116757-85-8Relevant articles and documents
Effect of solvent polarity on the regioselective hydroxyalkylation of indole with trifluoroacetaldehyde hemiacetals
Peerannawar, Swarada,Sood, Abha,Brown, Alicia,Sch?fer, Christian,Alonzo, Judith,Sutton, Steven,Christianson, Matthew,Stocking, Raven,Naclerio, Nicole,T?r?k, Béla,Landge, Shainaz M.
, p. 1941 - 1956 (2019)
The effect of solvents has been found as a crucial factor in determining the regioselectivity of the hydroxyalkylation of indole with trifluoroacetaldehyde hemiacetals. The appropriate selection of the solvent ensured to achieve absolute N1 or C3 regio/chemoselectivity of the reaction depending on the polarity and dielectric constant of the medium. Reaction conditions were optimized considering the effect of solvent, including temperature, time, and molar ratio of reactants to base. In order to rationalize this effect, density functional theory has been employed in which implicit as well as explicit role of solvent was studied, which were further validated with in situ 1H NMR spectroscopy experiments. The comparison of transition states derived from the implicit calculations revealed that the lowest energy path of the reaction in dimethyl sulfoxide (DMSO) leads to product formation with N-selectivity. Further DFT calculations on explicit interactions of indole with DMSO indicated enhanced nucleophilicity on the N atom compared to that of C3 atom, which is evident from the calculated electrostatic potential (ESP) fit charges of these complexes. These findings appear to support the experimental data and explain the N-selectivity in DMSO.
Microwave-assisted preparation of trifluoroacetaldehyde (fluoral): isolation and applications
Landge, Shainaz M.,Borkin, Dmitry A.,T?r?k, Béla
, p. 6372 - 6376 (2007)
A novel method for the preparation of trifluoroacetaldehyde (fluoral, TFAc, CF3CHO) from commercially available trifluoroacetaldehyde ethylhemiacetal (TFAE) by microwave irradiation is described. The isolation, characterization and reaction of fluoral with various nucleophiles were studied to verify the diverse applicability of this new method.
Enzyme-catalyzed kinetic resolution of 2,2,2-trifluoro-1-(heteroaryl)ethanols: Experimental and docking studies
Kucher, Olexandr V.,Kolodiazhnaya, Anastasiya O.,Smolii, Oleg B.,Prisuazhnyk, Dmytro V.,Tolmacheva, Katerina A.,Zaporozhets, Olga A.,Moroz, Yurii S.,Mykhailiuk, Pavel K.,Tolmachev, Andrey A.
, p. 7692 - 7698 (2014)
A convenient approach towards enantiopure (R) and (S) isomers of 2,2,2-trifluoro-1-(heteroaryl)ethanols was developed. The enzyme-catalyzed kinetic resolution of the corresponding racemic mixtures was achieved by using a two-step protocol that involved an
THERMAL CONDENSATION OF INDOLES WITH TRIFLUOROACETALDEHYDE
Maki, Yasuo,Kimoto, Hiroshi,Fujii, Shozo,Senga, Munehiro,Cohen, Louis A.
, p. 47 - 60 (1988)
The title condensations provide the corresponding (1'-hydroxy-2',2',2'-trifluoroethyl)indoles.Indole itself, 1-methylindole and 2-methylindole gave 3-adducts in yields of 77percent, 49percent and 84percent, respectively. 3-Substituted indoles (3-methylindole, ethyl indole-3-acetate and indole-3-ethyl acetate) afforded 2-adducts in yields of 69percent, 21percent and 23percent, respectively.The indole adduct eliminates water at 137 deg C to form a transient 3-(trifluoromethylmethylene)indolenine, which reacts rapidly with nucleophiles including indole.
A Free-Radical-Promoted Site-Specific Cross-Dehydrogenative-Coupling of N-Heterocycles with Fluorinated Alcohols
Xu, Zhengbao,Hang, Zhaojia,Chai, Li,Liu, Zhong-Quan
, p. 4662 - 4665 (2016)
A C-C formation of an electron-rich N-heterocycle with fluorinated alcohol is developed. Through this radical-triggered cross-dehydrogenative coupling strategy, a wide range of useful building blocks such as C3 hydroxyfluoroalkylated indoles and pyrroles can be site-specifically synthesized. Mechanistic studies indicate a single-electron-transfer initiated radical cycle would be involved.
