Design, Synthesis, and Stereochemical Evaluation of a Novel Chiral Amine-Palladacycle

A novel chiral palladacycle was designed and synthesized via a multi-step synthesis. The racemic cyclopalladated complex could be efficiently resolved via the formation of its (S)-prolinato and (S)-alaninato derivatives. With the new palladacycle used as the chiral template, the stereoselectivity of Diels–Alder cycloaddition between DMPP and ethyl vinyl ketone was found to be significantly improved compared with other analogue complexes

Yi Ding, Yongxin Li, Yi Zhang, Sumod A. Pullarkat, Pak-Hing Leung*, Eur. J. Inorg. Chem., article online in advance of print. doi:10.1002/ejic.200701234

Base controlled (1,1)- and (1,2)-hydrophosphination of functionalized alkyne

The (1,1)- and (1,2)-addition of diphenylphosphine to 3-bulyn-2-one and ethyl propiolate could be controlled chemoselectively by regulating the amount of triethylamine as the external base and in the presence of the chiral organopalladium(II) template derived from (R)-N,N-dimethyl-1-(1-naphthyl)ethylamine.

Yi Zhang, Lulu Tang, Yi Ding, Jia-Hui Chua, Yongxin Li, Mingjun Yuan and Pak-Hing Leung, Tetrahedron Letters, Volume 49, Issue 11, 10 March 2008,Pages 1762-1767

Novel Stereochemistry, Reactivity and Stability of an Arsenic Heterocycle in Metal Promoted Asymmetric Cycloaddition Reaction

Stereoselectivity and reactivity of cyclic arsines have been much less studied compared to phospholes. In order to enrich this hetero-bidentate chemistry, we have decided to explore the chemistry of arsoles. We herein report the metal promoted cycloaddition reaction of 3, 4-dimethyl-1-phenylarsole and the stability of the resulting novel arsanorbornene. A chiral phosphine-olefin hybrid palladium complex was obtained as a consequence of a novel arsine elimination process.

Mengtao Ma, Sumod A. Pullarkat, Yongxin Li, and Pak-Hing Leung., Inorg. Chem., 46(22), 9488-9494, 2007.

Wave packet theory of dynamic stimulated Raman spectra in femtosecond
pump-probe spectroscopy

The quantum theory for stimulated Raman spectroscopy from a moving third-order density matrix and polarization is derived....

Zhigang Sun, Zhongqi Jin, J. Lu, Dong H. Zhang, Soo-Y. Lee, The Journal Of Chemical Physics 126, 174104 (2007)

Seven-dimensional quantum dynamics study of the O(³P) +CH₄ reaction

The initial state selected time-dependent wave packet calculations have been carried out to study the title reaction with seven...

Minghui Yang, Soo-Y. Lee, Dong H. Zhang, The Journal Of Chemical Physics 126, 064303 (2007)

Conformational Analyses of the Five-membered Palladacycles Derived from 1-(1'-Naphthyl) ethyldiphenylphosphine and its Arsenic Analogue

As part of our continued interest in developing novel chiral templates, we have previously reported on the development of the analogous diphenylphosphino- and diphenylarsino based palladacycles in the optically active forms. In designing chiral Lewis acids for future use as catalysts or auxiliaries for asymmetric transformations, the necessity to first assess the stereochemical behaviors of these systems is significant and cannot be undermined. This article is aimed at providing the results of the studies of the conformational characteristics of our newly developed five membered palladacycle systems, in both solid state and in solution.

Joseph Kok-Peng Ng, Shuli Chen, Pak-Hing Leung et. al., Tetrahedron: Asymmetry, 2007, 18(10), 1163-1169.

The Oxidative Electrochemistry of Vitamin E

A combination of electrochemical and spectroscopic experiments have proven that the α, β, γ and δ-forms (vitamers) of the tocopherols (vitamin E) undergo a series of chemically reversible proton and electron transfer steps to form cationic compounds; the cation radical, the dication and the phenoxonium cation. The cationic compounds are extremely unusual in their high persistence compared to what is presently known about the oxidative stability of other phenols, particularly the phenoxonium cation of a-tocopherol which is stable for at least several hours in non-aqueous solvents and may have important biological properties.

