King Kuok (Mimi) Hii

Air- and moisture-stable cationic (diphosphine)palladium(II) complexes as hydroamination catalysts: X-ray crystal structures of two [(diphosphine)Pd(NCMe)(OH2)]2+[OTf]−2 complexes

A series of cationic (diphosphine)palladium(II) complexes have been prepared and fully characterized, including two crystal structures. These complexes were evaluated as catalysts for the hydroamination of acyclic alkenes. The reactivity of the catalysts is dependent on the nature of the diphosphine ligand and the substituents on the amine and alkene substrates.

Delineating Origins of Stereocontrol in Asymmetric Pd-Catalyzed α-Hydroxylation of 1,3-Ketoesters

Systematic studies of reaction conditions and subsequent optimization led to the identification of important parameters for stereoselectivity in the asymmetric alpha-hydroxylation reaction of 1,3-ketoesters. Enantioselectivities of up to 98% can be achieved for cyclic substrates and 88% for acyclic ketoesters. Subsequently, the combination of cyclic/acyclic ketoester, catalyst, and oxidant was found to have a profound effect on reaction rates and turnover-limiting steps. The stereochemistry of the reaction contradicts that observed for other similar electrophilic substitution reactions. This was rationalized by transition-state modeling, which revealed a number of cooperative weak interactions between oxidant, ligand, and counterion, together with C-H/pi interactions that cumulatively account for the unusual stereoselectivity.

Speciation of Pd(OAc)2 in ligandless Suzuki–Miyaura reactions

Generation of catalytically active Pd(0) species from Pd(OAc)2 has been examined, in the context of Suzuki–Miyaura reactions involving substitution of aryl bromides under aerobic and ambient conditions. Using a combination of spectroscopic, microscopic and kinetic measurements, the role of each reaction component is delineated in the speciation of the palladium species. Among the key findings are the effects of O2, H2O and inorganic base, and implications for catalytic activity.

Catalysis in flow: the practical and selective aerobic oxidation of alcohols to aldehydes and ketones

A safe, practical and selective process for the aerobic oxidation of alcohols to aldehydes and ketones has been developed using an Ru catalyst in a continuous flow reactor. Benzylic and allylic alcohols are oxidised selectively to their corresponding aldehydes and ketones, including substrates containing N- and S-heteroatoms. The rate of turnover is compatible with that previously reported using batch or microchannel reactors under optimised conditions. A preliminary kinetic model is derived that is supported by experimental observations. Last but not least, tandem oxidation–olefination may be achieved without the need to isolate the alcohol intermediate or to switch solvent.

Development of palladium catalysts for asymmetric hydroamination reactions

Our development of dicationic palladium(II) complexes for asymmetric hydroamination reactions, particularly the aza-Michael addition, is reviewed.

Examination of Ligand Effects in the Heck Arylation Reaction

Abstract The Heck arylation reaction between aryl bromide and iodide with methyl acrylate was evaluated. A new class of ligands, R–N(CH2CH2PPh2)2, is compared with conventional monodentate and bidentate ligands, and was found to confer greater catalyst stability. The nitrogen substituent (R) has a noticeable effect on the rate of the turnover. We believe this is the first report of the application of such hemilabile ligands in Heck arylation chemistry.

The Heck olefination reaction; A DFT study of the elimination pathway

Abstract Theoretical studies of the pathway in the Heck reaction between ethene and a methyl electrophile at [Pd(H2ACH2AH2)(CH3)(H2CCH2)]+ (A = P, N) reveal intermediates with an agostic H which is the one preferentially transferred to base.

Catalysis in flow: Au-catalysed alkylation of amines by alcohols

By using a greater reaction space afforded by a flow reactor, commercially available Au/TiO2 can be used for highly selective direct alkylation of amines by alcohols, without the need for an inert atmosphere or base. A brief survey of substrates includes the alkylation of aromatic, aliphatic and chiral amines by a number of primary and secondary alcohols, in high yield and selectivity. The synthesis of Piribedil, a drug used in the treatment of Parkinsons disease, can be achieved in a single synthetic operation without the need for column chromatography. Mechanistic aspects of the reaction were revealed through modelling of reaction profiles, and the origin of selectivity is attributed to the accessibility of high temperature. The presence of water was found to be crucial for catalyst activity.

The Intermolecular Asymmetric Heck Reaction: Mechanistic and Computational Studies

Reactive intermediates in the asymmetric Heck reaction between aryl electrophiles and 2,3-dihydrofuran have been identified by NMR and mass spectrometry, with BINAP or the achiral diphosphanes dppp and dppf as ligands. The major cationic species observed is an alkylpalladium produced by addition of PdAr to the alkene followed by two further PdH-mediated isomerisation steps. This last species has been characterised at −60° by 1H-, 13C-, and 31P-NMR, including HMQC techniques. The regiochemistry of PdAr and PdH addition to the reactant are opposite as defined by the reaction with (2-2H1)-2,3-dihydrofuran. DFT Calculations on the reaction pathway between [CH2(PH2)]PdPh+ and 2,3-dihydrofuran reveal several structurally interesting intermediates involving agostic β-H-atom, ipso-Ph or reactant O-atom bonded to the Pd-atom, and elucidate the isomerisation pathway.

Silver‐Catalysed Enantioselective Addition of OH and NH Bonds to Allenes: A New Model for Stereoselectivity Based on Noncovalent Interactions

The ability of silver complexes to catalyse the enantioselective addition of O-H and N-H bonds to allenes is demonstrated for the first time by using optically active anionic ligands that were derived from oxophosphorus(V) acids as the sources of chirality. The intramolecular addition of acids, alcohols, and amines to allenes can be achieved with up to 73% ee. The exploitation of a C-H anomeric effect allowed the absolute configuration of a sample of 2-substituted tetrahydrofuran of low ee to be unambiguously assigned by comparison of the chiroptical ORD and VCD measurements with calculated spectra. In the second part of the work, the origin of the stereoselectivity was probed by DFT free-energy calculations of the transition states. A new model of enantiomeric differentiation was developed that was based on noncovalent interactions. This model allowed us to identify the source of stereoselectivity as weak attractive interactions; such dispersive forces are often overlooked in asymmetric catalysis. A new computational approach was developed that represents these interactions as colour-coded isosurfaces that are characterised by the reduced density-gradient profile.