Robert E. Maleczka

Research

Synthetic Organic Chemistry

(Research Description PDF)

Our group is interested in a) green chemistry, b) the invention of new reactions and strategies in organic synthesis, and c) target synthesis of molecules with interesting properties ranging from biologically important natural products to nanomaterials.

Green Chemistry: Central to our research is the development of efficient and environmentally benign reactions and strategies. The Pharmaceutical Roundtable of the American Chemical Society’s Green Chemistry Institute deemed cross-couplings that avoid haloaromatics as their top aspirational reaction. In collaboration with Professor Mitch Smith, we are inventing such reactions. Specifically, we are using catalytic C–H activation/borylation, often combined with subsequent chemical events, to generate pharmaceutically relevant building blocks for organic synthesis and the late stage functionalization of drugs and drug candidates.

Invention of New Reactions: The principles of green chemistry also motivate us to create new synthetic methods. Within our catalytic borylation program, an example is our recently disclosed use of ion-pairing, where the alkyl groups of the cation create a steric shield that facilitates previously unheard of levels of para selectivity.

We are also focusing on the employment of organosilanes as both reagents and substrates in chemical transformations ranging from Wittig rearrangements to new approaches to double-decker silsesquioxanes (DDSQ’s) for materials applications.

Since their discovery more than 70 years ago, Wittig rearrangements have evolved into powerful tools for the isomerization of a-metalated ethers into alkoxides. Relative to the [2,3]- and [1,2]-shifts, [1,4]-Wittig rearrangements are unique in their ability to generate stereodefined enolates. In addition, [1,4]-Wittig rearrangements have the potential to transfer chirality and stereoselectively form adjacent chiral centers. As such, we continue to study these mechanistically fascinating and synthetically intriguing rearrangements.

We have also teamed up with Chemical Engineering and Materials Science Professor Andre Lee, to apply our synthetic expertise to another remarkable class of compounds, namely silsesquioxanes. These caged structures have garnered significant attention over their ability to meet the demands of medical, aerospace and materials industries. This is due to the well-defined spatial dimensions, the presence of seven inert peripheral organic moieties to accommodate solubility and processability, and one polymerizable reactive organic group.

Like our other projects, we approach the synthesis of silsesquioxane through the lens of green chemistry. An example of this can be seen in our development of the first direct synthetic route leading to asymmetrically functionalized DDSQ compounds. By way of our route over 50% of the starting DDSQ tetraol that could have otherwise contributed toward the synthesis of unwanted side products is recovered with a high purity and can be used in another cycle of synthesis. Efforts to use these compounds as nano-linkers to two different block copolymers are underway in our lab.

Target Synthesis: A unifying thesis behind all of our methodological and mechanistic studies is that the chemistry to emerge from such studies should be applicable to real synthetic problems. We view target synthesis as the best proof of this concept. For example, as part of our green chemistry program, we look to make TMC-95A and autolytimycin by the strategic application of our own synthetic methods.

 

Contact / Webpage

Area(s) of Interest

Organic (Or)

Selected Publications

“Steric shielding effects induced by intramolecular C–H•••O hydrogen bonding: Remote borylation directed by Bpin groups” Montero Bastidas, J. R.; Chhabra, A.; Feng, Y.; Oleskey, T. J.; Smith, M. R., III; Maleczka, R. E.; Jr. ACS Catal. 2022, 12, 2694–2705.

“Merging Iridium-Catalyzed C–H Borylations with Palladium-Catalyzed Cross-Couplings using Triorganoindium Reagents” Jayasundara, C. R. K.; Gil-Negrete, J.-M.; Montero Bastidas, J. R.; Chhabra, A.; Martínez, M. M.; Sestelo, J. P.; Smith, M. R., III; Maleczka, R. E.; Jr. J. Org. Chem. 2022, 87, 751–759.

“Amide Directed Iridium C(sp3)–H Borylation Catalysis with High N-Methyl Selectivity” Dannatt, J. E.; Yadav, A.; Smith, M. R., III; Maleczka, R. E.; Jr. Tetrahedron 2022, 109, 132578.

“Silylcyclopropanes by Selective [1,4]-Wittig Rearrangement of 4-Silyl-5,6-Dihydropyrans” Mori-Quiroz, L. M.; Maloba, E. W.; Maleczka, R. E.; Jr. Org. Lett. 2021, 23, 5724–5728.

“Phase behavior of selected condensed double-decker shaped silsesquioxane compounds” Vogelsang, D. F.; Maleczka, R. E., Jr.; Lee, A. Silicon 2021, 13, published on-line 11/4/2021.

