Professor LU Yixin
B.Sc., Fudan University, M.Sc., Dalian University of Technology, Ph.D., McGill University, Post doctoral Fellow, Clinical Research Institute of Montreal; Nagoya University
Department of Chemistry, NUS
3 Science Drive 3
ASYMMETRIC CATALYSIS AND SYNTHESIS
Our group has keen interests in asymmetric catalysis/synthesis. Currently, the focus has been placed in developing enantioselective processes that can be promoted by small organic molecules. In particular, we are interested in devising highly efficient and versatile catalytic systems that can be readily derived from the chiral pools, and intend to apply our methodologies for the preparation of biologically important and synthetically useful molecules.
Amino catalysis promoted by primary amino acids/amines
L-Proline and its analogues have been predominantly used in amino catalysis. We initiated a research program in which primary amino acids/amines, rather than the secondary pyrrolidine moiety, were utilized as the catalyst for a range of important asymmetric transformations. We demonstrated that primary amine organic catalysts have often shown to be complementary or superior, in comparison with secondary amine-mediated processes. For instance, we discovered that natural tryptophan and silylated threonine were efficient catalysts for the direct aldol and Mannich reaction in aqueous media, respectively.
Amino acid-derived novel tertiary amine-thiourea bifunctional catalysts
Amino acids are probably the most readily available, most versatile and most economical chiral building blocks available to chemists, therefore, we were intrigued by the possibility of deriving a wide array of novel bi(multi)functional organocatalysts from simple amino acid structural scaffolds. To test our hypothesis, we designed tryptophan-based bifunctional thiourea catalysts and applied such catalysts to asymmetric Mannich reaction of fluorinated ketoesters. More recently, this concept has been extended, and more catalysts of this nature and more enantioselective reactions have been developed.
Novel amino acid-incorporating multifunctional catalysts
By incorporating amino acid residues into the existing bifunctional catalyst scaffolds, we derivatized novel multifunctional catalysts, and their effectiveness has been demonstrated in the enantioselective conjugate addition of oxindoles to a vinyl sulfone. We have recently shown wide applications of such catalysts in a number of enantioselective transformations.
Novel bifunctional phosphines derived from amino acids/peptides
Very recently, we questioned the possibility of deriving novel chiral phosphines from amino acids/peptides, and in this context, we have developed a number of bifunctional phosphines that can be readily derived from natural amino acids and peptides. Our catalytic systems have been applied to enantioselective (aza)-Morita-Baylis-Hillman reactions, [3+2] cycloadditions, [4+2] cycloadditions, and allylic alkylations, among others.
Organic chemistry has played a central role in pharmaceutical industry and drug discovery. We are exploring certain therapeutic areas by approaches combining organic synthesis, structure-based drug design and computational chemistry. Specifically, we are interested in the development of novel opioid peptides/opiates, and potentially useful anti-cancer agents.
- Yao, W.; Dou, X.; Wen, S.; Wu, J.; Vittal, J. J.; Lu, Y. “Enantioselective Desymmetrization of Cyclohexadienones via an Intramolecular Rauhut–Currier Reaction of Allenoates”, Nat. Commun., 2016, 7, 13024.
- Wang, T.; Han, X.; Zhong, F.; Yao, W.; Lu, Y. “Amino Acid-derived Bifunctional Phosphines for Enantioselective Transformations”, Acc. Chem. Res., 2016, 49, 1369. (one of the Most Read Articles in July/August 2016).
- Dou, X.; Lu, Y.; Hayashi, T. “Base Free Conditions for Rhodium-Catalyzed Asymmetric Arylation to Produce Stereochemically Labile α-Aryl Ketones”, Angew. Chem. Int. Ed., 2016, 55, 6739 (highlighted in SYNFACTS 2016, 831).
- Han, X.; Chan, W.-L.; Yao, W., Wang, Y.; Lu, Y. “Phosphine-mediated Highly Enantioselective Spirocyclization with Ketimines as Substrates”, Angwe. Chem. Int. Ed., 2016, 55, 6492.
- Lu, Y. “Yixin Lu”, author profile, Angew. Chem. Int. Ed. 2016, 55, 2300.
- Wang, T.; Yu, Z.; Hoon, D. L.; Phee, C. Y.; Lan, Y.; Lu, Y. “Regiodivergent Enantioselective g-Additions of Oxazolones to 2,3-Butadienoates Catalyzed by Phosphines: Synthesis of a,a-Disubstituted a-Amino Acids and N,O-Acetal Derivatives”, J. Am. Chem. Soc. 2016, 138, 265 (highlighted in SYNFACTS 2016, 309).
