Asymmetric ligand transformation reactions

Ph.DDOCTOR OF PHILOSOPH

Chiral cyclopalladated complex promoted asymmetric synthesis of diester-substituted P,N-ligands via stepwise hydrophosphination and hydroamination reactions

A series of enantiomerically pure 1,2-diester substituted P,N-ligands incorporating two chiral carbons in the backbone were generated in high yields and high stereoselectivity from acetylenedicarboxylate via initial hydrophosphination using diphenylphosphine followed by hydroamination with various primary and secondary amines. The reactions were activated and stereochemically controlled by the organopalladium complex containing ortho-palladated (S)-(1-(dimethylamino)ethyl)naphthalene under mild conditions. The absolute stereochemistry and the coordination chemistry of P,N-products were determined by the single crystal X-ray diffraction analysis. All the chiral P,N-ligands could be liberated from the palladium template without loss of optical purity. Subsequent recomplexation to selected chiral palladium centers confirmed the optical purity of the new functionalized chiral P,N-ligands

Pd-catalyzed enantiodivergent and regiospecific phospha-michael addition of diphenylphosphine to 4-oxo-enamides : efficient access to chiral phosphinocarboxamides and their analogues

The palladacycle-catalyzed asymmetric P-H addition of 4-oxo-enamides has been developed, which provides efficient access to phosphinocarboxamides and their analogues. Solvent-mediated reversal of stereoselectivity (ee from +96 % to −92 %) was observed, and the underlying mechanism that allows facile access to both enantiomers of the product by judicious choice of solvents is revealed

Air-stable phosphine organocatalysts for the hydroarsination reaction

Readily-available triarylphosphines are explored as organocatalysts for the hydroarsination reaction. When compared to transition metal catalysis, phosphine organocatalysis greatly improved solvent compatibility of the hydroarsination of nitrostyrenes. Upon complete conversion, arsine products were isolated in up to 99% yield while up to 48% of the phosphine catalyst was still active. A mechanism was proposed and structure-activity analysis regarding catalyst activity concluded that sterically-bulkier catalysts were effective at minimizing catalyst deactivation.Nanyang Technological UniversityW. S. T. acknowledges NTU for the award of a research scholarship. This work was supported by the Nanyang Technological University [M401110000 RG 10/19]

Synthesis of stereoprojecting, chiral N-C(sp3)-E type pincer complexes

A synthetic strategy to generate chiral N-C(sp3)-E (E = S, O) pincer complexes incorporating enhanced stereoprojecting groups at the N-arm site has been established. The synthesis of the tridentate pincer ligand was carried out via palladacycle-catalyzed asymmetric hydrophosphination of N-chelating enones. The chelation properties of the substrates were initially demonstrated on C(sp2)-N type palladacycles. The extended substrate scope allows versatile structural modifications on the ligand backbone. Subsequent cyclometalation provided N-C(sp3)-E complexes in a diastereoselective reaction.MOE (Min. of Education, S’pore

Catalytic asymmetric synthesis of Pt- and Pd-PCP pincer complexes bearing a para-N pyridinyl backbone

A diastereoselective catalytic asymmetric hydrophosphination reaction was performed using a palladacycle catalyst to produce chiral PCP phosphine ligand with high dr (95:5) and excellent enantioselectivity (>99% ee). Subsequent facile metalation of the chiral ligand with Pt and Pd metal salts yielded the desired pincer complexes. The protonated form of these pincer complexes was also synthesised, and their structures were confirmed through the use of X-ray crystal diffraction and NMR spectroscopy analyses.MOE (Min. of Education, S’pore

Triflic-acid-catalyzed tandem allylic substitution–cyclization reaction of alcohols with thiophenols—facile access to polysubstituted thiochromans

Hitherto inaccessible multisubstituted thiochroman derivatives were constructed via the one-pot reaction of thiophenols with allylic alcohols catalyzed by 0.2 equiv triflic acid under metal-free conditions. A variety of thiochroman derivatives can be obtained by this straightforward protocol that allows the introduction of up to four substituents at various locations on the thiochroman skeleton. Relative conformations of all isolated products were confirmed by NOESY NMR studies, and a stepwise mechanism, proceeding via an allylic substitution-intramolecular cyclization protocol, is proposed on the basis of NMR experiments.Published versio

Unsymmetrical β-diketiminate magnesium(i) complexes : syntheses and application in catalytic hydroboration of alkyne, nitrile and carbonyl compounds

A series of unsymmetrical β-diketimine coordinated magnesium(i) complexes have been successfully synthesized via reductions of related magnesium(ii) halide complexes with a sodium reducing reagent in toluene or n-hexane solution. All the unsymmetrical magnesium(i) complexes prepared have been crystallographically and spectroscopically characterized. It was found, for the first time, that these well-defined unsymmetrical magnesium(i) complexes were highly active pre-catalysts for the hydroboration of alkynes, nitriles, aldehydes and ketones

Catalytic access to ferrocenyl phosphines bearing both planar and central chirality – A kinetic resolution approach via catalytic asymmetric P(III)–C bond formation

A series of enantioenriched ferrocenyl monophosphines imbued with both central and planar chirality were obtained catalytically (80–99% ee) via the kinetic resolution of 1,2-disubstituted planar chiral ferrocenyl enone racemates. The synthetic approach utilized a chiral palladacycle to facilitate the asymmetric hydrophosphination (AHP) as a means to achieve high stereoselectivity. The enantioenriched ferrocenylphosphine products could be protected and further recrystallized to obtain ees up to 99%. The modularity of the phosphine framework obtained was demonstrated via derivatization of its functional handles via a simple nucleophilic substitution to yield optically pure bisphosphines.Ministry of Education (MOE)This research project is supported by Ministry of Education, Singapore under its AcRF Tier I grant 2017-T1-001-175-02

Inducing thermoreversible optical transitions in urethane-acrylate systems via ionic liquid incorporation for stretchable smart devices

Hydrogels are able to exhibit optical transitions in the presence of external stimuli such as temperature, driven by the lower critical solution temperature (LCST) phenomena. However, they suffer from inherent thermal instability, requiring reswelling for repeated utilisation. Ionogels possess greater thermal stability over conventional hydrogels. However, thermally driven optical transitions via LCST phenomena in ionic liquid incorporated polymer networks have not been studied in-depth. In this work, we incorporated a low amount of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide in a polymer matrix, to trigger the desired reversible optical transitions based on the LCST phenomenon. The composition of the ionic liquid elastomer hybrid is in contrast to conventional hydrogels which possess high amounts of liquid. We present NMR and UV-Vis spectroscopic studies to reveal the underlying reversible hydrogen bonding based mechanism behind this optical transition. Unlike conventional hydrogels, our hybrids show excellent thermal and ambient stability along with repeatable optical transitions with comparable response time, indicative of their long term use in harsher environments. Improvements in the mechanical properties with the inclusion of ionic liquid in our hybrids were also observed (40% increase in ultimate strain, 34% decrease in Young’s modulus). The enhanced properties and optical transition of the ionic liquid elastomer hybrids allowed them to serve as a patternable smart display and a stretchable & flexible device.Ministry of Education (MOE)Nanyang Technological UniversityAccepted versionAuthors would like to acknowledge funding support for this work from the CN Yang Scholars Program and Ministry of Education (MOE) Tier 1 grant (MOE2018-T1-002-179) (Singapore)