Project description:A new class of bis-cyclometalated iridium(III) catalysts containing two inert cyclometalated 6-tert-butyl-2-phenyl-2H-indazole bidentate ligands or two inert cyclometalated 5-tert-butyl-1-methyl-2-phenylbenzimidazoles is introduced. The coordination sphere is complemented by two labile acetonitriles, and a hexafluorophosphate ion serves as a counterion for the monocationic complexes. Single enantiomers of the chiral-at-iridium complexes (>99% er) are obtained through a chiral-auxiliary-mediated approach using a monofluorinated salicyloxazoline and are investigated as catalysts in the enantioselective conjugate addition of indole to an α,β-unsaturated 2-acyl imidazole and an asymmetric Nazarov cyclization.
Project description:The asymmetric isomerization of alkyne to allene is the most efficient and the completely atom-economic approach to this class of versatile axial chiral structure. However, the state-of-the-art is limited to tert-butyl alk-3-ynoate substrates that possess requisite acidic propargylic C-H bonds. Reported here is a strategy based on gold catalysis that is enabled by a designed chiral bifunctional biphenyl-2-ylphosphine ligand. It permits isomerization of alkynes with nonacidic α-C-H bonds and hence offers a much-needed general solution. With chiral propargylic alcohols as substrates, 2,5-disubstituted 2,5-dihydrofurans are formed in one step in typically good yields and with good to excellent diastereoselectivities. With achiral substrates, 2,5-dihydrofurans are formed with good to excellent enantiomeric excesses. A novel center-chirality approach is developed to achieve a stereocontrol effect similar to an axial chirality in the designed chiral ligand. The mechanistic studies established that the precatalyst axial epimers are all converted into the catalytically active cationic gold catalyst owing to the fluxional axis of the latter.
Project description:Atomically precise gold nanoclusters are ideal model catalysts with well-defined compositions and tunable structures. Determination of the ligand effect on catalysis requires the use of gold nanoclusters with protecting ligands as the only variable. Two isostructural Au38 nanoclusters, [Au38(L)20(Ph3P)4]2+ (L = alkynyl or thiolate), have been synthesized by a direct reduction method, and they have an unprecedented face-centered cubic (fcc)-type Au34 kernel surrounded by 4 AuL2 staple motifs, 4 Ph3P, and 12 bridging L ligands. The Au34 kernel can be derived from the fusion of two fcc-type Au20 via sharing a Au6 face. Catalytic performance was studied with these two nanoclusters supported on TiO2 (1/TiO2 and 2/TiO2) as catalysts. The alkynyl-protected Au38 are very active (>97%) in the semihydrogenation of alkynes (including terminal and internal ones) to alkenes, whereas the thiolated Au38 showed a very low conversion (<2%). This fact suggests that the protecting ligands play an important role in H2 activation. This work presents a clear demonstration that catalytic performance of gold nanoclusters can be modulated by the controlled construction of ligand spheres.
Project description:The single-step synthesis of fused tricyclic pyridazino[1,2-a]indazolium ring systems is described. Structural details revealed by crystallography explain the unexpected reactivity. The method is applied to the gram scale synthesis of nigeglanine hydrobromide.
Project description:Bifunctional ligand-enabled cooperative gold catalysis accelerates nucleophilic attacks and offers a versatile strategy to achieve asymmetric gold catalysis. Distinct from the prior studies employing alkyne/allene as the electrophilic site, this work engages an in situ-generated alkenyl/acyl gold carbene in a ligand-facilitated attack by an alcoholic nucleophile. With an amide-functionalized chiral binaphthylphosphine ligand, γ-alkoxy-α,β-unsaturated imides are formed with excellent enantiomeric excesses. The intermediacy of a carbene species is supported by its alternative access via dediazotization. The reaction tolerates a broad range of alcohols and can accommodate dienynamide substrates, in addition to arylenynamides. This work avails a versatile strategy to enrich gold chemistry and achieve challenging enantioselective gold catalysis via ligand-facilitated enantioselective trapping of reactive intermediates.
Project description:Herein, we report the integration of simple linear regressions with gold(I) catalysis to interrogate the influence of phosphine structure on metal-catalyzed organic transformations. We demonstrate that observed product ratios in [4 + 3]/[4 + 2] cycloisomerization processes are influenced by both steric and electronic properties of the phosphine, which can be represented by the Au-Cl distance. In contrast, the observed selectivity of a similar [2 + 3]/[2 + 2] cycloisomerization is governed by L/B1, a steric parameter. Using this correlation, we were able to accurately predict the selectivity of a previously untested, Buchwald-type ligand to enhance selectivity for the same transformation. This ligand found further utility in increasing the selectivity of a previously reported gold-catalyzed cycloisomerization/arylation of 1,6-enynes by ~1 kcal/mol.
Project description:By employing a chiral bifunctional phosphine ligand, a gold(I)-catalyzed efficient and highly enantioselective dearomatization of phenols is achieved via versatile metal-ligand cooperation. The reaction is proven to be remarkably general in scope, permitting substitutions at all four remaining benzene positions, accommodating electron-withdrawing groups including strongly deactivating nitro, and allowing carbon-based groups of varying steric bulk including tert-butyl at the alkyne terminus. Moreover, besides N-(o-hydroxyphenyl)alkynamides, the corresponding ynoates and ynones are all suitable substrates. Spirocyclohexadienone-pyrrol-2-ones, spirocyclohexadienone-butenolides, and spirocyclohexadenone-cyclopentenones are formed in yields up to 99 % and with ee up to 99 %.
Project description:Densely functionalized alkylidene indanes and indanones can be prepared efficiently in one pot, in high yields with good stereoselectivities (in some cases exclusively the Z-isomer), through a route involving phosphine-catalyzed Michael addition followed by palladium-catalyzed Heck cyclization. These transformations tolerate substrates bearing various substituents around the indane/indanone motif. Employing this technology, a concise formal synthesis of sulindac, a nonsteroidal anti-inflammatory drug, has been established.
Project description:Gold-catalyzed cyclization of 1,5-diynes with ketones as reagents and solvent provides diversely substituted vinyl ethers under mild conditions. The regioselectivity of such gold-catalyzed cyclizations is usually controlled by the scaffold of the diyne. Herein, we report the first solvent-controlled switching of regioselectivity from a 6-endo-dig- to 5-endo-dig-cyclization in these transformations, providing fulvene derivatives. With respect to the functional-group tolerance, aryl fluorides, chlorides, bromides, and ethers are tolerated. Furthermore, the mechanism and selectivity are put to scrutiny by experimental studies and a thermodynamic analysis of the product. Additionally, 6-(vinyloxy)fulvenes are a hitherto unknown class of compounds. Their reactivity is briefly evaluated, to give insights into their potential applications.
Project description:Axially chiral mono(NHC)-Pd(II) and mono(NHC)-Au(I) complexes with one side shaped 1,1'-biphenyl backbone have been prepared from chiral 6,6'-dimethoxybiphenyl-2,2'-diamine. The complexes were characterized by X-ray crystal structure diffraction. The Pd(II) complex showed good catalytic activities in the Suzuki-Miyaura and Heck-Mizoroki coupling reactions, and the (S)-Au(I) complexes also showed good catalytic activities in the asymmetric intramolecular hydroamination reaction to give the corresponding product in moderate ee.