David J. Michaelis
BS, cum laude, Brigham Young University (2005)
Ph.D., University of Wisconsin-Madison (2009)
NIH Postdoctoral Fellow, Stanford University (2010-2013)
The Michaelis Research Group takes a multidisciplinary approach to chemistry that enables advances not only at the interface of two fields, but also within strictly disciplinary research. This capacity derives from an acquired understanding of the scientific approach, methods, and techniques used in other disciplines to solve problems.
The Michaelis Lab intends to establish a research program that employs tools and techniques from other disciplines to solve difficult problems in organic synthesis and catalysis. With the experience and understanding gained through these early investigations, Michaelis researchers will be poised to answer important questions at the interface of chemistry and other fields. Michaelis researchers will have the opportunity to work at the interfaces of inorganic and organic synthesis, polymer science and catalysis, and structural biology and catalysis.
Polymer-Supported Nanoparticle Catalysts
The design and synthesis of metal-based nanostructured materials has emerged as a major research direction in several areas including optics and electronics, sensing, medicine, and catalysis. For these applications, the properties of a transition metal nanomaterial can be varied by changing the size (surface area), molecular structure, and shape of the nanoparticle itself. An alternative strategy for optimizing the physical, optical, or reactive properties of a nanoparticle is by designing and modifying the structure of the supporting matrix or surface-bound ligands. The Michaelis Lab Group seeks to design, synthesize, and utilize polymer-supported transition metal nanoparticles for catalytic applications where the nanoparticle reactivity and selectivity can be controlled by modification of the polymer support structure. Early published results from the Michaelis Lab have confirmed that the electronic structure of the supporting polymer can have a significant impact on catalytic activity in nitroarene reduction reactions. The main goals of this project are to 1) quantify the nature and strength of the polymer-nanoparticle interaction in order to rationally design nanoparticles with unique reactivity; and 2) use these nanoparticle catalysts to develop highly efficient organic transformations.
Electrophilic Catalysis with Heterobimetallic Complexes
The Michaelis Lab is broadly interested in new strategies to tune the reactivity and selectivity of transition metal catalysts. Incorporation of an electron-releasing or electron-withdrawing transition metal “ligand” into a bimetallic complex can greatly influence the reactivity of the active metal center. In this manner, enhanced electrophilic and nucleophilic catalysts can be generated through incorporation of an “inorganic ligand,” while maintaining supporting ligands capable of inducing the appropriate selectivity for the desired reaction. The main goal of this project is to understand and utilize heterobimetallic interactions to generate highly active electrophilic transition metal catalysts for organic synthesis. This project will seek to employ heterobimetallic catalysts for the development of olefin activation and C–H functionalization reactions.
α-Helical Peptide Scaffolds as Modular, Tunable, Enzyme-Like Catalysts for Multistep Synthesis
The enormous breadth of chemical reactions performed in biological systems can be attributed to nature’s ability to construct highly ordered arrangements of catalytic functional groups, or enzyme active sites. In addition, many organisms have evolved the ability to assemble polyketide synthases (PKSs), or multienzyme complexes that are capable of performing multistep synthesis in a linear fashion. Chemists have tried to mimic nature’s efficiency by constructing multifunctional catalysts or by designing multicomponent reactions or multi-catalyst systems. What is still lacking is a system that mimics nature’s ability to form structurally precise collections of functional groups (active sites) in a modular fashion that enables not only catalysis but also multistep synthesis. This project will investigate the use of short helical peptides to display catalytic functional groups in a stereocontrolled fashion to achieve enzyme-like catalysis. This template approach will provide a new strategy for catalyst design and optimization that takes advantage of substrate preorganization and proximity to improve catalytic activity. The helical scaffold will also make possible the design and construction of multifunctional catalysts capable of performing multistep synthetic processes.
Research interests include: Organic synthesis, catalysis, natural product total synthesis, inorganic synthesis, polymer chemistry, biocatalysis
30) Ence, C. C.; Nazari, S. H.; Rodriguez, M.; Kulka, S.; Gassaway, K.; Valdivia-Berroeta, G. A.; Michaelis, D. J. “2-Phosphinoimidazole-Derived Pd(I) and Pd(II) Dimers Enable a Bimetallic Approach to 1,3-Disubstituted Naphthalenes via Tandem Ketone Arylation and Cyclization.” Manuscript in preparation.
29) Martinez, E. E.; Jensen, C. A.; Larson, A. J. S.; Kenney, K. C.; Clark, K. J.; Nazari, S. H.; Valdivia-Berroeta, G. A.; Smith, S. J.; Ess, D. H.; Michaelis, D. J.; “Monosubstituted, Anionic Imidazolyl Ligands from N–H NHC Precursors and Their Activity in Pd-Catalyzed Cross-Coupling Reactions.” Adv. Synth. Catal. 2020, in Press.
