factors (krel=k2(fluorene)/k2(diphenylmethane)) with values between 59 for fluorination and 712 for chlorination were determined, while the corresponding data for the biphenyl/diphenylmethane pair were only slightly dependent on the type of functionalisation. A reaction pathway involving electron transfer, thus forming cation radical intermediates, was proposed as the main process in the case of fluorination of fluorene with F-TEDA-BF4.
- Iskra, Jernej,Zupan, Marko,Stavber, Stojan
-
p. 1528 - 1531
(2007/10/03)
-
- Spirotricyclic substituted azacycloalkane derivatives and uses thereof
-
Spirotricyclic azacycloalkyl compounds and pharmaceutically acceptable salts thereof are disclosed. The synthesis of these compounds is also described. One application of these compounds, which are alpha 1a adrenergic receptor antagonists, is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.
- -
-
-
- Treatment of diabetic complications with certain spiro-imidazolidine-diones
-
Inhibition of aldose reductase activity with tetracyclic spiro-hydantoins, new tetracyclic spirohydantoin derivatives useful in the treatment of complications arising from diabetes mellitus, and a process for preparing spiro-imidazolidine-diones by reacting a mono- or di-fluorofluorene with an excess of oxygen and a tetralkyl- or arylalkyl-trialkyl-ammonium hydroxide are disclosed.
- -
-
-
- Method of inhibiting aldose reductase activity
-
Inhibition of aldose reductase activity with tetracyclic spiro-hydantoins.
- -
-
-
- Hydantoin derivatives for use in inhibiting aldose reductase activity, compositions therefor and process for preparing spiro-fluoren compounds
-
Inhibition of aldose reductase activity with tetracyclic spiro-hydantoins, new tetracyclic spirohydantoin derivatives useful in the treatment of complications arising from diabetes mellitus, and a process for preparing spiro-imidazolidine-diones by reacting a mono- or di-fluorofluorene with an excess of oxygen and a tetralkyl- or arylalkyl-trialkyl-ammonium hydroxide are disclosed
- -
-
-