164172-87-6Relevant articles and documents
The site-selectivity and mechanism of Pd-catalyzed C(sp2)-H arylation of simple arenes
Kim, Daeun,Choi, Geunho,Kim, Weonjeong,Kim, Dongwook,Kang, Youn K.,Hong, Soon Hyeok
, p. 363 - 373 (2021/01/14)
Control over site-selectivity is a critical challenge for practical application of catalytic C-H functionalization reactions in organic synthesis. Despite the seminal breakthrough of the Pd-catalyzed C(sp2)-H arylation of simple arenes via a concerted metalation-deprotonation (CMD) pathway in 2006, understanding the site-selectivity of the reaction still remains elusive. Here, we have comprehensively investigated the scope, site-selectivity, and mechanism of the Pd-catalyzed direct C-H arylation reaction of simple arenes. Counterintuitively, electron-rich arenes preferably undergo meta-arylation without the need for a specifically designed directing group, whereas electron-deficient arenes bearing fluoro or cyano groups exhibit high ortho-selectivity and electron-deficient arenes bearing bulky electron-withdrawing groups favor the meta-product. Comprehensive mechanistic investigations through a combination of kinetic measurements and stoichiometric experiments using arylpalladium complexes have revealed that the Pd-based catalytic system works via a cooperative bimetallic mechanism, not the originally proposed monometallic CMD mechanism, regardless of the presence of a strongly coordinating L-type ligand. Notably, the transmetalation step, which is influenced by a potassium cation, is suggested as the selectivity-determining step.
Synthesis of a class of binaphthyl monophosphine ligands with a naphthofuran skeleton and their applications in Suzuki-Miyaura coupling reactions
Zhou, Zihong,Liang, Hao,Xia, Wang,Chen, Huixuan,Zhang, Yaqi,He, Xuefeng,Yu, Sifan,Cao, Rihui,Qiu, Liqin
, p. 5967 - 5971 (2018/04/23)
A series of new monophosphine ligands containing a naphthofuran skeleton have been prepared, characterized and evaluated in palladium-catalyzed Suzuki-Miyaura coupling reactions. Using Pd2(dba)3-L6 as the catalyst the reactions were performed with high catalytic activity under mild reaction conditions and the desired coupling products were obtained in good to excellent yields. The new catalyst system also showed broad substrate adaptability and practicality for gram-scale production.
Potent, Orally Active, Competitive N-Methyl-D-aspartate (NMDA) Receptor Antagonists Are Substrates for a Neutral Amino Acid Uptake System in Chinese Hamster Ovary Cells
Li, Jia-He,Bigge, Christopher F.,Williamson, Rufus M.,Borosky, Susan A.,Vartanian, Mark G.,Ortwine, Daniel F.
, p. 1955 - 1965 (2007/10/02)
A series of enantiomerically pure (phosphonomethyl)-substituted phenylalanine derivatives related to SDZ EAB 515 (1) were prepared as competitive N-methyl-D-aspartate (NMDA) receptor antagonists.Unlike most known competitive NMDA antagonists, analogs in this series with the S-configuration are potent NMDA antagonists whereas analogs with the unnatural R-configuration are weak NMDA antagonists, as determined by receptor binding experiments and their anticonvulsant action in mice.Examination in a previously reported competitive NMDA pharmacophore model revealed that receptor affinity can be explained partially by a cavity that accommodates the biphenyl ring of 1, while the biphenyl ring of the R-enantiomer 2 extends into a disallowed steric region.We proposed that analogs with the natural S-configuration and a large hydrophobic moiety would have an advantage in vivo over analogs with an R-configuration by being able to use a neutral amino acid uptake system to enhance both peripheral adsorption and transport into the brain.Examination in a system L neutral amino acid transport carrier assay shows that 1 competes with L-Phe for transport in an apparent competitive and stereospecific manner (estimated Ki=50 μM).The 1- and 2-naphthyl derivatives 3a,3b were found to be among the most potent, competitive NMDA antagonists yet discovered, being ca. 15-fold more potent than 1 in vitro and in vivo, with a long duration of action.The title compound 3a had potent oral activity in MES (ED50=5.0 mg/kg). 3a also retains its ability to compete, albeit more weakly than 1 (estimated Ki=200 μM), for L-Phe uptake to CHO cells.In this series, analogs with the R-configuration are not substrates for the system L neutral amino acid transport carrier.These results provide evidence that central nervous system active agents can be designed as substrates of a neutral amino acid transporter as a means to enhance penetration of the blood-brain barrier.