28) Bahr, C. B.; Green, N. K.; Heki, L. K.; McMurray, E.; Tangen, I. C.; Valdivia-Berroeta, G. A.; Jackson, E. W.; Michaelis, D. J.; Johnson, J. A. “Heterogeneous layered structures for improved terahertz generation.” Opt. Lett. 2020, 45, 2054-2057.
27) Asay, S.; Graham, A.; Hollingsworth, S.; Barnes, B.; Oblad, R.; Michaelis, D. J.; Kenealey, J. “γ-tocotrienol and ɑ-tocopherol ether acetate enhance docetaxel activity in drug-resistant prostate cancer cells. Molecules 2020, 25, 398.
26) Valdivia-Berroeta, G. A.; Jackson, E. W.; Kenney, K. C.; Wayment, A. X.; Tangen, I. C.; Bahr, C. B.; Smith, S. J.; Michaelis, D. J.; Johnson, J. A. “Designing Non‐Centrosymmetric Molecular Crystals: Optimal Packing May Be Just One Carbon Away.” Adv. Funct. Mat. 2020, 30, 1904786.
25) Nazari, S. H.; Forson, K. G.; Martinez, E. E.; Hansen, N. J.; Gassaway, K. J.; Lyons, N. M.; Kenney, K. C.; Valdivia-Berroeta, G. A.; Smith, S. J.; Michaelis, D. J. “Boron-Templated Dimerization of Allylic Alcohols To Form Protected 1,3-Diols via Acid Catalysis.” Org. Lett. 2019, 21, 9589–9593.
24) Ence, C.; Walker, W. K.; Martinez, E.; Stokes, R. W.; Sarager, S.; Smith, S. J.; Michaelis, D. J. “Synthesis of Chiral Titanium-Containing Ligands for Enantioselective Heterobimetallic Catalysis.”Tetrahedron, 2019, 75, 3341–3347. Tetrahedron Young Investigator Award 2019, A Special Issue in Honor of Professor Ryan Shenvi.
23) Valdivia-Berroeta, G. A.; Hekia, L. K.; Jackson, E. W.; Tangen, I. C.; Bahr, C. B.; Smith, S. J.; Michaelis, d. J.; Johnson, J. A. “Terahertz generation and optical characteristics of (E)-2-(4-(dimethylamino)styryl)-1,1,3-trimethyl-1H-benzo[e]indol-3-ium iodide (P-BI).”Opt. Lett. 2019 44, 4279–4282.
22) Mohl, G.; Liddle, N.; Nygaard, J.; Dorius, A.; Lyons, N.; Hodek, J. Weber, J.; Michaelis, D. J.; Busath, D. D. “Novel Influenza Inhibitors Designed to Target PB1 Interactions with Host Importin RanBP5.” Antiviral Res. 2019, 164, 81–90.
21) Valdivia-Berroeta, G. A.; Heki, L. K.; McMurray, E. A.; Foote, L. A.; Nazari, H. S.; Serafin, L.; Smith, S. J.; Michaelis, D. J.; Johnson, J. A. “Alkynyl Pyridinium Crystals for THz Generation.” Adv. Opt. Mater. 2018, 6, 1800383.
20) Nazari, S. H.; Bourdeau, J. E.; Talley, M. R.; Valdivia-Berroeta, G. A.; Smith, S. J.; Michaelis, D. J. “Nickel-Catalyzed Suzuki Cross Couplings with Unprotected Allylic Alcohols Enabled by Bidentate NHC/Phosphine Ligands.” ACS Catal. 2018, 8, 86–89.
19) Kinghorn, M. J.; Valdivia-Berroeta, G. A.; Chantry, D. R.; Smith, M. S.; Ence, C. C.; Draper, S. R. E.; Duval, J. S.; Masino, B. M.; Cahoon, S. B.; Flansburg, R. R.; Conder, C. J.; Price, J. L.; Michaelis, D. J. “Proximity-Induced Reactivity and Selectivity with a Rationally Designed Bifunctional Helical Peptide Catalyst.” ACS Catal. 2017, 7, 7704–7708.
18) Tyler, J. H.; Patterson, R. H.; Nazari, S. H.; Udumula, V.; Smith, S. J.; Michaelis, D. J. Synthesis of N-Aryl “Hydroxylamines via Stalled Nitro Reductions with Soluble Ruthenium Nanoparticle Catalysts.” Tetrahedron Lett. 2017, 58,82–86.
17) Talley, M. R.; Stokes, R. W.; Walker, W. K.; Michaelis, D. J. “Electrophilic Activation of Alkynes for Enyne Cycloisomerization Reactions with In Situ Generated Early/Late Heterobimetallic Pt–Ti Catalysts.” Dalton Trans. 2016, 45, 9770–9773.
