Melanie Sanford
University of Michigan, MI·Chemistry
Most of the reactions that build medicines rely on catalysts made from precious metals such as palladium, rhodium and iridium, which are rare and expensive. At the same time, chemists often need to modify a complicated drug molecule at a late stage rather than rebuilding it from scratch, a goal that current methods handle poorly.
- Fields
Chemistry
Pharmacology
- Topics
C–H functionalization
C–H activation
homogeneous catalysis
- Grants
- 2 known grants, through Jun 2030
What they work on
- Determine the mechanisms of cyclometalation and oxidative functionalization in copper, nickel and iron pincer complexes, varying the bidentate directing group, supporting ligands and oxidant to see how each controls the pathway.
- Isolate or detect the key reactive intermediates in first-row metal C–H functionalization using fluorine-19 NMR spectroscopy to monitor both ordinary and paramagnetic species in situ.
- Apply palladium-catalyzed C–H functionalization to strained cycloalkane benzene bioisosteres, three-dimensional replacements for flat aromatic rings that drug developers increasingly use.
- Develop photocatalysts for C–H pyridination of arenes and heteroarenes, and use the resulting N-arylpyridinium salts as building blocks for downstream functionalization.
- Exploit stereoretentive CO de-insertion and reductive elimination to achieve stereospecific decarbonylative couplings of chiral pool carboxylic acids.
- Use decarbonylative methods to convert carboxylic acids in complex molecules directly into bioisosteres such as tetrazoles and sulfonamides, avoiding de novo synthesis of each analogue.
- Develop new metal-catalyzed routes to aryl and heteroaryl fluorides, and reagents and catalysts for installing fluorinated sulfur and oxygen substituents onto aromatic cores.
More about the research
Two programs address these problems: one works out the fundamental mechanisms by which cheap, abundant metals can carry out carbon–hydrogen bond chemistry, and the other develops practical synthetic methods for making and diversifying biologically active molecules, guided throughout by mechanistic study.
Why it matters
Replacing scarce precious metals with copper, nickel and iron in C–H activation chemistry could lower the cost and improve the supply security of reactions used throughout the chemical and pharmaceutical industries. Methods that swap a carboxylic acid for a tetrazole or sulfonamide, or install fluorine-containing groups late in a synthesis, could speed drug discovery by letting chemists make analogues without rebuilding each one. The fluorination routes are also relevant to radiochemistry for imaging agents. The program trains chemistry PhD students and runs hands-on electrochemistry outreach, including building voltaic piles, with Michigan middle and high school students.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Paul Chirik
Princeton University, NJ·Chemistry
Discover robust iron and cobalt catalyst precursors in several oxidation states, using oxidatively-induced reductive elimination and arene displacement from metal sandwich compounds.
Mark Biscoe
CUNY City College, NY·Chemistry
Develop palladium- and copper-catalyzed cross-coupling reactions that transfer handedness from enantioenriched secondary alkylboron reagents to new carbon centers with predictable retention or inversion.
Byoungmoo Kim
Clemson University, SC·Chemistry
Develop one-step, stereospecific and site-selective deoxygenative amination of alcohols, replacing the C–O bond with free amines or nitrogen-containing rings, using a sulfonyl fluoride reagent that reacts through SuFEx click chemistry.
The school
University of Michigan: 124 labs on PI Pages, $2.1B a year on research, 963 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.