A highly regio, diastereo-and enantioselective, scalable Ir-catalyzed hydroarylation of electron rich acyclic and tensioned cyclic olefins with heterobiaryls is described. The reaction of acyclic vinyl ethers, dihydrofuran and norbornenes with a variety of aryl isoquinoline, quinazoline, and picoline derivatives takes place with simultaneous installation of central and axial chirality, reaching complete branched/linear or exo/endo ratios and excellent diastereo-and enantiomeric excesses when in situ formed [Ir I /Tol-SDP] or [Ir I /Tol-BINAP] complexes are used as the catalysts. Kinetic isotope effect (KIE) analyses and a comprehensive computational study suggest that, despite fast double bond migratory insertion into Ir-H, the reaction proceeds through a modified Chalk-Harrod mechanism, starting with selectivity-determining insertion into Ir-CAryl. The regioselectivity is controlled by the electron donating alkoxy group, whereas diastereo-and enantioselectivity have a complex origin, that depend on the relative orientation of the alkoxy group and the establishment of adequate π-π interactions between the biaryl and the phosphine. ASSOCIATED CONTENT Supporting Information. Experimental procedures and characterization data for new compounds, crystallographic data for (Sa,R)-9b, (Ra,S)-7g and (Ra,R,R,S) 16h, and HPLC traces for compounds 7-11, 15-17. Additional computational details. XYZ coordinates of calculated species. This material is available free of charge via the Internet at http://pubs.acs.org.

The Pd 0 -catalyzed coupling of racemic heterobiaryl bromides, triflates or nonaflates with aryl/alkyl primary amines using QUINAP as the ligand provides the corresponding axially chiral heterobiaryl amines with excellent yields and enantioselectivities. Reactivity and structural studies of neutral and cationic oxidative addition intermediates support a dynamic kinetic asymmetric amination mechanism based on the labilization of the stereogenic axis in the latter, and suggest that coordination of the amine to the Pd center is the stereodetermining step.In recent years, significant advances have been achieved in the field of asymmetric cross-coupling, in particular for the synthesis of axially chiral biaryls.1 In sharp contrast, the direct asymmetric heteroaryl-aryl cross-coupling remains as an unmet challenge, 2 limiting the access to functionalized heterobiaryls with appealing structures for their use as ligands in asymmetric catalysis. As a remarkable example, the use Isoquinoline-Amino Naphthalene (IAN) and related derivatives, which can be seen as N(sp 2 ),N(sp 3 ) analogues of QUINAP, have been scarcely investigated.3 A plausible explanation is the poor availability: there are no commercially available representatives and their synthesis still requires chromatographic separation of diastereomeric mixtures (Scheme 1, eq. 1), 4 while the lack of a general and practical method of synthesis has also limited the structural diversity of known ligands of this type. Recently, we have reported a novel strategy for the synthesis of functionalized heterobiaryls based on dynamic kinetic asymmetric C-C 5 and C-P 6 bond formations starting from heterobiaryl triflates to ensure the formations of cationic oxidative addition intermediates (Scheme 1, eq. 2). Stimulated by the growing potential of related axially chiral heterobidentate ligands, 7 we decided to focus on the development of dynamic kinetic Buchwald-Hartwig (DYKAT: Dynamic Kinetic Asymmetric Transformation) amination of heterobiaryl electrophiles for the asymmetric synthesis of axially chiral IAN-type diamines (Scheme 1, eq. 3).The unprecedented asymmetric amination of heterobiaryls is a particularly challenging goal due to the specific conditions required. First, a strong base is generally needed to achieve good reactivities, so that compatibility issues might arise with the heteroScheme 1. Synthetic approaches to IAN amines biaryl triflates used in previous DYKAT processes. Second, the racemization barriers for IAN amines are significantly lower than those of arylated products I or QUINAP-type products II, 8 making necessary to work under exceptionally mild conditions. 9 In order to minimize the hydrolysis of the starting material, we started using the coupling between nonaflate (±)-1A 10 and aniline 5a as a model reaction for the synthesis of IAN 6Aa, using NaOtBu as the base, dry toluene as the solvent at 60 °C and 10 mol% Pd(dba)2/12 mol% ligand as the catalyst system (Scheme 2).Ligands that showed a good performance in related processes were select...

Seven tetracoordinate organoboron fluorophores with heterobiaryl N,O- or N,N-chelate ligands were prepared and photophysically characterized (in toluene). The electronic variation of the heteroaromatic moiety provided a means for the fine-tuning of the UV/vis absorption and emission spectra. In the most interesting cases, the spectra were red-shifted to maximum absorbance at wavelengths longer than 500 nm and emission maxima between 620 and 660 nm. The pronounced intramolecular charge-transfer character of the dyes yielded large Stokes shifts (3500-5100 cm), while maintaining appreciable fluorescence quantum yields of up to 0.2 for emission maxima longer than 600 nm. The lipophilic character of the dyes enabled their application as stains of vesicle substructures in confocal fluorescence microscopy imaging.

The catalytic hydroarylation of alkynes has emerged as an excellent methodology for the synthesis of functionalized alkenes with excellent levels of regio- and stereocontrol (syn). However, in spite of the great progress in this field, the number of asymmetric methodologies is still scarce. Herein, we report an atroposelective Ir-catalyzed C–H hydroarylation of alkynes, which enables the asymmetric synthesis of axially chiral heterobiaryl trisubstituted olefins in good to high yields and enantioselectivities up to 98% ee.

Two four‐coordinate organoboron N,C‐chelate complexes with different functional terminals on the PEG chains are studied with respect to their photophysical properties within human MCF‐7 cells. Their excited‐state properties are characterized by time‐resolved pump‐probe spectroscopy and fluorescence lifetime microscopy. The excited‐state relaxation dynamics of the two complexes are similar when studied in DMSO. Aggregation of the complexes with the carboxylate terminal group is observed in water. When studying the light‐driven excited‐state dynamics of both complexes in cellulo, i. e., after being taken up into human MCF‐7 cells, both complexes show different features depending on the nature of the anchoring PEG chains. The lifetime of a characteristic intramolecular charge‐transfer state is significantly shorter when studied in cellulo (360±170 ps) as compared to in DMSO (∼960 ps) at 600 nm for the complexes with an amino group. However, the kinetics of the complexes with the carboxylate group are in line with those recorded in DMSO. On the other hand, the lifetimes of the fluorescent state are almost identical for both complexes in cellulo. These findings underline the importance to evaluate the excited‐state properties of fluorophores in a complex biological environment in order to fully account for intra‐ and intermolecular effects governing the light‐induced processes in functional dyes.