Iron-Catalyzed Intermolecular Oxyamination of Terminal Alkenes Promoted by HFIP Using Hydroxylamine Derivatives

An atom-economical intermolecular iron-catalyzed oxyamination of alkenes is described herein. The insertion of oxygenated and nitrogenated moieties from the hydroxylamine substrate was observed with full regio- and chemo-selectivity for terminal alkenes in good yields. HFIP as a solvent appeared to have a synergistic effect with the iron catalyst to promote the formation of the oxyaminated products. Preliminary mechanistic studies suggest a pathway going through an aziridination reaction followed by an in situ ring opening

Development of a One-Pot Four C–C Bond-Forming Sequence Based on Palladium/Ruthenium Tandem Catalysis

A one-pot four C–C bond-forming sequence has been developed using two distinct transition metal complexes. The sequence entails a double Pd-catalyzed allylic alkylation followed by a Ru-catalyzed ring-closing metathesis and a Pd-catalyzed Heck coupling. The use of various active methylene nucleophiles was examined with yields up to 76% (93% per C–C bond)

Enantioselective Synthesis of 1-Aryl-tetrahydroisoquinolines through Iridium Catalyzed Asymmetric Hydrogenation

Asymmetric hydrogenation of 1-aryl-3,4-dihydroisoquinolines using the [IrCODCl]₂/(<i>R</i>)-3,5-diMe-Synphos catalyst is reported. Under mild reaction conditions, this atom-economical process provides easy access to a variety of enantioenriched 1-aryl-1,2,3,4-tetrahydroisoquinoline derivatives, which are important pharmacophores found in several pharmaceutical drug candidates, in high yields and enantiomeric excesses up to 99% after a single crystallization

Palladium-Catalyzed Efficient Enantioselective Synthesis of Chiral Allenes: Steric and Electronic Effects of Ligands

Asymmetric synthesis of chiral allenes starting from prochiral substrates under mild reaction conditions promoted by Pd-SYNPHOS catalyst is reported. This protocol provides an efficient access to various enantioenriched aryl- and alkyl- substituted allenes, which are versatile building blocks of high utility to both organic and medicinal chemists, in excellent isolated yields (up to 96%) and high enatiomeric ratio values (up to 95:5). In addition, a comparative study using several <i>C</i>₂-symmetric atropisomeric diphosphine ligands revealed the overwhelming impact of the steric and electronic properties of the ligands for the catalytic efficiency of this process

Iron-Catalyzed Intramolecular C(sp³)‑H Lactonization of Hydroxamate Derivatives Promoted by a 1,5-HAT

An iron-catalyzed lactonization reaction via intramolecular C(sp3)-H functionalization is described. The process employs easily accessible hydroxamate derivatives from which the noncommon insertion of the oxygen occurred through a 1,5-hydrogen atom transfer. A mixture of water and hexafluoroisopropanol as solvent appeared to be the key parameter of this transformation to reach a high selectivity and efficiency

General Asymmetric Hydrogenation of 2-Alkyl- and 2-Aryl-Substituted Quinoxaline Derivatives Catalyzed by Iridium-Difluorphos: Unusual Halide Effect and Synthetic Application

A general asymmetric hydrogenation of a wide range of 2-alkyl- and 2-aryl-substituted quinoxaline derivatives catalyzed by an iridium–difluorphos complex has been developed. Under mild reaction conditions, the corresponding biologically relevant 2-substituted-1,2,3,4-tetrahydroquinoxaline units were obtained in high yields and good to excellent enantioselectivities up to 95%. With a catalyst ratio of S/C = 1000 and on a gram scale, the catalytic activity of the Ir–difluorphos complex was maintained showing its potential value. Finally, we demonstrated the application of our process in the synthesis of compound (<i>S</i>)-<b>9</b>, which is an inhibitor of cholesteryl ester transfer protein (CETP)

General Asymmetric Hydrogenation of 2-Alkyl- and 2-Aryl-Substituted Quinoxaline Derivatives Catalyzed by Iridium-Difluorphos: Unusual Halide Effect and Synthetic Application

A general asymmetric hydrogenation of a wide range of 2-alkyl- and 2-aryl-substituted quinoxaline derivatives catalyzed by an iridium–difluorphos complex has been developed. Under mild reaction conditions, the corresponding biologically relevant 2-substituted-1,2,3,4-tetrahydroquinoxaline units were obtained in high yields and good to excellent enantioselectivities up to 95%. With a catalyst ratio of S/C = 1000 and on a gram scale, the catalytic activity of the Ir–difluorphos complex was maintained showing its potential value. Finally, we demonstrated the application of our process in the synthesis of compound (<i>S</i>)-<b>9</b>, which is an inhibitor of cholesteryl ester transfer protein (CETP)

General Asymmetric Hydrogenation of 2-Alkyl- and 2-Aryl-Substituted Quinoxaline Derivatives Catalyzed by Iridium-Difluorphos: Unusual Halide Effect and Synthetic Application

A general asymmetric hydrogenation of a wide range of 2-alkyl- and 2-aryl-substituted quinoxaline derivatives catalyzed by an iridium–difluorphos complex has been developed. Under mild reaction conditions, the corresponding biologically relevant 2-substituted-1,2,3,4-tetrahydroquinoxaline units were obtained in high yields and good to excellent enantioselectivities up to 95%. With a catalyst ratio of S/C = 1000 and on a gram scale, the catalytic activity of the Ir–difluorphos complex was maintained showing its potential value. Finally, we demonstrated the application of our process in the synthesis of compound (<i>S</i>)-<b>9</b>, which is an inhibitor of cholesteryl ester transfer protein (CETP)