Andrew , Wee - University of Regina - Department of Chemistry and Biochemistry

个人简介

B.Sc (1st Class Hons), University of London, UK PhD, University of London, UK PDF (Stanford University, Duke University and University of Alberta) University of Regina Inspiring Teacher Award

研究领域

There is an increasing demand for organic molecules with diverse structural features for use in, e.g., the manufacturing of new materials, in the discovery of new medicines and for use as "tools" in our understanding of biochemical processes, which would have important implications in medicine. Some of them are not made by nature and those that are, are only available in small amounts. Organic synthesis is the method of choice for making these molecules available and in sufficient quantities so that studies on their (bio)chemical and physical properties can be conducted. My research is concerned with the design and preparation of new rhodium metal derivatives and their use in catalyzing the formation of new carbon-carbon bonds-a fundamental process in organic synthesis. These new methods will be used for making relatively complex molecules from simple organic building blocks. The ultimate goal in these studies is to develop practical methods that can be used for the synthesis of medicinally important, biologically active compounds. New drugs, such as anticancer, antihypertensive, anti-alzheimer drugs, that can have potential health benefit applications may be discovered. Rh(II)-carbenoid chemistry: My research interests are (1) the development of new methods for the preparation of heterocyclic compounds, and (2) application of the methods in the synthesis of natural and non-natural, biologically active and/or medicinally important molecules. My ongoing and primary investigations are centred on the dirhodium(II)-catalyzed reactions of diazocarbonyl compounds for the construction of O- and N-heterocycles (e.g., lactones and lactams). Compounds possessing the g-lactam and g-lactone ring systems are widespread in nature and most of them also possess interesting biological activities. As well, g-lactams and g-lactones can serve as useful intermediates for the synthesis of more complex natural products such as alkaloids. We have investigated the intramolecular C-H insertion reaction of diazoamides and esters, which represents one of the most versatile methods available for the construction of g-lactam and g-lactone ring systems. We have successfully developed a "chiral auxiliary" approach for the synthesis of 4-substituted g-lactams. Present efforts are aimed at further improving the enantioselectivity of the reaction. We are also investigating 1,2- and 1,3- relative induction as well as double stereoselection strategies for effecting asymmetric C-H insertion. Another area that is being studied is the asymmetric tandem sulfonium ylide/[2,3]-sigmatropic rearrangement reaction. Once developed, this method should provide ready access to chiral, non-racemic highly functionalized products that would serve as versatile intermediates for the synthesis of more complex molecules. A challenging aspect of our studies is the design and development of novel routes for the construction of quaternary carbon centres, which are important sub-structural features found in the carbon framework of many biologically active, natural products. Asymmetric dirhodium(II)-carbenoid mediated organic transformations (C-H insertion, tandem sulfonium ylide rearrangement reaction) are being studied and developed as methods for the synthesis of molecules possessing quaternary centres. "Chiral pool" synthesis: This is a secondary area of our research. We have achieved the total synthesis of natural products using "chiral pool" starting material, in particular, sugars. For example, we have prepared an enantiomeric pair of 4- and 5-oxazolidinonecarbaldehydes from D-ribose and D-mannose and have used these aldehydes in the synthesis of C18-ribo-phytosphingosine, an important amino alcohol structural component in glycosphingolipids, and an alkaloid (2S,3R)-3-hydroxy-2-(hydroxymethyl)pyrrolidine. This area is also relevant to our primary objective because "chiral pool" starting materials are also used for the preparation of our diazo substrates, chiral auxiliary and chiral ligands. The knowledge gained through these studies should provide the essential elements for achieving control over the reactions of organic processes. The long term goals of my research program is the application of the methods that have been developed to the synthesis of natural and non-natural products.

近期论文

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Wee, A.G.H. Rhodium(II)-catalyzed reaction of diazocompounds in the service of organic synthesis of natural and non-natural products. Curr. Org. Syn. 2006, 3, 499-555. Fan, G.-J.; Wang, Z.; Wee, A.G.H. Regio- and diastereocontrolled C-H insertion of chiral g- and d-lactam diazoacetates. Application to the asymmetric synthesis of (8S,8aS)-8-hydroxyindolizidine. Chem. Commun. 2006, 3732-3734. Wang, Z.; Wee, A.G.H.; Hepperle, S.S.; Treble, R.G.; East, A.L.L. Competing isomerizations: A combined experimental/theoretical study of phenylpentenone isomerism. J. Phys. Chem. A 2006, 110, 5985-5989. Wee, A.G.H.; Duncan, S.C.; Fan, G.-J. Intramolecular asymmetric C-H insertion of N-arylalkyl,N-bis(trimethylsilyl)methyldiazoamides mediated by rhodium(II) catalysts. Synthesis of (R)-b-benzyl-g-aminobutyric acid. Tetrahedron: Asymmetry, 2006, 17, 297-307. Wee, A.G.H.; McLeod, D.D. A stereoselective synthesis of the non-proteinogenic amino acid (2S,3R)-3-amino-a-hydroxydecanoic acid from (4S,5S)-4-formyl-5-vinyl-2-oxazolidinone. J. Org. Chem. 2003, 68, 6268-6273. Wee, A.G.H.; Shi, Q.; Wang, Z.; Hatton, K. Diastereoselective rhodium(II)-catalyzed sulfonium ylide formation-[2,3]-sigmatropic reaction of chiral non-racemic allylic sulfides (invited) Tetrahedron: Asymmetry, 2003, 14, 897-909. (Special Edition, H. M. L. Davies, ed) Doyle, M.P.; Hu, W.; Wee, A.G.H.; Wang, Z.; Duncan, S.C. Influences of catalyst configuration and catalyst loading on selectivities in reactions of diazoacetamides. Barrier to equilibrium between diastereomeric conformations. Org. Lett. 2003, 5, 407-410. Wee, A.G.H.; Duncan, S. C. The rhodium(II)-catalyzed reaction of N-bis(trimethylsilyl)methyldiazoamides: steric, electronic and conformational effects. Tetrahedron Lett. 2002, 43, 6173-6176. Wee, A.G.H. A dirhodium(II)-carbenoid route to (-)- and (+)-Geissman-Waiss lactone: Synthesis of (1R,7R,8R)-(-)-turneforcidine. J. Org. Chem. 2001, 66, 8513-8517. Wee, A.G.H.; Yu, Q. Asymmetric synthesis of (-)-eburnamonine and (+)-epi-eburnamonine from (4S)-4-ethyl-4-[2-(hydroxycarbonyl)ethyl]-2-butyrolactone. J. Org. Chem. 2001, 66, 8935-8943. Wee, A.G.H. A Facile Synthesis of (-)- and (+)-Geissman-Waiss Lactone via Intramolecular Rh(II)-Carbenoid Mediated C-H Insertion Reaction: Synthesis of (1R,7R,8R)-Turneforcidine. Tetrahedron Lett. 2000, 41, 9025-9029. Doyle, M. P.; Hu, W, Phillips, I, Wee, A.G.H. A New Approach To Macrocyclization via Alkene Formation in Catalytic Diazo Decomposition. Synthesis of Patulolides A and B. Org. Lett. 2000, 2, 1777-1779. Wee, A.G.H.; Yu, Q. Total Synthesis of (-)-Eburnamonine and (+)-epi-Eburnamonine From A Common Chiral Non-Racemic g-Lactone Carboxylic Acid. Tetrahedron Lett. 2000, 41, 587-590.