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We developed a general procedure for palladium-catalyzed radical alkylation of activated arenes. Electron-deficient benzenes and naphthalene derivatives reacted to give alkylated products in moderate to good yields. The alkyl radicals added to para position of strong electron-withdrawing groups on the arenes. This alkylation method complements with traditional Friedel-Crafts alkylation which reacted well with electron-rich and neutral arenes. We reported asymmetric transfer hydrogenation of 2-substituted quinoxalines using Ni/TangPhos as the catalyst and formic acid as the source of hydrogen. Moderate to good enantioselectivities were obtained depending on the substituents. We also realized a one-pot reductive amination between 1,2-phenylenediamine and substituted glyoxal. The two spontaneously condensed to form quinoxalines. The later was not isolated and subjected to nickel catalyzed asymmetric transfer hydrogenation. We realized a challenging Heck arylation of N-substituted maleimides, which are exceedingly prone to basic hydrolysis. We found a combination of weak base KOAc in ethylene carbonate solvent helped to slow down the ring-opening side reactions of sensitive maleimide to form the Heck product in good yield and with good generality. ​Doctor of Philosophy (SPMS)

Intermolecular alkylations of electron‐deficient arenes proceed with good para selectivity. Palladium catalysts were used to generate nucleophilic alkyl radicals from alkyl halides, which then directly add onto the arenes. The arene scope and the site of alkylation are opposite to those of classical Friedel–Crafts alkylations, which prefer electron‐rich systems. MOE (Min. of Education, S’pore) Accepted version

An asymmetric reductive amination of ketones using both arylamines and benzhydrazide in the presence of nickel catalysts was developed. A one-pot synthesis of tetrahydroquinoxalines was also developed starting directly from α-ketoaldehydes and 1,2-diaminobenzene. Formic acid was used as a safe and economic surrogate for high-pressure hydrogen gas. Strongly σ-donating bis(alkylphosphine)s are crucial ancillary ligands for both stereoselective hydride insertion and decarboxylation of the formate.

The structure and stability of emulsions formed in the presence of nanoparticles of poly(lactic-co-glycolic acid) (PLGA) were characterised. From oil-water contact angles on PLGA films, it was deduced that particle surface hydrophobicity is linked to the oil phase polarity. Incorporation of polyvinyl alcohol molecules into the nanoparticle surfaces reduces the particle hydrophobicity sufficiently for oil-in-water emulsions to be preferentially stabilised. PLGA nanoparticles enhance the stability of emulsions formed from a wide range of oils of different polarities. The nanoparticle concentration was found to be a key parameter controlling the average size and coalescence stability of the emulsion drops. Visualisation of the interfacial structure by electron microscopy indicated that PLGA nanoparticles were located at the drop surfaces, evidence of the capacity of these particles to stabilise Pickering-type emulsions. These results provide insights into the mechanism of PLGA nanoparticle stabilisation of emulsions. Refereed/Peer-reviewed

Maleimides are extremely susceptible to basic hydrolysis and gave poor yields under Heck conditions. The longstanding problem is solved with the use of a weak base KOAc in a carbonate solvent. MOE (Min. of Education, S’pore) Accepted version

This study reports on the physicochemical characterisation and in vitro investigations of macro-porous silica-lipid hybrid (SLH) microcapsules when formulated using various lipids: long-chain triglycerides (LCT), medium-chain triglycerides (MCT), medium-chain mono-, diglycerides (MCMDG); and emulsifiers: anionic lecithin and cationic oleylamine. For the lipophilic compound coumarin 102 (log P = 4.09), a complete and immediate in vitro release was attained for the SLH microcapsules under simulated intestinal sink conditions. The in vitro digestion study of various types of SLH microcapsules demonstrates: (i) reduced variability and enhanced lipid digestibility for the MCMDG-based microcapsules (i.e. 90-100% lipolysis) in comparison with an equivalent lipid solution and emulsion (50-90% lipolysis); and (ii) more controllable digestion kinetics for the LCT-based microcapsules which produce a lipolysis rate higher than that of a lipid solution but lower than that of a lipid emulsion. The drug phase partition results show approximately 5- to 17-fold increase in the drug solubilisation degree resulting from the digestion of MCT and MCMDG-based microcapsules (116 µg/mL), and LCT-based microcapsules (416 µg/mL) in comparison with the blank micellar medium (24 µg/mL). In conclusion, the SLH microcapsules could be tailored to manipulate the digestion patterns of both medium- and long-chain lipids in order to maximise the drug solubilisation capacity. Refereed/Peer-reviewed

The maintenance of appropriate arterial tone is critically important for normal physiological arterial function. However, the cellular and molecular mechanisms remain poorly defined. Here, we have shown that in the mouse aorta, resident macrophages prevented arterial stiffness and collagen deposition in the steady state. Using phenotyping, transcriptional profiling, and targeted deletion of Csf1r, we have demonstrated that these macrophages-which are a feature of blood vessels invested with smooth muscle cells (SMCs) in both mouse and human tissues-expressed the hyaluronan (HA) receptor LYVE-l. Furthermore, we have shown they possessed the unique ability to modulate collagen expression in SMCs by matrix metalloproteinase MMP-9-dependent proteolysis through engagement of LYVE-1 with the HA pericellular matrix of SMCs. Our study has unveiled a hitherto unknown homeostatic contribution of arterial LYVE-1+ macrophages through the control of collagen production by SMCs and has identified a function of LYVE-1 in leukocytes. NRF (Natl Research Foundation, S’pore) NMRC (Natl Medical Research Council, S’pore)

An efficient Heck method for the arylation of maleimides which easily undergo hydrolysis is presented.

A general method for the asymmetric synthesis of various α-arylated lactones using chiral phosphine ligands is developed.

Different enol acetates are treated with aryl and vinyl triflates as well as aryl halides in the presence of chiral phenoxy-substituted ligands (I).

Most existingmethods, however, were limited to formation of quaternarycenters. Coupling to form more common tertiary centersproved to be more difficult, because of fast product race-mization under basic conditions.To address this deficiency, the groups of MacMillan andGaunt independently reported copper-catalyzed arylation ofsilylketenimidesandenaminesformedinsitufromaldehydes.One silyl enolate derived from valerolactone can react withseveral diaryliodonium salts to give about 90% ee (Sche-me 1b).

). However, no product wasformed in the presence of LiOAc. With CsF, arylationoccurred, but the product racemized. To our delight, wefinally found that the tin enolate of 1-tetralone can couplevery efficiently with 91% ee when L1 was used. No erosion ofthe ee value was observed over time. The tin enolate wasformed easily by stirring alkenyl acetate with nBu