- Xu, L.-W.; Chen, Y.; Lu, Y. “Catalytic Silylations of Alcohols: Turning Simple Protecting-Group Strategies into Powerful Enantioselective Synthetic Methods”, Angew. Chem. Int. Ed. 2015, 54, 9456.
- Yao, W.; Dou, X.; Lu, Y. “Highly Enantioselective Synthesis of 3,4-Dihydropyrans through a Phosphine-Catalyzed [4 + 2] Annulation of Allenones and b,g-Unsaturated a-Keto Esters”, J. Am. Chem. Soc., 2015, 137, 54 (highlighted in SYNFACTS 2015, 201).
- Jiang, C.; Lu, Y.;* Hayashi, T.* “High Performance of a Palladium-Phosphinooxazoline Catalyst in Asymmetric Arylation of Cyclic N-Sulfonyl Ketimines”, Angew. Chem. Int. Ed. 2014, 53, 9936 (highlighted in SYNFACTS 2014, 1203).
- Han, X.; Yao, W.; Wang, T.; Tan, Y. R.; Yan, Z.; Kwistkowski, J.; Lu, Y. “Asymmetric Synthesis of Spiropyrazolones via Phosphine-Catalyzed [4+1] Annulations”, Angew. Chem. Int. Ed. 2014, 53, 5643. (highlighted by Organic Chemistry Portal; link: http://www.organic-chemistry.org/Highlights/2014/08December.shtm)
- Wang, T.; Yao, W.; Zhong, F.; Pang, G. H.; Lu, Y. “Phosphine Catalyzed Enantioselective g-Addition of 3-Substituted Oxindoles to 2,3-Butadienoates and 2-Butynoates: Use of Prochiral Nucleophiles”, Angew. Chem. Int. Ed. 2014, 53, 2964.
- Zhong, F.; Dou, X.; Han, X.; Yao, W.; Zhu, Q.; Meng, Y.; Lu, Y. “Chiral Phosphine-Catalyzed Asymmetric Michael Addition of Oxindoles”, Angew. Chem. Int. Ed. 2013, 52, 943 (highlighted in SYNFACTS 2013, 216).
- Zhong, F.; Luo, J.; Chen, G.-Y.; Dou, X.; Lu, Y. “Highly enantioselective regiodivergent allylic alkylation of MBH carbonates with phthalides”, J. Am. Chem. Soc. 2012, 134, 10222 (highlighted in SYNFACTS 2012, 906).
- Han, X.; Zhong, F.; Wang, Y.; Lu, Y. “Versatile Enantioselective [3+2] Cyclization between Imines and Allenoates Catalyzed by Dipeptide-Based Phosphines”, Angew. Chem. Int. Ed. 2012, 51, 767 (highlighted in SYNFACTS 2012, 331; also by Organic Chemistry Portal; link: http://www.organic-chemistry.org/Highlights/2012/19November.shtm).
- Zhong, F.; Han, X.; Wang, Y.; Lu, Y. “Highly Enantioselective [3+2] Annulation of Morita-Baylis-Hillman Adducts Mediated by L-Threonine-Derived Phosphines: Synthesis of 3-Spirocyclopentene-2-oxindole having Two Contiguous Quaternary Centers”, Angew. Chem. Int. Ed. 2011, 50, 7837 (highlighted in SYNFACTS 2011, 1020; one of the most cited Angew. Chem. Communications published in 2011/2012).
- Han, X.; Wang, Y.; Zhong, F.; Lu, Y. “Enantioselective [3+2] Cycloaddition of Allenes to Acrylates Catalyzed by Dipeptide-derived Novel Phosphines: Facile Creation of Functionalized Cyclopentenes Containing Quaternary Stereogenic Centers”, J. Am. Chem. Soc. 2011, 133, 1726. (No. 1 JACS most-read article in January/February 2011; highlighted in SYNFACTS 2011, 442, highlighted by Organic Chemistry Portal;
- Luo, J.; Wang, H.; Han, X.; Xu, L.-W.; Kwiatkowski, J.; Huang, K.-W.; Lu, Y. “The Direct Asymmetric Vinylogous Aldol Reaction of Furanones with a-Ketoesters: Access to Chiral g-butenolides and Glycerol Derivatives”, Angew. Chem. Int. Ed. 2011, 50, 1861. (highlighted in SYNFACTS 2011, 445; highlighted by Organic Chemistry Portal; link: www.organic-chemistry.org/Highlights/2012/27February.shtm)