Synthetic Organic Chemistry

Past Projects

Our group is generally interested in developing new catalytic reactions that is also environmentally responsible. During the last decade, spectacular advances have been made in catalytic methods using small organic molecules. Our group contributed to this area by demonstrating the use of chiral guanidines as general Brønsted base catalysts. We have also demonstrated the use of simple, cheap, commercially available organic dyes as photocatalysts.

Collaborators

Prof. Richard Wong Ming Wah (NUS)

Prof. Hajime Hirao (CityU, Hong Kong)

Prof. Kuo-Wei Huang (KAUST)

Dr. Richmond Lee (University of Wollongong)

Dr. Kee Choon Wee (NTU, ICES A*STAR)

Phase Transfer Catalysis

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Phase-transfer catalysis (PTC) is known to increase yields, reduce cycle times, eliminates hazardous/expensive reagents and reduces solvents use. It is also simple to perform and has high possibility to conduct large-scale preparations in industrial processes. The first successful industrial application was demonstrated in 1984, by Merck using a Cinchonidium as catalyst in the chiral phase transfer methylation reaction. The latest and most exciting revolution in chiral phase transfer catalysis came when Maruoka reported the quaternary ammonium catalysts, which can be applied in a wide range of reactions. We have developed a new class of PTC catalyst and coined them the pentanidiums, as these are new chemical entities unknown to literature. These catalysts are easy to prepare and in short number of steps. It is also amenable to a wide scope of modifications and could potentially be used for a significant range of mild reactions. We are also keen to develop new concepts in PTC reactions.

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Selected Publications:

  • L. Zong, X. Ban, C.W. Kee, C.-H. Tan, Catalytic Enantioselective Alkylation of Sulfenate Anions to Chiral Heterocyclic Sulfoxides Using Halogenated Pentanidiums, Angewandte Chemie International Edition, 2014, 53, 11849 – 11853.

  • Y. Yang, F. Moinodeen, W. Chin, T. Ma, Z. Jiang, C.-H. Tan, Phase Transfer Pentanidium-Catalyzed Enantioselective α-Hydroxylation of Oxindole with Molecular Oxygen, Organic Letters, 2012, 14, 4762–4765.

  • T. Ma, X. Fu, C. W. Kee, L. Zong, Y. Pan, K.-W. Huang, C.-H. Tan, Pentanidium catalyzed enantioselective phase transfer conjugate addition reactions, Journal of the American Chemical Society, 2011, 133, 2828–2831.

Halogen Bonding in Catalysis

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Halogen bonding (XB) is a non-covalent interaction between a halogen atom (X) acting as a Lewis acid and an electron donor acting as Lewis base. This non-covalent interaction has impacted research fields that require control of intermolecular recognition and self-assembly processes. In particular, it has found applications in crystal engineering and supramolecular chemistry. We recently reported halogen-bonding-induced hydrogen transfer to C=N bond with Hantzsch Ester using bidentate dihydroimidazolines as catalysts.

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Selected Publications:

  • X. Zhang, J. Ren, S. M. Tan, D. Tan, R. Lee, C.-H. Tan, Enantioconvergent Halogenophilic Nucleophilic Substitution (SN2X) Reaction, Science, 2019, 363, 400 404.

  • L. Zong, S. Du, K. F. Chin, C. Wang, C.-H. Tan, Enantioselective Synthesis of Quaternary Carbon Stereocenters: Addition of 3-Substituted Oxindoles to Vinyl Sulfone Catalysed with Pentanidiums, Angewandte Chemie International Edition, 2015, 54, 9390 9393. 

  • W. He, Y. Ge, C.-H. Tan, Halogen-Bonding-Induced Hydrogen Transfer to C=N Bond with Hantzsch Ester, Organic Letters, 2014, 16, 3244 – 3247.

  • X. Zhang and C.-H. Tan, SN2 and SN2X Reactions at Tertiary Carbon Centers, Chem, 2021, 7, 1451–1486. 

Ion Pair Catalysis

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Phase transfer reactions using chiral cations and inorganic basic salts such as hydroxides and carbonates are but a sub-set of a larger group of reactions known as chiral cation ion-pairing catalysis. We report two reactions using chiral dicationic bisguanidinium ion-pair catalysts; they are each paired with two different organometallic anions – permanganate and tungstate. The ion pairs-catalyzed asymmetric oxidation reaction of alkenes and sulfoxidation respectively. In this new mode of catalysis, evidence suggests that rate acceleration is mainly attributed to transition state stabilization through attractive cation-anion interaction rather than enhancing solubility in organic solvents.

