Cong-Gui Zhao

Cong-Gui Zhao received his MS degree from the renowned Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences (with Professor Rong-Yu Zhang), and his PhD from the University of Würzburg, Germany (with Professor Waldemar Adam).

Our major research focus is to conduct organic reactions in a green manner, aiming at high selectivities (chemo-,
regio-, diastereo- and enantioselectivity). Our current research areas include: Asymmetric reaction and catalysis; small-ring compounds; oxidation; and organophosphorus compounds. Instead of isolating these areas, we try to combine two or more of them together in our studies to gain better insights and/or results.

Asymmetric reaction and catalysis:

We are interested in developing novel organocatalysts for enantioselective reactions, such as, direct aldol reaction, Michael reaction, and Diels-Alder reaction, direct nitro-Michael addition, etc. Our goal is to find catalysts that are highly enantioselective, highly efficient in catalytic activity and tolerating very broad substrate classes. For example, we have developed 1,2-diamine N,N’-diamide-type catalysts that can achieve up to >99% ee in direct asymmetric aldol reactions with as little as 5 mol % loading of the catalyst.

Currently we are vigorously pursuing the idea of using modularly designed self-assemblies as the organocatalysts for asymmetric reactions (Scheme 1). This new method for the formation of organocatalysts drastically reduces the efforts required for the synthesis and modification of an organocatalyst.

Scheme 1. Modularly Designed Organic Self-Assembly for Highly Enantioselective Direct Nitro-Michael Addition

Small-ring compounds and oxidation:

We are also interested in small-ring compounds, such as, dioxirane, metalloperoxo complexes (e.g., those of MTO, etc.), cyclopropane, oxaziridinium salt, and episulfide. Due to ring strains or weaker bonds, these compounds normally exhibit unusual reactivity, which may be manipulated for developing very useful synthetic methodologies. For example, we have developed the first catalytic highly enantioselective CH oxidation method with chiral dioxiranes (Scheme 2).

Scheme 2. Catalytic Highly Enantioselective CH Oxidation of vic-Diols

Organophosphorus compounds:

Organophoshorus compounds are highly biologically active compounds and have found many uses in medicinal, industrial and agricultural applications. Among them, a-hydroxyphosphonic acid and a-hydroxyphosphinic acid derivatives are very important enzyme inhibitors, and have been applied in anti-virus and anti-cancer studies (Scheme 3). Our group has recently developed a novel synthesis of optically active a-hydroxyphosphonates and a-hydroxyphosphinates in highly enantioselective manner (Scheme 4). Preliminary screening of these novel organophosphorus compounds shows strong biological activities. Currently we are also seeking novel enantioselective methods for the synthesis of a-aminophosphonates and a-aminophosphinates, which are strong enzyme inhibitors, too.

Scheme 3. Reported Examples of Biologically Active a-Hydroxyphosphonic and a-Hydroxyphosphinic Acid Derivatives

Scheme 4. Highly Enantioselective Synthesis of a-Hydroxyphosphonates and a-Hydroxyphosphinates

Selected Publications: (since 2003)