Mixed-Metal MIL-100(Sc,M) (M=Al, Cr, Fe) for Lewis acid catalysis and tandem C-C Bond formation and alcohol oxidation
Mitchell, Laura,Williamson, Patrick,Ehrlichov, Barbora,Anderson, Amanda E.,Seymour, Valerie R.,Ashbrook, Sharon E.,Acerbi, Nadia,Daniels, Luke M.,Walton, Richard I.,Clarke, Matthew L.,Wright, Paul A.
, p. 17185 - 17197 (2014)
The trivalent metal cations Al3+, Cr3+, and Fe3+ were each introduced, together with Sc3+, into MIL- 100(Sc,M) solid solutions (M=Al, Cr, Fe) by direct synthesis. The substitution has been confirmed by powder X-
TEMPO-Mediated Cross-Dehydrogenative Coupling of Indoles and Imidazo[1,2- a]pyridines with Fluorinated Alcohols
Nipate, Dhananjay S.,Jaspal, Sonam,Shinde, Vikki N.,Rangan, Krishnan,Kumar, Anil
, p. 1373 - 1377 (2021)
A simple and highly efficient metal-free method has been developed for hydroxyfluoroalkylation of indoles and imidazo[1,2-a]pyridines via TEMPO-mediated C(sp3)-H and C(sp2)-H bond cross-dehydrogenative coupling of fluorinated alcohols and indoles. The protocol showed broad substrate scope, afforded good yields of hydroxyfluoroalkylated products, and was amenable for scale-up. Mechanistic investigation indicated involvement of the radical pathway.
Environmentally benign, microwave-assisted chemoselective Nhydroxyalkylation of indoles with trifluoroacetaldehyde methyl hemiacetal
Sch?fer, Christian,Ellstrom, Clifford J.,Sood, Abha,Alonzo, Judith,Landge, Shainaz M.,Tran, Chris D.,T?r?k, Béla
, p. 122 - 130 (2017)
The chemoselective microwave-activated N-hydroxyalkylation of indoles using trifluoroacetaldehyde methylhemiacetal as the alkylating agent under mild conditions is described. The chemoselectivity of this reaction is determined by the solvent used. In dimethyl sulfoxide, the reaction occurs without the use of a strong base or a metal catalyst. This approach can be applied to a variety of different substituted indoles to obtain the corresponding N-alkylated products with high selectivity. The product 2,2,2-trifluoro-1-(1-H-indol-1-yl)ethanols combine two moieties of frequent pharmacological interest: the indole core and a CF3-group containing a hydroxyalkyl substituent.
High-throughput screening of bioactive compounds via new catalytic reaction in the pooled mixture
Satoh, Ayano,Nishina, Yuta
, (2019/08/20)
To increase the chances of finding new candidate molecules with medicinal properties, while expending less resource and effort, the present study used pooled substrates as starting materials. A bisindole compound that showed inhibitory activity was then isolated from the mixture, and the activity was improved by optimizing the substituents on the indole skeleton.
Asymmetric Hydrogenation of Aryl Perfluoroalkyl Ketones Catalyzed by Rhodium(III) Monohydride Complexes Bearing Josiphos Ligands
Brüning, Fabian,Nagae, Haruki,K?ch, Daniel,Mashima, Kazushi,Togni, Antonio
, p. 10818 - 10822 (2019/07/31)
The asymmetric hydrogenation of 2,2,2-trifluoroacetophenones and aryl perfluoroalkyl ketones was developed using a unique, well-defined chloride-bridged dinuclear rhodium(III) complex bearing Josiphos-type diphosphine ligands. These complexes were prepared from [RhCl(cod)]2, Josiphos ligands, and hydrochloric acid. As catalyst precursors, they allow for the efficient and enantioselective synthesis (up to 99 % ee) of chiral secondary alcohols with perfluoroalkyl groups. This system does not require an activating base for the hydrogenation of 2,2,2-trifluoroacetophenones. Additionally, the enantioselective C=O hydrogenations of 2-phenyl-3-(haloacetyl)-indoles, a class of privileged structures in medicinal chemistry, is reported for the first time.
