Gregory K. Friestad

Gregory K. Friestad
Associate Professor
E455 CB
  • B.S., Bradley University (1990)
  • Ph.D., University of Oregon (1995)
  • NIH Postdoctoral Fellowship, University of Pennsylvania (1995-1998)
  • Visiting Professor and JSPS Fellowship, Kobe Pharmaceutical University (2003)
  • Visiting Professor, University of Wisconsin-Madison (2005)

Synthetic methodology and natural product synthesis, emphasizing chiral amines, stereoselective carbon-carbon bond constructions, radical addition reactions, organometallic reagents, and asymmetric catalysis.

Research Interests: 

Organic synthesis is crucial to biomedical research and nanotechnology because organic chemists design and provide new substances with the improved properties needed to achieve the amazing advances we see in these areas. Fundamental basic research in organic chemistry allows us to make new substances more efficiently, and with less environmental impact.

Researchers in the Friestad Group address problems in synthetic methodology and natural product synthesis, with special emphasis on efficiency by developing useful carbon-carbon bond constructions. Our primary synthetic targets are biologically active substances which have significant potential either as biological probes in health sciences research or as lead compounds for development of new disease therapies. Students develop new synthetic methods and apply them to natural product targets, routinely using research instrumentation such as nuclear magnetic resonance (NMR) and high-performance liquid chromatography (HPLC). Such projects, combining the depth of methodology research with the breadth of total synthesis training, are outstanding preparation for industrial or academic research. Friestad Group alumni have careers in pharmaceutical companies both big and small, as well as teaching and research positions in academia.

Specific projects we have developed involve reaction methodology at the interface with organometallic chemistry, ranging from organosilicon and organotransition metal chemistry to free radical reactions. We've developed silicon-tethered diastereoselective radical cyclizations leading to amino alcohols. We've designed and implemented a novel chiral N-acylhydrazone motif for asymmetric addition reactions which provides for excellent enantioselectivity from chiral auxiliaries or catalysts. Our chiral N-acylhydrazones have proved to be broadly useful acceptors for additions of alkyl radicals and a wide range of nucleophiles including hydride and allylsilane reagents. We found that photolysis of Mn2(CO)10 enables radical addition to chiral N-acylhydrazones using a broad range of precursors, including primary alkyl halides and multifunctional compounds. This method is now in use for synthesis of complex natural product targets.

 New Synthetic Methods and Applications

Recent Publications: 
  • Friedrich, R. M.; Bell, J. Q.; Garcia, A.; Shen, Z.; Friestad, G. K. "Unified Strategy for 1,5,9- and 1,5,7-Triols via Configuration-Encoded 1,5-Polyol Synthesis: Preparation and Coupling of C15–C25 and C26–C40 Fragments of Tetrafibricin." Journal of Organic Chemistry 2018, 83, 13650-13669.  (Featured Article)  PDF:

  • Friedrich, R. M.; Sreenilayam, G.; Hackbarth, J.; Friestad, G. K. "Unified Strategy for 1,5,9- and 1,5,7-Triols via Configuration-Encoded 1,5-Polyol Synthesis: Enantioselective Preparation of gamma-Sulfonyl-alpha-silyloxyaldehydes and Iterative Julia–Kocienski Coupling." Journal of Organic Chemistry 2018, 83, 13636-13649.  (Featured Article)  PDF:

  • Ibrahim, S. M. S.; Banerjee, K.; Slater, K. A.; Friestad, G. K. "A Tamao-Fleming oxidation route to dipeptides bearing N,O-acetal functionality." Tetrahedron Letters 2017, 58, 4864-4866.  PDF:

  • Friedrich, R. M.; Friestad, G. K. "Access to an anti,syn-1,5,7-Triol by Configuration-Encoded 1,5-Polyol Synthesis: The C15–C25 Fragment of Tetrafibricin." European Journal of Organic Chemistry 2017, 1961-1964.  PDF:

  • Friestad; G. K.; Banerjee, K.; Marié, J.-C.; Mali, U.; Yao, L. “Stereoselective Access to Tubuphenylalanine and Tubuvaline: Improved Mn-Mediated Radical Additions and Assembly of A Tubulysin Tetrapeptide Analog” Journal of Antibiotics 2016, 69, 294-298.   PDF:

  • Slater, K. A.; Friestad, G. K. “Mn-Mediated Radical-Ionic Annulations of Chiral N-Acylhydrazones.” Journal of Organic Chemistry 2015, 80, 6432-6440.  PDF:

  • Friestad, G. K. "Control of Asymmetry in the Radical Addition Approach to Chiral Amine Synthesis" In Topics In Current Chemistry: Stereoselective Formation of Amines; Li, W.; Zhang, X., Eds.; Springer-Verlag: Berlin, 2014, vol. 343, pp. 1-32.