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Selected Publications:

  • L. Zong, C. Wang, X. Ye, C.-H. Tan, Bisguanidinium Dinuclear Oxodiperoxomolybdosulfate [(μ2-SO4)Mo2O2(μ2-O2)2(O2)2]  Ion-Pair: Characterization and Application in Asymmetric Sulfoxidation,  Nature Communications, 2016, 7, 13455.

  • L. Zong, C.-H Tan, Phase Transfer and Ion Pairing Catalysis of Pentanidiums and Bisguanidiniums, Accounts of Chemical Research, 2017, 50, 842 856.

  • X. Ye, A. M. P. Moeljadi, K. F. Chin, H. Hirao, L. Zong, C.-H. Tan, Bisguanidinium Diphosphatobisperoxotungstate Ion-pair Catalyzed Enantioselective Sulfoxidation, Angewandte Chemie International Edition, 2016, 55, 7101 – 7105

  • C. Wang, L. Zong, C.-H. Tan, Enantioselective Oxidation of Alkenes with Potassium Permanganate Catalyzed by Chiral Dicationic Bisguanidinium, , Journal of the American Chemical Society, 2015, 137, 10677 – 10682 (Highlighted by ACS Select Virtual Issue on Organocatalysis).

  • X. Ye and C.-H. Tan, Enantioselective Ion-Pair Catalysis Directed by Chiral Cation and Transition Metal, Chemical Science, 2021, 12, 533 539. 

Robot-Assisted Organic Synthesis

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DENSO Robotic arm performed a chemical reaction and analysed the sample on GCMS autonomously. 

Link to video: https://www.youtube.com/watch?v=mkXN7RIrHY0

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Brønsted Base Catalysed Reactions

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Chiral guanidines have been developed as an important type of organocatalyst in numerous asymmetric reactions. We have developed bicyclic-guanidines and guanidiniums as catalysts for a wide range of reactions such as Diels-Alder reaction, protonation, Mannich reaction, decarboxylative reaction, Michael reaction and amination reaction.

Selected Publications:

  • H. Liu, D. Leow, C.-H. Tan, Enantioselective synthesis of chiral allenes by guanidine-catalyzed isomerization of alkynes, Journal of the American Chemical Society, 2009, 131, 7212–7213.

  • D. Leow and C.-H. Tan, Chiral guanidines catalyzed enantioselective reactions, Chemistry - An Asian Journal, 2009, 4, 488–507.

  • D. Leow, S. Lin, S. K. Chittimalla, X. Fu and C.-H. Tan, Enantioselective protonations catalyzed by chiral bicyclic guanidine, Angewandte Chemie International Edition English, 2008, 47, 5641–5645.

  • J. Shen, T. T. Nguyen, Y.-P. Goh, W. Ye, X. Fu, J. Xu and C.-H. Tan, Chiral bicyclic guanidine catalyzed enantioselective reactions of anthrones. Journal of the American Chemical Society, 2006, 128, 13692–13693.

Organic Dye Catalysed Photoreactions

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We have showed that Rose Bengal, an organic dye, can be used as a visible light photocatalyst for several reactions including α-oxyamination reactions between 1,3-dicarbonyl compounds and TEMPO and cross-dehydrogenative reactions.

Selected Publications:

  • C. W. Kee, C.-H. Tan, Organic Dye Photoredox Catalyzed C-H Bromination Reaction Using Visible Light, Asian Journal of Organic Chemistry, 2014, 3, 536 – 544.

  • Y. Pan, S. Wang, C. W. Kee, E. Dubuisson, K. P. Loh, and C.-H. Tan, Rose Bengal and Graphene Oxide: Oxidative C-H functionalization of tertiary amines using visible Light, Green Chemistry, 2011, 13, 3341–3344.

  • Y. Pan, C. W. Kee, L. Chen and C.-H. Tan, Dehydrogenative coupling reactions catalyzed by Rose Bengal using visible light irradiation, Green Chemistry, 2011, 13, 2682–2685.

  • H. Liu, W. Feng, Y. Zhao, D. Leow, Y. Pan, C.-H. Tan, Organic dye photocatalyzed α-oxyamination through irradiation with visible light, Green Chemistry, 2010, 12, 953 – 956

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Others

Our laboratory also conducted preliminary studies on methodology using nucleophilic bases, environmentally benign catalytic systems using molecular oxygen, biomimetic reactions using enzyme cofactor (flavins as catalyst) and iodobenzene-catalyzed reactions.

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