CRAIG A. MERLIC, Associate Professor

(b. 1959) B.S. 1982, University of California, Davis; Ph.D. 1988, University of Wisconsin, Madison; NIH Postdoctoral Fellow 1988-1989, Princeton University; National Science Foundation Young Investigator Award, 1992-1997.

Our research program in organic and organometallic chemistry encompasses synthetic organic, synthetic organometallic, and physical organometallic chemistry. Research goals include discovery of new reactions and catalysts, development of synthetic methods, determination of reaction mechanisms, analysis of reaction selectivity, synthesis of bioactive natural products and development of organometallic complexes for materials research. The development of new chemistry using organometallic species is a rich and fertile area due to the unique ability of transition metal fragments to impart special reactivity, selectivity, and stability upon bonded organic moieties. Our research draws on these features to address problems in organic synthesis.

Organometallic Radical Reactions for Stereoselective Synthesis

Organometallic radical reactions are being investigated as new methods for carbon- carbon bond formation. By using transition metal fragments to template the reactions of organic moieties, complete control of chemoselectivity, regiochemistry and stereochemistry in radical cyclizations will be feasible. A wide array of organometallic compounds are employed including iron olefin complexes, cobalt alkyne complexes, iron triene complexes, chromium carbenes and arene chromium complexes. Applications of the newly developed methodologies to the syntheses of biologically active products such as antitumor agents, unnatural sugars, and antibiotics are under investigation.

Synthesis Via Metal-Mediated Pericyclic Reactions

We are exploring fundamentally new types of pericyclic reactions by incorporating metal fragments into reacting polyene arrays. The metals can participate directly in pericyclic reactions or can serve as templates to control reaction selectivity. Examples include chromium carbene annulations that provide ortho substituted phenols under photolytic conditions or cyclopentadienes via thermolysis and a chromium analogue of the Claisen rearrangement. Second generation reactions will employ metal fragments catalytically. Topics we seek to address in organometallic pericyclic reactions include reaction mechanisms, selectivity rules, substrate variability and synthetic applications. These new methodologies are applied to the synthesis of a number of structurally diverse antibiotic and antitumor agents including Illudin M and A51493A and a protein kinase inhibitor K-254a.

Organometallic Stereoelectronics

The conformation, stereochemistry and reactivity of many organic molecules are controlled by stereoelectronic effects. Our aim is to develop the theory of organometallic stereoelectronics and to elucidate stereoelectronic effects controlling the structure, reactivity and stereoselectivity in the reactions of organometallic compounds. In contrast with organic compounds, the ability to alter ligands to fine tune the electronics of organometallic complexes provides a unique feature which aids in the study of stereoelectronic effects. Classes of compounds under study include boron metallocycles, metal substituted sugar and dioxane derivatives, chromium carbene complexes and iron and platinum alkene complexes. The insights gained will be applied to stereocontrolled organic and organometallic synthesis.

Molecular Dynamics and Molecular Switches

A variety of transition metal moieties exhibit remarkable selectivity in their mobility when attached to polyene and polyenyl organic compounds. New methods of controlling this fluxional coordination of polyene arrays to transition metals are under study in order to elucidate the nature of bonding changes and explore the potential for electronic devices. The molecular dynamics of these fluxional processes present interesting challenges to structural analysis and characterization. Discoveries in this area will be utilized for the development of novel types of molecular switching devices such as three state switches.

Representative Publications

  1. Trost, B.M.; Merlic, C.A. "Geminal Alkylation - Substitutions of Allyl Sulfones. Regiocontrol via Molybdenum Catalysis," J. Org. Chem. 1990, 55, 1127-1129.
  2. Trost, B.M.; Merlic, C.A. "Ligand Dependence of Molybdenum Catalyzed Alkylations. Molybdenum Isonitrile Complexes as a New Class of Highly Reactive Alkylation Catalysts," J. Am. Chem. Soc. 1990, 112, 9590-9600.
  3. Merlic, C.A.; Semmelhack, M.F. "An Interesting Chloride Ion Effect in the Heck Reaction," J. Organomet. Chem. 1990, 391, C23-C27.
  4. Merlic, C.A.; Xu, D. "Cyclization Reactions of Chromium Dienylcarbene Complexes. Entry to Ortho Substituted Aromatic Alcohols via a Designed Photoreaction" J. Am. Chem. Soc. 1991, 113, 7418-7420.
  5. Merlic, C.A.; Xu, D. "Intermolecular Radical Reactions of Unsaturated Chromium and Tungsten Carbene Complexes," J. Am. Chem. Soc. 1991, 113, 9855-9856.
  6. Merlic, C.A.; Xu, D.; Khan, S. I. "Synthesis, Structure and Reactivity of Cyclic Arene Chromium Carbene Complexes" Organometallics 1992, 11, 412-418.
  7. Merlic, C.A.; Adams, B. "Molybdenum-95 Nuclear Magnetic Resonance Studies on Molybdenum Carbonyl Complexes of Isonitriles and Amines" J. Organomet. Chem. 1992,431, 313-325.
  8. Merlic, C.A.; Burns, E. E.; Xu, D.; Chen, S. Y. "Aminobenzannulation Via Metathesis of Isonitriles Using Chromium Carbene Complexes" J. Am. Chem. Soc. 1992, 114, 8722.
  9. Merlic, C.A.; Xu, D; Gladstone, B. G. "Aminobenzannulation Via Photocyclization Reactions of Chromium Dienyl(amino)carbene Complexes. Synthesis of Ortho Amino Aromatic Alcohols" J. Org. Chem. 1993, 58, 538-545.
  10. Merlic, C.A.; Bendorf, H. A. "Titanium-Templated [4+2] Oxidative Cycloadditions: A Facile Route to 7-Hydroxynorbornenes" Organometallics 1993, 12, 559-564.
  11. Merlic, C. A.; Xu, D.; Nguyen, M. C.; Truong, V. " Stereochemistry of Intermolecular Radical Reactions of Unsaturated Tungsten Carbene Complexes," Tetrahedron Lett. 1993, 34, 227-230.
  12. Merlic, C. A.; Burns, E. E. "Chemoselectivity in the Isonitrile Metathesis Route to Aromatic Amines" Tetrahedron Lett. 1993, 34, 5401.
  13. Merlic, C. A.; Roberts, W. M. "Regioselectivity of Photochemical Annulations of Chromium Carbene Complexes" Tetrahedron Lett. 1993, 34, 7379.
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