Webster, R. D. New Insights Into The Oxidative Electrochemistry of Vitamin E. Acc. Chem. Res. 2007, 40, 251–257.

Substituent Effects on the Stereoelectronic and Chemical Properties of a Novel Phosphapalladacycle.

The works reported herein serves to describe the development and characteristics of a new phosphorus-based palladacycle that was prepared in the optically active state.

Joseph Kok-Peng Ng, Shuli Chen, Pak-Hing Leung et. al., European Journal of Inorganic Chemistry, 2007, 3124-3134.

Synthesis of P-Chiral Phosphines via Chiral Metal Template Promoted Asymmetric Furan Diels-Alder Reaction

The asymmetric cycloaddition reaction between phenyldivinylphosphine and 2-diphenylphosphinofuran, was achieved in a highly stereoselective manner.

Wee-Chuan Yeo , Shuli Chen Pak-Hing Leung et. al,. Journal of Organometallic Chemistry, 2007, 692(12), 2539-2547.

Cyclopalladation of the Prochiral (Di-tert-butyl) (diphenylmethyl) phosphine: Kinetic Lability of the Corresponding (+)-Phosphapalladacyclic Pd – C Bond and the Reluctance of the Phosphine to Bind in a Monodentate Fashion

Considering the very promising roles of phosphapalladacycles as catalysts,the development new variants of these unique class of organopalladium complexes is critical.
This paper describes the preparation of a novel phosphapalladacycle in the optically active form and discusses the kinetic lability of the Pd – C bond from optical rotation data.

Joseph Kok-Peng Ng, Shuli Chen, Yongxin Li, Pak-Hing Leung et.al., Inorganic Chemistry, 2007, 46(12), 5100-5109.

A Novel Asymmetric Hydroarsination Reaction Promoted by Chiral Organo-Palladium Complex

The dissymmetrical chiral bidentate (R)-(+)-1-diphenylphosphino-2-diphenylarsinopropane was prepared stereoselectively via the novel asymmetric hydroarsination reaction between diphenylarsine and diphenyl-1-propenyl-(E)-phosphine employing a chiral promoter.

Maricar L. Bungabong, Kien Wee Tan, Yongxin Li, Selvasothi V. Selvaratnam, Krishna G. Dongol, Pak-Hing Leung, Inorganic Chemistry, 2007, 46(11), 4733-4736.

Asymmetric synthesis of dimethyl-1, 2-bis-(diphenylphosphino)-1, 2-ethanedicarboxylate by means of a chiral palladium template promoted hydrophosphination reaction

The optically pure (+)-As-P heterobidentate cycloadduct was synthesized stereospecifically by utilizing an organoplatinum reaction promoter containing the ortho-metalated (R)-(1-(dimethylamino)ethyl)-naphthalene as the chiral auxiliary.

Tang Lulu, Zhang Yi, Ding Luo, Leung Pak-Hing et al., Tetrahedron Letters., 48 (1): 33-35, 2007

Functionalization of Metal-Protected Chiral Phosphines via Simple Organic Transformations

With metal as protection, the introduction of functionalities on coordinated chiral phosphines using organic transformations is achieved thus yielding an effective
methodology for the synthesis of functionalized chiral phosphine molecules.

Wee-Chuan Yeo, Pak-Hing Leung et. al., Organometallics, 25 (5), 1259 -1269, 2006

A Novel Approach towards Asymmetric Synthesis of Alcohol Functionalized C-Chiral Diphosphines via two Stage Hydrophosphination of Terminal Alkynols

Alcohol functionalized diphosphine ligands with chirality residing on the carbon backbone has been prepared using a novel two stage asymmetric synthetic methodology from the corresponding terminal alkynols.