  • Xu, X.; Friestad, G. K.; Yao, L."Recent Advances in the Synthesis of Tubulysins" Mini-Reviews in Medicinal Chemistry 2013, 13, 1572-1578.  PDF:

  • Friestad, G. K.; Sreenilayam, G.; Cannistra, J. C.; Slominski, L. M. "Preparation of Enol Ester Epoxides and Their Ring-Opening to alpha-Silyloxyaldehydes." Tetrahedron Letters 2012, 53, 5064-5067.  PDF:

  • Friestad, G. K. "Asymmetric Radical Addition to Chiral Hydrazones." In Topics In Current Chemistry: Radicals in Synthesis III; Gansauer A.; Heinrich, M., Eds., Springer-Verlag: Berlin, 2012, vol. 320, pp. 61-92

  • Friestad, G. K. "Organomanganese-Mediated Radical Reactions." In The Chemistry of Organo-Manganese Compounds; Marek, I.; Rappoport, Z., Eds.; Wiley: Chichester, United Kingdom, 2011, pp. 559-584.  [PDF]

  • Friestad, G. K.; Ji, A.; Korapala, C. S.; Qin, J.  "Intermolecular Radical Addition to N-Acylhydrazones as a Stereocontrol Strategy for Alkaloid Synthesis: Formal Synthesis of Quinine." Organic and Biomolecular Chemistry 2011, 4039-4043.   [PDF]

  • Friestad, G. K.; Sreenilayam, G. "1,5-Polyols: Challenging Motifs for Configurational Assignment and Synthesis." Pure and Applied Chemistry 2011, 83, 461-478.  [PDF]

  • Friestad, G.K.; Ji, A.; Baltrusaitis, J.; Korapala, C.S.; Qin, J.  Scope of Stereoselective Mn-Mediated Radical Addition to Chiral Hydrazones and Application in a Formal Synthesis of Quinine. Journal of Organic Chemistry 2012, 77, 3159-3180.

  • Friestad, G.K.; Sreenilayam, G.  Versatile Configuration-Encoded Strategy for Rapid Synthesis of 1,sd5-Polyol Stereoisomers. Organic Letters 2010, 12, 5016-5019.

  • Friestad, G.K.; Ji, A.  Mn-Mediated Coupling of Alkyl Iodides and Ketimines: A Radical Addition Route to alpha,alpha-Disubstituted alpha-Aminoesters. Organic Letters, 2008, 10, 2311-2313.

  • Friestad, G.K.; Qin, J; Suh, Y.; Marié, J.C.   Mn-Mediated Coupling of Alkyl Iodides and Chiral N-Acylhydrazones: Optimization, Scope, and Evidence for a Radical Mechanism. Journal of Organic Chemistry  2006, 71, 7016-7027.

  • Friestad, G.K.; Deveau, A. M.; Marié, J.C.  Stereoselective Mn-Mediated Coupling of Functionalized Iodides and Hydrazones: A Synthetic Entry to the Tubulysin gamma-Amino Acids.  Organic Letters 2004, 6, 3249-3252.

  • Ding, H.; Friestad, G.K.  Trifluoroacetyl-Activated Nitrogen-Nitrogen Bond Cleavage of Hydrazines by Samarium (II) Iodide. Organic Letters 2004, 6, 637-640.

  • Friestad, G.K.; Shen, Y.; Ruggles, E.L.  Enantioselective Radical Addition to N-Acyl-hydrazones Mediated by Chiral Lewis Acids. Angewandte Chemie International Edition 2003, 42, 5061-5063.

  • Friestad, G.K.; Qin, J.  Intermolecular Alkyl Radical Addition to Chiral N-Acylhydrazones Mediated by Manganese Carbonyl.  Journal of the American Chemical Society  2001, 123, 9922-9923.

  • Friestad, G.K.; Ding, H.   Asymmetric Allylsilane Additions to Enantiopure N-Acylhydrazones with Dual Activation by Fluoride and In(OTf)3Angewandte Chemie International Edition 2001, 40, 4491-4493.

  • Friestad, G.K.; Qin, J.   Highly Stereoselective Intermolecular Radical Addition to Aldehyde Hydrazones from a Chiral 3-Amino-2-oxazolidinone. Journal of the American Chemical Society 2000, 122, 8329-8330.