23037-39-0Relevant academic research and scientific papers
Synthesis of Functionalized Indolines and Dihydrobenzofurans by Iron and Copper Catalyzed Aryl C-N and C-O Bond Formation
Henry, Martyn C.,Senn, Hans Martin,Sutherland, Andrew
, p. 346 - 364 (2019/01/08)
A simple and effective one-pot, two-step intramolecular aryl C-N and C-O bond forming process for the preparation of a wide range of benzo-fused heterocyclic scaffolds using iron and copper catalysis is described. Activated aryl rings were subjected to a highly regioselective, iron(III) triflimide-catalyzed iodination, followed by a copper(I)-catalyzed intramolecular N-or O-arylation step leading to indolines, dihydrobenzofurans, and six-membered analogues. The general applicability and functional group tolerance of this method were exemplified by the total synthesis of the neolignan natural product, (+)-obtusafuran. DFT calculations using Fukui functions were also performed, providing a molecular orbital rationale for the highly regioselective arene iodination process.
Tripeptidic BACE1 inhibitors devised by in-silico conformational structure-based design
Hamada, Yoshio,Tagad, Harichandra D.,Nishimura, Yoshinori,Ishiura, Shoichi,Kiso, Yoshiaki
scheme or table, p. 1130 - 1135 (2012/03/26)
Previously reported pentapeptidic BACE1 inhibitors, designed using a substrate-based approach, were used as lead compounds for the further design of non-peptidic BACE1 inhibitors. Although these peptidic and non-peptidic inhibitors, with a hydroxymethylcarbonyl isostere as a substrate transition-state mimic, exhibited potent BACE1 inhibitory activities, their molecular-sizes appeared a little too big (molecular weight of >600 daltons) for developing practical anti-Alzheimer's disease drugs. To develop lower weight BACE1 inhibitors, a series of tripeptidic BACE1 inhibitors were devised using a design approach based on the conformation of a virtual inhibitor bound to the BACE1 active site, also called 'in-silico conformational structure-based design'. Although these tripeptidic BACE1 inhibitors contained some natural amino acid residues, they are expected to be useful as lead compounds for developing the next generation BACE1 inhibitors, due to their low molecular size and unique structural features compared with previously reported inhibitors.
Pd(II)-catalyzed hydroxyl-directed C-H olefination enabled by monoprotected amino acid ligands
Lu, Yi,Wang, Dong-Hui,Engle, Keary M.,Yu, Jin-Quan
supporting information; experimental part, p. 5916 - 5921 (2010/07/05)
A novel Pd(II)-catalyzed ortho-C-H olefination protocol has been developed using spatially remote, unprotected tertiary, secondary, and primary alcohols as the directing groups. Mono-N-protected amino acid ligands were found to promote the reaction, and an array of olefin coupling partners could be used. When electron-deficient alkenes were used, the resulting olefinated intermediates underwent subsequent Pd(II)-catalyzed oxidative intramolecular cyclization to give the corresponding pyran products, which could be converted into ortho-alkylated alcohols under hydrogenolysis conditions. The mechanistic details of the oxidative cyclization step are discussed and situated in the context of the overall catalytic cycle.
Temperature and Substituent Effects on Regioselectivity in the Insertion of Arylcarbene into Alcohols
Tomioka, Hideo,Suzuki, Shinji,Izawa, Yasuji
, p. 3156 - 3162 (2007/10/02)
Photolysis of aryldiazomethanes in methanol, ethanol, and 2-propanol gave OH insertion products along with small amounts of CH insertion products at ambient temperature.However, the CH insertion products increased significantly at the expense of the ether as the temperature was lowered.The attempted sensitized decomposition of the diazomethane did not lead to an increase in the CH insertion products presumably because of a rapid singlet-triplet equilibrium.The key intermediate leading to the CH insertion is suggested to be ground-state triplet arylcarbene, based on the accumulated spectroscopic as well as chemical evidence for the intervention of the triplet arylcarbene in the low-temperature photolysis of aryldiazomethanes.Substituents on the phenyl ring also have an appreciable effect on the insertion selectivity.At room temperature, the OH/CH insertion selectivity increased with the electron-donating ability of the substituents.This is interpreted in terms of the substituent effect on the transition state of OH insertion, where there is a deficiency of electrons at the benzylic carbon atom, rather than on the stability of singlet carbene.At low temperature, both electron-donating and -withdrawing substituents facilitate OH insertion, indicating the change in substituents induces a concomitant change in the insertion mechanism, presumably due to decreasing nucleophilicity of carbene with increasing electron-withdrawing ability as well as decreasing proton-donor activity of alcohol with decreasing temperature.This may also reflect the effect of the substituent on the singlet-triplet energy gap.
Effects of Substituents and Generation Methods on Insertion-Addition Selectivities of ''Arylcarbene'' in Alcohol-Olefin Binary Mixtures. Intervention of Reaction of Diazo Compounds Masquerading as Carbenes
Tomioka, Hideo,Suzuki, Shinji,Izawa, Yasuji
, p. 1047 - 1050 (2007/10/02)
A Hammett study of the insertion-addition selectivity (Ki/ka) and cyclopropanation stereoselectivity (kc/kt) of "arylcarbene" generated either photolytically or thermally in 2-propanol-ethyl vinyl ether binary mixtures showed that ρ values are highly sensitive to the generation method.Thus, plots of ki/ka and kc/kt vs. ? (?+) in the photolytic run gave ρ values of -0.96 (r = -0.96) and -0.15 (r = -0.95), respectively, whereas similar values are +1.4 (r = 0.93) and -1.1 (r = -0.96) in the thermal run.The results along with the effects of precursor, temperature, and sensitizer on the product distributions are interpreted as indicating that, while free carbene is involved in the photolytic run, the ground-state diazo compound is masquerading as carbene in its thermal reaction with the olefin.