Sumod A. Pullarkat, Ding Yi, Yongxin Li, Pak-Hing Leung et. al., Inorganic Chemistry, 45 (18): 7455-7463, 2006

Asymmetric synthesis of a P-chiral heteroditopic P^P=S ligand via chiral metal template promoted cycloaddition between 3, 4- Dimethyl-1-phenylphosphole and its sulfonated analog

The asymmetric [4+2] Diels-Alder reaction involving 3,4-dimethyl-1-phenylphosphole, DMPP, as the cyclic diene and its P-sulfonated analogue DMPP=S as the dienophile was carried out by utilizing the palladium(II) template complex containing ortho-metalated (R)-(1-(dimethylamino)ethyl)naphthalene as the chiral auxiliary.

Sumod A.Pullarkat, Ma Mengtao, Leung Pak-Hing et. al. J. Organomet. Chem, 691 (13): 3083-3088, 2006

Asymmetric synthesis of a chiral arsinophosphine via a metal template promoted asymmetric Diels-Alder reaction between diphenylvinylphosphine and 2-furyldiphenylarsine

The cycloaddition reaction between 2-furyl-diphenylarsine and diphenylvinylphosphine was achieved stereospecifically by utilizing an organoplatinum complex as reaction promoter and chiral auxiliary.

Tan Kien Wee, Liu Feng Li , Li Yongxin, Leung Pak-Hing et al. Journal of Organometallic Chemistry, 691 (22): 4753-4758, 2006

Polyene Cyclizations

Interesting asymmetric Lewis acid-mediated intermolecular acetal-initialed cationic polyene cyclization to form tricyclic compounds is reported in this paper.

Yu-Jun Zhao, Shu-Sin Chng and Teck-Peng Loh. J. Am. Chem. Soc. 2007, 129, 492 – 493.

Enantioselective Michael Addition Reaction

A highly regio- and enantio-selective Cu(I) Tol-BINAP-catalyzed Michael reaction of Grignard reagents and unsaturated esters has been reported.

Shun-Yi Wang, Shun-Jun Ji and Teck-Peng Loh. J. Am. Chem. Soc. 2007, 129, 276 – 277.

Formal Synthesis of (+)-SCH 351448

(+) SCH 351448 is the first small molecule activator of the low density lipoprotein receptor (LDL-R) promoter identified. A formal synthesis of (+)SCH 351448 has been successfully accomplished via the Prins cyclization approach.

Kok-Ping Chan, Yvonne Hui Ling and Teck-Peng Loh Chem. Commun. 2007, 939 – 941.

Diastereoselective Allylation of Planar Chiral Substituted Ferrocenecarboxaldehyde

An efficient entry to chiral ferrocenyl ligands.

Hao Li, Hin-Soon Cheng, Ai-Hua Seow and Teck-Peng Loh Tetrahedron Lett. 2007, 48, 2209 – 2211.

Chemoselective Hydrodehalodenation

A stannane-free hydrodehalogenation of 4-halotetrahydropyran which allows selective one-pot dehalogenation and/or benzylation.

Kok-Ping Chan, Yvonne Hui Ling, Jocelyn Li-Ting Chan and Teck-Peng Loh J. Org. Chem. 2007,in press.

Stereochemical Prins Cyclization: Electronic vs Steric Effects

A convenient approach towards the synthesis of both syn- and anti-2,4,6-chlorotetra-hydropyrans. The electronic and steric influences on the stereochmemistry of the Prins cyclized products were investigated.

Kok-Ping Chan, Ai-Hua Seow and Teck-Peng Loh Tetrahedron Lett. 2007, 48, 37 – 41.

Catalytic Enantioselective Diels-Alder Reaction in Ionic Liquid via a Recyclable Chiral In(III) Complex

A recyclable, air- and moisture-stable chiral indium complex in ionic liquid has been developed. The cycloaddition of a variety of cyclic and open-chained dienes to 2-methacrolein and 2-bromoacrolein resulted in good yields and excellent enantioselectivities (up to 98% ee).

Fan Fu, Yong-Chua Teo and Teck-Peng Loh Org. Lett. 2006, 8, 5999 – 6001.