1. Zhao, C.-G.,* Adam, W. "Dioxirane Oxidations" Organic Reactions, submitted.
2. Mandal, T.; Zhao, C.-G.* "Modularly Designed Organocatalytic Assemblies for Direct Nitro-Michael Addition Reactions" Angew. Chem. Int. Ed. 2008, 47, in press.
3. Dodda, R.; Mandal, T.; Zhao, C.-G.* “Organocatalytic Highly Enantioselective Tandem Michael-Knoevenagel Reaction for the Synthesis of Substituted Thiochromanes” Tetrahedron Lett., 2008, 49, 1899-1902.
4. Dodda, R.; Goldman, J. J.; Mandal, T.; Zhao, C.-G.*; Broker, G. A.; Tiekink, E. R.T. “Synthesis of 2,3,4-Trisubstituted Thiochromanes Using an Organocatalytic Enantioselective Tandem Michael-Henry Reaction” Adv. Synth. Catl., 2008, 350, 537-541.
5. Adam, W.; Zhao, C.-G.,* Jakka, K. “Dioxirane Oxidations of Compounds Other than Alkenes” Org. React., 2007, 69, 1-346.
6. Samanta, S.; Zhao, C.-G.* “Organocatalytic Nitroaldol Reaction of a-Ketophosphonates and Nitromethane Revisited” Arkivoc, 2007, (13), 218-226.
7. Mandal, T.; Zhao, C.-G.* “Synthesis of Prolinal Dithioacetals as Catalysts for the Highly Stereoselective Michael Addition of Ketones and Aldehydes to β-Nitrostyrenes” Tetrahedron Lett., 2007, 48, 5803-5806.
8. Samanta, S.; Krause, J.; Mandal, T.; Zhao, C.-G.* “Inverse-Electron-Demand Hetero-Diels-Alder Reaction of b,g-Unsaturated a-Ketophosphonates Catalyzed by Prolinal Dithioacetals” Org. Lett., 2007, 9, 2745-2748.(Highlighted by Organic-Chemistry.org. )
9. Dodda, R.; Zhao, C.-G.* “Enantioselective synthesis of a-aminopropargylphosphonates” Tetrahedron Lett., 2007, 48, 4339-4342.
10. Dodda, R.; Zhao, C.-G.* “Organocatalytic Enantioselective Synthesis of Secondary a-Hydroxycarboxylic Esters” Synlett, 2007, 1605-1609.
11. Mandal, T.; Samanta, S.; Zhao, C.-G. “Organocatalytic Highly Enantioselective Nitroaldol Reaction of a-Ketophosphonates and Nitromethane” Org. Lett. 2007, 9, 943-945.
12. Jakka, K.; Liu, J.; Zhao, C.-G.* “Facile Epoxidation of a,b-Unsaturated Ketones with Cyclohexylidenebishydroperoixde” Tetrahedron Lett., 2007, 48, 1395-1398.
13. Dodda, R.; Zhao, C.-G.* “Silver(I) Triflate-Catalyzed Direct Synthesis of
    N-PMP Protected a-Aminopropargylphosphonates from Terminal Alkynes” Org. Lett., 2007, 9, 165-167. (Highlighted by Organic-Chemistry.org. )
14. Dodda, R.; Zhao, C.-G.* “Organocatalytic Highly Enantioselective Synthesis of Secondary a-Hydroxyphosphonates” Org. Lett., 2006, 8, 4911-4914. [Highlighted by Synfacts (2006, Page 1282)]
15. Jakka, K.; Zhao, C.-G.  “Catalytic Highly Enantioselective CH Oxidation of vic-Diols with Shi’s Oxazolidinone Dioxiranes” Org. Lett., 2006, 8, 3013-3015.
16. Samanta, S.; Zhao, C.-G. “Organocatalytic Enantioselective Synthesis of a-Hydroxy Phosphonates” J. Am. Chem. Soc.,2006, 128, 7442-7443. (One of the Top 25 Hottest Articles of the Tetrahedron Lett.)
17. Samanta, S.; Zhao, C.-G. ''Organocatalytic Asymmetric Direct Aldol Reaction of 1,2-Ketones and Ketones ''  Tetrahedron Lett., 2006, 47, 3383-3386.
18. Dodda, R.; Zhao, C.-G.* “L-Proline Catalyzed One-Pot Three-Component Reaction for the Synthesis of b-Alkoxy Ketones” Synthesis, 2006, 3238-3242.
19. Adam, W.; Zhao, C.-G. “Chapter 16. Contemporary Dioxirane Chemistry: Epoxidations, Heteroatom Oxidations and CH Insertions”, in The Chemistry of Peroxides; Rappoport, Z. Ed; Wiley:Chichester, Vol. 2, 2006, pp. 1129-1170.
20. Adam, W.; Zhao, C.-G. “Chapter IV. 2.1.2 Oxidation of Unactivated Alkanes by Dioxiranes”, in Handbook of CH Transformations, Applications in Organic Synthesis; Dyker, G. Ed; Wiley-VCH:Weinheim, Vol. 2, 2005, pp 507-516.
21. Samanta, S., Liu, J.; Dodda, R.; Zhao, C.-G. ''C₂-Symmetric Bisprolinamide as Highly Efficient Catalyst for Direct Aldol Reaction'' Org. Lett., 2005, 7, 5221-5123. (One of the ACS Most Accessed Articles and Highlighted by the Organic-Chemistry.org )
22. Chakraborty, R.; Franz, V.; Bez, G.; Dipali, V.; Popuri, C.; Zhao, C.-G. ''Some New Aspects of the Boyer Reaction'' Org. Lett., 2005, 7, 4145-4148.
23. Bez, G.; Zhao, C.-G. “First Highly Enantioselective Epoxidation of Alkenes with Aldehyde/Oxoneâ” Tetrahedron Lett., 2003, 44, 7403-7406. 
24. Bez, G.; Zhao, C.-G. ''Gallium(III) Chloride-Catalyzed Double Insertion of Isocyanides into Epoxides'' Org. Lett., 2003, 5, 4991-4993.