One-Pot Iridium Catalyzed C–H Borylation/ Sonogashira Cross-Coupling: Access to Borylated Aryl Alkynes, Chotana, G. A.; Montero Bastida, J. R.; Miller, S. L.; Smith, M. R., III; Maleczka, R. E., Jr., Molecules 2020, 25, 1754–1766.

Para-Selective, Iridium-Catalyzed C–H Borylations of Sulfated Phenols, Benzyl Alcohols, and Anilines Directed by Ion-Pair Electrostatic Interactions, M. Bastida, J. R.; Oleskey, T. J.; Miller, S. L.; Smith, M. R., III; Maleczka, R. E., Jr., J. Am. Chem. Soc. 2019, 141, 15483–15487.

C–H Borylation Catalysts that Distinguish Between Similarly Sized Substituents Like Fluorine and Hydrogen, Miller, S. L.; Chotana, G. A.; Fritz, J. A.; Chattopadhyay, B.; Maleczka, R. E., Jr.; Smith, M. R., III, Org. Lett. 2019, 21, 6388–6392.

A General Diversity Oriented Synthesis of Asymmetric Double-Decker Shaped Silsesquioxanes, Barry, B.-D.; Dannatt, J. E.; King, A. K.; Lee, A.; Maleczka, R. E., Jr., Chem. Commun. 2019, 55, 8623–8626.

Phase Behavior of cis–trans Mixtures of Double-Decker Shaped Silsesquioxanes for Processability Enhancement, Vogelsang, D. F.; Dannatt, J. E.; Shoen, B. W.; Maleczka, R. E., Jr.; Lee, A., ACS Appl. Nano Mater. 2019, 2, 1223–1231.

Predictive Liquid Chromatography Separation for Mixtures of Functionalized Double-decker Shaped Silsesquioxanes Based on HPLC Chromatograms, Vogelsang, D. F.; Maleczka, R. E., Jr.; Lee, A., Ind. Eng. Chem. Res. 2019, 58, 403–410.

HPLC Characterization of cis and trans Mixtures of Double-Decker Shaped Silsesquioxanes, Vogelsang, D. F.; Maleczka, R. E., Jr.; Lee, A., Silicon 2019, 11, 5–13.

CV

B.S., 1984, Univ. of Illinois at Urbana-Champaign

Abbott Labs, 1984-1987

Ph.D., 1992, The Ohio State Univ.

Postdoctoral Fellow, 1992-1995, American Cancer Society Univ. of Pennsylvania

Awards

Year	Award	Organization
2021	Elected Fellow of the American Association for the Advancement of Science (AAAS)
2018	Named Honored Professor of ‘Overseas Expertise Introduction Center for Green Pharmaceuticals Discipline Innovation (111 Center)’	Zhejiang University of Technology, China
2018	Hess Lecturer	Illinois Wesleyan University
2014	Elected Fellow of the American Chemical Society (ACS)
2013	Meritorious Faculty Award by the College of Natural Science Alumni Association
2013	Merck Technology Collaboration Award	Merck
2008	US EPA’s Presidential Green Chemistry Challenge Award
2006	Astellas USA Foundation Faculty Award	Astellas USA Foundation
2003 - 2004	Smith First Edition Board of Advisors	McGraw Hill
2001 - 2005	Yamanouchi USA Foundation Faculty Award	Yamanouchi USA Foundation
2001	Teacher-Scholar Award	College of Natural Science
2000	Novartis Lecturer	Yale University
2000 - 2003	NSF Career Award	National Science Foundation
2000	Meritorious Faculty Research Award	Michigan State University
2000	Junior Faculty Award	Sigma Xi Honor Society (Michigan State University)
1998 - 2001	NIH First Award	National Institutes of Health
1998	MSU Chapter Mentor of the Year	National Organization for the Professional Advancement of Black Chemists and Chemical Engineers
1998	MSU Senior Class Council Outstanding Faculty Award Nominee	Michigan State University (Senior Class Council)
1993 - 1995	Postdoctoral Fellow	American Cancer Society
1993	American Cancer Society Post-Doctoral Fellow	University of Pennsylvania
1987 - 1992	Graduate Research Associate	The Ohio State University
1984 - 1987	Research Assistantship	Abbott Laboratories
1984	Bachelor of Science	University of Illinois, Urbana-Champaign
1983 - 1984	Undergraduate Research	University of Illinois, Urbana-Champaign
1980 - 1982	Air Force ROTC Scholarship	Air Force ROTC
	Dean's List	University of Illinois, Urbana-Champaign