Novel Design of Water-Tolerant Lewis Acid

A novel chiral indium(III) camphorsulfonate complex was developed as a water-tolerant Lewis acid to afford high yields (up to 99%) in one-pot three component Mannich-type reactions in a true water environment.

Jian Xiao and Teck-Peng Loh. Synlett 2007, 5, 815-817.

A Complete and Precise Review on Indium Complexes

This is a fascinating summary on our decade of excellent work on indium complexes as Lewis acids.

Teck-Peng Loh and Guan-Leong Chua. Chem. Commun. 2006, 2739 – 2749.

Total Synthesis of Antillatoxin

Antillatoxin has been shown to be neurotoxic in primary cultures of rat cerebellar granule cells and also induced a concentration-dependent cytotoxicity in cerebellar granule neurons. The total synthesis of natural (4R,5R)-antillatoxin and its analog (4R,5R)-antillatoxin were completed in very short steps.

Kiew-Ching Lee and Teck-Peng Loh. Chem. Commun. 2006, 4209 – 4211.

First detection of an organometallic Ru(V) compound

Electrochemical methods have been used to synthesis the first Ru(V) organometallic compound, which is stable in solution for at least several hours. This work opens a new route into the preparation of other very high oxidation state ruthenium compounds, which potentially have useful properties as catalysts.

Kuan, S. L.; Tay, E. P. L.; Leong, W. K.; Goh, L. Y.; Lin, C. Y.; Gill, P. M. W.; Webster, R. D. "Highly Oxidized Ruthenium Organometallic Compounds. The Synthesis and One-Electron Electrochemical Oxidation of [Cp*RuIVCl2(S2CR)] (Cp* = ?5-C5Me5, R = NMe2, NEt2, OiPr)." Organometallics, 2006, 25, 6134-6141.

Photochromic Materials Through Microwave Technology

An efficient microwave promoted method for the synthesis of photochromic materials has been developed by Professor Loh's group, providing an easy access to compounds that have applications in eye-care products, security printing, optical data storage etc.

Lee, W.-W. W.; Gan, L.-M.; Loh, T.-P., "Synthesis and photochromic properties of cycloalkylidene fulgides", Synlett, 16, 2473-2477, 2005.

Finally, An Access To Multigram Quantities Of Epibatidine!

750 frogs (Epipedobates tricolor) would only yield 1.3 mg of Epibatidine, a potent natural product with interesting biological activities. This compound is now easily accessible with the accomplishment of its gram-scale synthesis in Prof. Loh's group.

Li, K. C.-L.; Loh, T.-P., "Gram-Scale Synthesis of (-)-Epibatidine", Organic Letters, 2005, 7, 2965-2967.

Novel Chiral Indium Complexes: Potential Applications In Drug Synthesis

Control of chirality in building complex molecules now takes a new development with novel chiral indium complexes developed in Prof Loh's group. These were found to work in ionic liquids, combining synthetic control with green chemistry to yield ultrapure compounds in environmentally friendly media.

Teo, Y.-C.; Goh, E.-L.; Loh, T.-P., "Catalytic enantioselective allylation of aldehydes via a moisture-tolerant chiral BINOL-In(III) complex", Tetrahedron Lett., 2005, 46, 6209-6211.

Teo, Y.-C.; Goh, E.-L.; Loh, T.-P., "Catalytic enantioselective allylation of aldehydes via a chiral indium(III) complex in ionic liquids", Tetrahedron Lett., 2005, 46, 4573-4575.

Teo, Y.-C.; Goh, J. D.; Loh, T.-P., "Catalytic Enantioselective Allylation of Ketones via a chiral Indium(III) complex", Org. Lett., 2005, 7, 2743-2745.

Lu, J.; Ji, S.-J.; Loh, T.-P., "Enantioselective allylation of aldehydes catalyzed by chiral indium (III) complexes immobilized in ionic liquids", Chem. Commun., 2005, 2345-2347.

Teo, Y.-C.; Loh, T.-P., "Catalytic Asymmetric Diels-Alder via a chiral Indium(III) complex", Org. Lett., 2005, 7, 2539-2541.

