Chiral Ligands Based on Binaphthyl Scaffolds for Pd-Catalyzed Enantioselective C-H Activation/Cycloaddition Reactions.

We report the first examples of the use of a new class of ligands (NOBINAc) for performing asymmetric C-H activations using palladium catalysts. These ligands combine the axial chirality of binaphthyl scaffolds with the bifunctional and bidentate coordination properties of mono-N-protected amino acids (MPAAs), which are well-known to favor Pd-promoted C-H activations via concerted metalation-deprotonation mechanisms. We demonstrate that our new ligands enable substantially higher enantioselectivities than MPAAs in the assembly of 2-benzazepines through formal (5 + 2) cycloadditions between homobenzyltriflamides or o-methylbenzyltriflamides and allenes.

Palladium-Catalyzed, Enantioselective Formal Cycloaddition between Benzyltriflamides and Allenes: Straightforward Access to Enantioenriched Isoquinolines.

Benzyl and allyltriflamides can engage in Pd-catalyzed oxidative (4+2) annulations with allenes, to produce highly valuable tetrahydroisoquinoline or dihydropyridine skeletons. The reaction is especially efficient when carried out in the presence of designed N-protected amino acids as metal ligands. More importantly, using this type of chiral ligands, it is possible to perform desymmetrizing, annulative C-H activations of prochiral diarylmethylphenyl amides, and thus obtain the corresponding isoquinolines with high enantiomeric ratios.

Screening for Polar Chemicals in Water by Trifunctional Mixed-Mode Liquid Chromatography-High Resolution Mass Spectrometry.

The presence of persistent and mobile organic contaminants (PMOC) in aquatic environments is a matter of high concern due to their capability of crossing through natural and anthropogenic barriers, even reaching drinking water. Most analytical methods rely on reversed-phase liquid chromatography (RPLC), which is quite limited for the detection of very polar chemicals. Thus, many of these PMOCs may have not been recognized as water pollutants yet, due to the lack of analytical methods capable to detect them. Mixed-mode LC (MMLC), providing the combination of RP and ion-exchange functionalities is explored in this work with a trifunctional column, combining RPLC, anion and cation exchange, which allows the simultaneous determination of analytes with extremely different properties. A nondiscriminant sample concentration step followed by a MMLC-high resolution mass spectrometry method was developed for a group of 37 very polar model chemicals with different acid/base functionalities. The overall method performance was satisfactory with a mean limit of detection of 50 ng/L, relative standard deviation lower than 20% and overall recoveries (including matrix effects) higher than 60% for 54% of model compounds. Then, the method was applied to 15 real water samples, by a suspect screening approach. For those detected PMOC with standard available, a preliminary estimation of concentrations was also performed. Thus, 22 compounds were unequivocally identified in a range of expected concentrations from 6 ng/L to 540 µg/L. Some of them are well-known PMOC, such as acesulfame, perfluorobutanoic acid or metformin, but other novel pollutants were also identified, as for example di-o-tolylguanidine or trifluoromethanesulfonic acid, which had not or were scarcely studied in water so far.

Assembly of Tetrahydroquinolines and 2-Benzazepines by Pd-Catalyzed Cycloadditions Involving the Activation of C(sp3)-H Bonds.

Cycloaddition reactions are among the most practical strategies to assemble cyclic products; however, they usually require the presence of reactive functional groups in the reactants. Here, we report a palladium-catalyzed formal (4 + 2) cycloaddition that involves the activation of C(sp3)-H bonds and provides a direct, unconventional entry to tetrahydroquinoline skeletons. The reaction utilizes amidotolyl precursors and allenes as annulation partners, and is catalyzed by Pd(II) precursors in combination with specific N-acetylated amino acid ligands. The reactivity can be extended to ortho-methyl benzylamides, which provide for the assembly of appealing tetrahydro-2-benzazepines in a formal (5 + 2) annulation process.