A combination of experimental and computational studies have identified a C=O⋅⋅⋅isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200). The reaction proceeds at low catalyst loadings (generally 1 mol %) with either isobutyric or acetic anhydride as the acylating agent under mild conditions.

Supramolecular anion receptors can be used to study the molecular recognition properties of the reactive yet biologically critical hydrochalcogenide anions (HCh–). Achieving selectivity for HCh– over the halides is challenging but necessary for not only developing future supramolecular probes for HCh– binding and detection, but also for understanding the fundamental properties that govern these binding and recognition events. Here we demonstrate that linear free energy relationships (LFERs)including Hammett and Swain–Lupton plotsreveal a clear difference in sensitivity to the polarity of an aryl C–H hydrogen bond (HB) donor for HS– over other HCh– and halides. Analysis using electrostatic potential maps highlights that this difference in sensitivity results from a preference of the aryl C–H HB donor for HS– in this host scaffold. From this study, we demonstrate that LFERs are a powerful tool to gain interpretative insight into motif design for future anion-selective supramolecular receptors and highlight the importance of C–H HB donors for HS– recognition. From our results, we suggest that aryl C–H HB donors should be investigated in the next generation of HS– selective receptors based on the enhanced HS– selectivity over other competing anions in this system.

Rationally designed phosphaquinolinone derivatives containing electron-donating and/or -withdrawing groups are reported, with dimerization constants up to 525 M−1.

The first highly selective catalytic hydroboration of alkyl-substituted aldimines to provide medicinally relevant α-amidoboronates is disclosed. The Cu(I)-catalyzed borylation proceeds with excellent facial selectivity when a set of planar-chiral N-heterocyclic carbenes (NHCs) were employed as ligands. Density functional theory computations suggest that interactions between BPin and the planar-chiral catalyst are responsible for the observed stereoselectivity. Important pharmacophores, such as the boronate analogue of isoleucine, can be prepared using a chromatography-free protocol starting from commercially available reagents. The application of these NHC ligands in these Cu(I)-catalyzed processes offers a significant contribution to existing strategies for laboratory-scale preparation of enantioenriched α-amidoboronates.

Herein, the synthesis of 1,2,3,4-tetrasubstituted benzenoid rings, motifs found in pharmaceutical,a grochemical, and natural products, is described. [1] In the past, the regioselective syntheses of such compounds have been as ignificant challenge. This work reports am ethod using substituted arynesd erived from aryl(Mes)iodonium salts to access ar ange of densely functionalized 1,2,3,4-tetrasubstituted benzenoid rings. Significantly, it was found that halide substituents are compatible under these conditions, enabling post-synthetic elaboration via palladium-catalyzed coupling. This concise strategy is predicated on two regioselective events:1 )ortho-d eprotonation of aryl(Mes)iodonium salts to generate as ubstituted aryne intermediate, and 2) regioselective trapping of said arynes, thereby improving previously reportedr eaction conditions to generatea rynes at room temperature and in shorter reaction times. Density functional theory (DFT) computations and linear free energy relationship (LFER) analysis suggest the regioselectivity of deprotonation is influenced by both proximal and distal ring substituents on the aryne precursor.Ac ompetition experiment furtherr eveals the role of arene substituents on relative reactivity of aryl(Mes)iodoniums as aryne precursors.Scheme1.Selectedexamples and retrosynthesis of 1,2,3,4-substituted benzenoid rings.

A combination of experimental and computational studies have identified a C=O•••isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s up to > 200). The reaction proceeds at low catalyst loadings (generally 1 mol%) using either isobutyric or acetic anhydride as the acylating agent under mild conditions.

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We describe a strategy for the iodane-guided functionalization of sterically congested C-H bonds, which is distinct from electronic, steric or proximity guided C-H functionalization methods. Readily accessible aryl(Mes)iodonium salts serve as the starting materials in these reactions and produce complex 1,2,3,4-substituted arenes via aryne intermediates. This approach is especially powerful when coupled with the innate C-H functionalization reactivity of simple arenes, to replace two C-H bonds with two C-C or C-heteroatom bonds while over-riding steric effects that typically inhibit such reactions. DFT stud-ies reveal a contribution of inductive, resonance, and steric effects on the regioselectivity of C-H cleavage and aryne generatation.