Selectivity Leakage: A New Concept In Synthesis

Selectivity leakage is a term coined by Prof. Loh for the lost in product handedness in the course of a reaction. With this new concept, careful tuning of the reaction conditions to suppress the leakage of selectivity can be developed and natural products can be made with high enantioselectivies, essential for medicinal potencies.

Chan, K.-P.; Loh, T.-P., "Prins Cyclizations in Silyl Additives with Suppression of Epimerization: Versatile Tool in the Synthesis of the Tetrahydropyran Backbone of Natural Products"; Org. Lett., Vol. 7, No. 20 , 4491-4494, 2005.

Another Step Towards Environmentally Friendly Synthesis Processes

Prof. Loh's group has been developing new environmentally friendly organic reactions since its inception. His work in this area has been highlighted in the 08 Nov '04 issue of Chemical and Engineering News. Recently, a new reaction dispensing with the need for toxic metal complexes has been developed.

Shen, Z.-L.; Ji, S.-J.; Loh, T.-P., "Ionic liquid [Omim][PF6] as an efficient and recyclable reaction media for the cyanosilylation of aldehydes without Lewis acid or special activiation", Tetrahedron Lett., 2005, 46, 3137-3139.

Dependence Of Line Shapes In Femtosecond Broadband Simulated Raman Spectroscopy On Pump-Probe Delay Time

S. Yoon, D.W. McCamant, P. Kukura, R.A. Mathies, D. Zhang and S.Y. Lee, Journal of Chemical Physics, 122, 024505(1-9), 2005.

A Full Dimensional Time-Dependent Wave Packet Study For The H4 Four-Center, Collision Induced Dissociation, And Single Exchange Reactions: Reaction Probabilities For J=0

Y. Lu, S.Y. Lee and D.H. Zhang, Journal of Chemical Physics

Highly Efficient Synthesis Of An Important Class Of Molecules

Molecules having two different atoms attached to a metal centre have proven to be useful in the field of catalysis and medicinal research. Herein we report an efficient method for synthesis of these commercially important compounds through an efficient synthetic protocol using a tailor made metal complex in high purity and yield.

Leung Pak-Hing et. al., "Chiral metal Template Induced Asymmetric Synthesis of a Mixed Phosphine-Phosphine Oxide Ligand", Organometallics, 2005, 24 (23), 5581-5585

Use Of Environmentally Friendly Solvents- A Step Towards "Greener" Chemistry

As chemists try to adopt more environmentally friendly methods for synthesis, the role of "green" solvents have come into focus. Here we report the adoption of an environmentally friendly solvent to carry out a reaction for the synthesis of an important class of phosphorous compound.

Leung Pak-Hing et.al., "Organopalladium complex promoted asymmetric synthesis of a P-chiral phosphanorbornene in ionic liquids and in organic solvents". J. Organomet. Chem., 2005, 690, 4933-4938

Challenges In The Preparation Of "Mirror" Molecules

Chiral molecules are valuable in the fields of catalysis and pharmaceuticals. Obtaining a pure chiral molecule in appreciable excess from a reaction that generates numerous other chiral molecules is a major challenge in synthetic chemistry. Our laboratory has perfected a method for synthesizing chiral molecules in their pure forms in high yield.

Leung Pak-Hing et.al., "Asymmmetric [2+2] cycloaddition of (E)-2-(Diphenylphosphanyl)styrene promoted by a chiral metal template." , Eur. J. Inorg. Chem., 2005, article online in advance of print.

Designing Molecules and Studying Their 2-D Structures

Synthesizing molecules with the desired properties is the closest we can come to playing nature. We have succeeded in making molecules and altering their properties based on the potential uses that we foresee for them. We have also been able to study the 2-D shape of the molecule using advanced instrumentation.

Leung Pak-Hing et.al., "Stereochemical Investigations of a Novel Class of Chiral Phosphapalladacycle Complexes Derived from 1-[(2, 5-dimethyl)phenyl]ethyldiphenylphosphine", Inorg. Chem., 2005, accepted for publication.