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 plotsreveal 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.
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