16) Udumula, V.; Nazari, S. H.; Burt, S. R.; Alfindee, M. N.; Michaelis, D. J. “Chemo- and Site-Selective Alkyl and Aryl Azide Reductions with Heterogeneous Nanoparticle Catalysts.” ACS Catal. 2016, 6, 4423–4427.
15) Udumula, V.; Tyler, J. H.; Davis, D. A.; Wang, H.; Linford, M. R.; Minson, P. S.; Michaelis, D. J. “A Dual Optimization Approach to Bimetallic Nanoparticle Catalysis: Impact of M1:M2 Ratio and Supporting Polymer Structure on Reactivity.” ACS Catal. 2015, 5, 3457–3462.
14) Walker, W. K.; Kay, B. M.; Michaelis, S. A.; Anderson, D. L.; Smith, S. J.; Ess, D. H.; Michaelis, D. J. “Origin of Fast Catalysis in Allylic Amination Reactions Catalyzed by Pd–Ti Heterobimetallic complexes.” J. Am. Chem. Soc. 2015, 137, 7371–7378.
13) Walker, W. K.; Anderson, D. L.; Stokes, R. W.; Smith, S. L.; Michaelis, D. J. “Allylic Aminations with Hindered Secondary Amine Nucleophiles Catalyzed by Heterobimetallic Ti–Pd Complexes.” Org. Lett. 2015, 17, 752–755.
Publications from Graduate and Postdoc Career
12) Williamson, K. S.; Michaelis, D. J.; Yoon, T. P. "Advances in the Chemistry of Oxaziridines." Chem. Rev. 2014, 114, 8016-8036.
11) Trost, B. M.; Michaelis, D. J.; Malhotra, S. “Total Synthesis of (–)-18-epi-peloruside A: An Alkyne Linchpin Strategy.” Org. Lett. 2013, 15, 5274–5277.
10) Trost, B. M.; Michaelis, D. J.; Truica, M. “Dinuclear Zinc–ProPhenol-Catalyzed Enantioselective α-Hydroxyacetate Aldol Reaction with Activated Ester Equivalents.” Org. Lett. 2013, 15, 4516–4519.
9) Trost, B. M.; Michaelis, D. J.; Charpentier, J.; Xu, J. “Palladium-catalyzed asymmetric allylic alkylation of carboxylic acid derivatives: N-acyloxazolinones as ester enolate equivalents.” Angew. Chem., Int. Ed. 2012, 54, 204–208.
8) Trost, B. M.; Lehr, K.; Michaelis, D. J.; Xu, J.; Buckl, A. K. “Palladium-catalyzed asymmetric allylic alkylation of 2-acylimidazoles as ester enolate equivalents.” J. Am. Chem. Soc. 2010, 132, 8915–8917.
7) Michaelis, D. J.; Williamson, K. S.; Yoon, T. P. “Oxaziridine-mediated enantioselective aminohydroxylation of styrenes catalyzed by copper(II) bis(oxazoline) complexes.” Tetrahedron 2009, 65, 5118–5124, invited symposium in print. PMID: 20161136 [PubMed]
6) Michaelis, D. J.; Dineen, T. “Ring-opening of aziridines with o-halophenyllithium reagents: synthesis of 2-substituted chiral indolines.” Tetrahedron Lett. 2009, 50, 1920–1923.
5) Michaelis, D. J.; Ischay, M. A.; Yoon, T. P. “Activation of N-sulfonyl oxaziridines using copper(II) catalysts: aminohydroxylations of styrenes and 1,3-dienes.” J. Am. Chem. Soc. 2008, 130, 6610–6615.
4) Michaelis, D. J.; Shaffer, C. J.; Yoon, T. P. “Copper(II)-catalyzed aminohydroxylation of olefins.” J. Am. Chem. Soc. 2007, 129, 1866–1867.
3) Parent, A. A.; Anderson, T. M.; Michaelis, D. J.; Jiang, G.; Savage, P. B.; Linford, M. R. “Direct ToF-SIMS analysis of organic halides and amines on TLC plates.” Applied Surface Science 2006, 252, 6746–6749.
2) Bronson, R. T.; Michaelis, D. J.; Lamb, R. D.; Husseini, G. A.; Farnsworth, P. B.; Linford, M. R.; Izatt, R. M.; Bradshaw, J. S.; Savage, P. B. “Construction of a surface bound metal ion sensor for Cadmium.” Org. Lett. 2005, 7, 1105–1108.
1) Ward, R. K.; Michaelis, D. J.; Murdoch, R.; Roberts, B.; Blixrud. “Widespread academic efforts address the scholarly communication crisis.” J. C&RL News 2003, 64(4), 382–383.