New Methods for the Oxidative Functionalization of Carbon–Hydrogen Bonds
The development of methods for the oxidative transformation of inert C–H bonds into new functional groups (e.g., alcohols, esters, ethers, amines, halides, carbon-carbon bonds) remains a tremendous challenge in organic synthesis. Such procedures have the potential to fundamentally change the way chemists approach the assembly and late-stage modification of natural products, drug candidates, organic materials, and fine chemicals. There are three major challenges in this area: (i) C–H bonds are typically strong and kinetically inert (therefore harsh conditions are often required to achieve C–H bond activation), (ii) chemoselective oxidation is challenging because over-oxidation is highly thermodynamically favorable, and (iii) organic molecules generally contain many different types of C–H bonds, making it difficult to obtain a single functionalized product in these reactions. Current research in the Sanford group is working to address all of these challenges and to develop novel transition metal catalyzed methods for the site-, chemo-, regio-, and stereoselective functionalization of C–H bonds in the context of complex organic molecules. Our interests in this area include:
– Development of novel organic reactions and methods
– Application of these methods in the context of complex molecules
– Rational design of new catalysts informed by detailed mechanistic analysis
New Methods for the Oxidative Functionalization of Alkenes and Alkynes
A second area of research in the Sanford group involves developing new synthetic tools for the oxidative 1,1- and 1,2-difunctionalization of alkenes and alkynes with high levels of regio-, diastereo-, and enantiocontrol. Such transformations represent an attractive route to densely functionalized acyclic and heterocyclic products from simple and readily available starting materials. Our approach to these reactions has involved developing oxidative methods for the functionalization of Pd s-alkyl intermediates. The resulting PdII/IV pathways offer three highly attractive features relative to related (and much more common) PdII/0 processes. First, PdIV alkyls are generally not susceptible to ß-hydride elimination – a common decomposition pathway for their PdII analogues. Second, the PdIV intermediates participate in bond-constructions that are extremely challenging in the context of more traditional PdII/0 catalysis. Third, the catalysts and intermediates in PdII/IV chemistry are generally air and moisture stable, making these reactions convenient and practical for organic synthesis. Synthesis and Reactivity of High Oxidation State Late Transition Metal Complexes
A third research area in the Sanford lab involves studies on the synthesis and reactivity of unusual high oxidation state complexes of late transition metals (e.g., PdIII, PdIV, PtIII, NiIII, NiIV). Such complexes have been implicated as reactive intermediates in a variety of important catalytic transformations, including arene/alkane C–H bond functionalization, olefin aminohalogenation and aminoacetoxylation, and enyne cyclization/halogenation. However, organometallic compounds in these oxidation states (particularly those relevant to catalytic intermediates) remain rare, because their characteristic instability renders them difficult to observe, let alone isolate. Our goals are to rationally design ligands that will stabilize high oxidation state complexes and then study the reactivity of these species towards C–X bond forming reductive elimination as well as other fundamental organometallic transformations. This work will provide fundamental insights into the reactivity of high oxidation state group 10 metals that should ultimately find application in catalysis.
C–H Functionalization of Methane and Benzene
A final area of interest is the development of organometallic catalysts for the direct oxidation of simple alkanes and arenes (e.g., methane and benzene). This is a problem of critical global significance, since natural gas (which is >90% methane) is becoming an increasingly important precursor to carbon-containing chemicals and liquid fuels as petroleum supplies diminish. Current methods for methane conversion involve steam reforming to syngas followed by the Fisher Tropsch process (to access higher alkanes) or methanol synthesis; however, many major chemical companies have deemed this two-step sequence too costly and inefficient for long-term implementation. The direct conversion of benzene to phenol is another important industrial target, as the currently practiced phenol synthesis (the “cumene process”) is both energy intensive and low-yielding. As part of the NSF Center for Enabling New Technologies through Catalysis (CENTC), the Sanford group has been actively involved in catalyst development to address these important challenges. This work is a collaboration with Professors Jim Mayer (University of Washington), Karen Goldberg (University of Washington), Mike Heinekey (University of Washington), Bill Jones (University of Rochester), and Elon Ison (North Carolina State University).
Raymond and Beverly Sackler Prize in the Physical Sciences 2013
ASC Ipatieff Prize 2012
Classical High School Distinguished Alumni Award 2012
Moses Gomberg Collegiate Professor 2012
Paul Rylander Award from Organic Reactions Catalysis Society 2012
Tetrahedron Young Investigator Awards 2013 for Organic Synthesis 2012
Thieme IUPAC Prize in Synthetic Organic Chemistry 2012
American Association for the Advancement of Science Fellow 2011
Arthur F. Thurnau Professor 2011
MacArthur Fellowship 2011
ACS Award in Pure Chemistry 2010
John Dewey Award-LS&A 2010
National Fresenius Award 2010
BASF Catalysis Award 2009
ACS Arthur C. Cope Scholar Award 2008
Dupont Young Investigator Award 2007
Roche Excellence in Chemistry Award 2007
Abbott Young Investigator Award 2006
Alfred P. Sloane Research Fellow 2006
AstraZeneca Excellence in Chemistry Award 2006
Bristol-Myers-Squibb "Freedom to Discover" Award 2006
GlaxoSmithKline Chemistry Scholars Award 2006
National Science Foundation Career Award 2006
Presidential Early Career Awards for Scientists & Engineers(PECASE) 2006
Research Corporation Cottrell Scholar Award 2006
Amgen Young Investigator Award 2005
Boehringer Ingelheim New Investigator Award in Organic Synthesis 2005
Eli Lilly Grantee Award in Organic Chemistry 2005
Camille & Henry Dreyfus New Faculty Award 2003-2008
Deprez, N. R.; Sanford, M. S. “Synthetic and Mechanistic Studies of Pd-Catalyzed C–H Arylation with Diaryliodonium Salts: Evidence for a Bimetallic High Oxidation State Pd Intermediate,” J. Am. Chem. Soc. 2009, 131, 11234-11241.
Racowski, J. M.; Dick, A. R.; Sanford, M. S. “Detailed Study of C–O and C–C Bond-Forming Reductive Elimination from Stable C2N2O2 Palladium(IV) Complexes,” J. Am. Chem. Soc. 2009, 131, 10974-10983.
Hull, K. L.; Sanford, M. S. “Mechanism of Benzoquinone-Promoted Palladium-Catalyzed Oxidative Cross Coupling Reactions,” J. Am. Chem. Soc. 2009, 131, 9651-9653.
Ball, N. D.; Sanford, M. S. “Synthesis and Reactivity of a Mono-s-Aryl Palladium(IV) Fluoride Complex,” J. Am. Chem. Soc. 2009, 131, 3796-3797.
Kalyani, D.; Sanford, M. S. “Oxidatively Intercepting Heck Intermediates: Pd-Catalyzed 1,2- and 1,1-Arylhalogenation of Alkenes,” J. Am. Chem. Soc. 2008, 130, 2150-2151.
Hull, K. L.; Anani, W. Q.; Sanford, M. S. “Palladium-Catalyzed Fluorination of Carbon–Hydrogen Bonds,” J. Am. Chem. Soc. 2006, 128, 7134-7135.
Desai, L. V.; Hull, K. L.; Sanford, M. S. “Palladium-Catalyzed Oxygenation of Unactivated sp3 C–H Bonds,” J. Am. Chem. Soc. 2004, 126, 9542-9543.