Display Accessibility Tools

Accessibility Tools

Grayscale

Highlight Links

Change Contrast

Increase Text Size

Increase Letter Spacing

Readability Bar

Dyslexia Friendly Font

Increase Cursor Size

Robert E. Maleczka

Photo of 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.

Figure 1

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.

Figure 2.

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.

Figure 3

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.

Figure 4

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.

Figure 5

 

Contact / Webpage

Area(s) of Interest

Organic (Or)

Organometallic (Om)

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. 202287, 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 2022109, 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. Lett202123, 5724–5728.

“Phase behavior of selected condensed double-decker shaped silsesquioxane compounds” Vogelsang, D. F.; Maleczka, R. E., Jr.; Lee, A. Silicon 202113, 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. 201955, 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