Department of Chemistry

Robert W. Holman

Professor of Chemistry

Ph.D. Physical Organic Chemistry, University of Nebraska – 1988

Research area: Organic Chemistry, Organometallic Chemistry

Student experience required for research: Chem 111, Chem 112, enrolled in Chem 301

Student experience gained from research: Mechanistic methods, synthetic methods, NMR, air-sensitive techniques, computational chemistry, mass spectrometry

Ideal preparation for: Chemical industry, pharmaceuticals, medical research, preparation for graduate school in chemistry or for professional school

Research Description

1) Metalation in Hydrocarbon Solvents: The Mechanistic Aspects of ortho-Metalations

Directed ortho metalation (DoM) methods exist as an alternative to electrophilic aromatic substitution (EAS). Unlike EAS, DoM reactions are regiospecific, rarely undergo double addition, and can be performed in high yield under mild conditions.

Figure 1

Ethers are the predominant solvents utilized for DoM reactions because ethers are sufficiently able to deoligomerize alkyllithium reagents and also readily dissolve arene substrates. The disadvantages of ethers as solvents in these applications are, however, manifold. Ethers tend to react with reagents under various metalation conditions, have low flash points, are expensive to store and to dispose of, and care must be taken to remove both peroxides and water contaminants. As a result of these environmental and safety concerns, ether solvents are seldom considered for large-scale industrial synthetic applications. Our research centers upon the development of a new DoM reaction where the chemistry is conducted in hydrocarbon media. These solvents are inert towards alkyllithium reagents and peroxide and water contamination are not issues. Further, in industrial applications, hydrocarbon solvents do not present the environmental or safety problems that bulk quantities of ethers pose. Hydrocarbons are nonpolar and therefore cannot deoligomerize alkyllithium reagents, hence catalysts are typically required to promote the chemistry. The approach taken in this area of our research is to study a series of substrate/catalyst systems involving chlorotrimethylsilyl derivative formation as a function of time by 13C, 15N, 7Li and 17O NMR spectroscopic methods. Our goal is to develop an understanding of the mechanism for this chemistry and to be able to explain the role that parameters such as the nature of the substrate, the nature of the catalyst, the structure of complexes formed and the nature of the alkyllithium reagent have on the mechanism.

2) Assessments and Causes of the Cesium Effect.

Cesium reagents are well known catalysts for a wide variety of synthetic transformations and the generation of pharmaceutically useful intermediates. In many cases, cesium reagents are generally superior to their alkali metal counterparts with respect to reaction time and yield and most such conversions proceed under mild conditions. In particular, cesium bases have excelled at controlling reaction chemoselectivity and have been demonstrated to be highly compatible with a wide range of functional groups. This enhanced reactivity under mild conditions has been defined as the "cesium effect", and it is believed that this phenomenon stems from better solubilities of cesium bases and from the generation of highly reactive "naked anions." Although the striking efficiency of N-, O-, and S-alkylations has certainly not been in question in organic chemistry, the exact cause of the effect is still, to date, unknown. In order to shed light on such an important mechanistic problem, we plan to undertake a thorough investigation to explore this effect using 15N and 133Cs NMR with the goal being to understand the role that the cesium ion plays in this chemistry.

3) Chemistry: Novel Mechanistic Concepts and Synthetic Applications.

We wish to develop R-Ba-X analogs of classic Grignard reagents with the expectation that we can effect C-C bond formation in the construction of novel materials via a new methodology that may not have the limitations associated with the use of R-Mg-X reagents. The mechanistic evaluation of these organobarium reactions will be probed by 133Ba, 13C and 1H NMR spectroscopy. We will investigate these reactions in both ethereal and in hydrocarbon media with the use of catalysts.

Figure 2

Figure 3

Journal/Book Publications

“Podcasts for Pre-laboratory Student preparation in Organic Chemistry: A Recipe for Collaboration with University media Specialists,” Hallaq, Thomas, R.W. Holman,  Chem. Educator, in press, 2011.

“The Question-Guided Data-Driven Lecture: A New Approach Applied to the Presentation of the Principles Associated with SN2, SN1, E1, and E2 Reactions,” Jennifer M. Teixeira and R.W. Holman, Chem. Educator, 16, 1–3 1, 2011.

“The Question-Driven Laboratory Exercise: A New Pedagogy applied to a Green Modification of Grignard Formation/Reaction.”  Jessie Byers, Marilu Perez, J.M. Teixeira and R.W. Holman”  R.W. Holman and Jennifer Texiera,  Journal of Chemical Education, 87 (7), pp 714–716, 2010.

"A Simple Assignment Designed to Enhance Organic Chemistry Students Ability to Solve Synthesis Problems and Understand Mechanisms," R.W. Holman and J. Texiera, Journal of Chemical Education, 85,1,88-89, 2008.

"A recipe for an Academic-Industrial Partnership," R.W. Holman, Council on Undergraduate Research, CUR Quarterly, vol. XXVI, 2006.

"Metalations in Hydrocarbon Solvents; Media Effects on n-BuLi Reactivity," D.W. Slocum, A. Carroll, P. Dietzel, S. Eilerman, J.P. Culver, B. McClure, S. Brown and R. W. Holman, Tetrahedron Letters, 47, 6, 865-868, 2006.

"Strategic Applications of Named Reactions in Organic Synthesis: Background and Detailed Mechanisms," invited review, R.W. Holman, J. Chem. Ed. 82, 12, 1780-1783, 2005.

"Organic Chemistry as a Second Language: Translating the Basic Concepts," J. Chem. Ed.; 81, 1717, 2004.

"Structures and Properties of Gas-Phase Organic Ions: Halonium and Halenium Ions," an invited Book Chapter in the Encyclopedia of Mass Spectrometry, Pergamon Press, Oxford. Editor Nico Nibbering. 2004.

"Metalation in Hydrocarbon Solvents: Activation by Electron-Donating Groups," D. W. Slocum, P. Shelton, M. Timmons, J.P. Culver, B. D. Woosley, S. Brown, S. Dumbris, E. Mullins, R.W. Holman, Tetrahedron Letters, Submitted for publication, 2004.

"The Art of Writing Reasonable Reaction Mechanisms," J. Chem. Ed. Reviews, 80, 1259, 2003.

"Metalation in Hydrocarbon Solvents: The Mechanistic Aspects of Substrate Promoted ortho-Metalations," C. Harrison, G. Jackson, R. LaMastus, P. Shelton, A. Walstrom, J.M. Wilcox, D.W. Slocum, R.W. Holman, Tetrahedron, 59, 8275-8284, 2003.

"An Investigation of Gaseous a-Halogenated Carbocations versus Halonium, Halenium, and Allylhalonium Ions," R.W. Holman, J. Davis, A. Groves, M. McCombs, G. Jackson, S. Sullivan, M.L. Gross, Aust. J. Chem. 56 (5), 437, 2003.

"Foundations of Organic Chemistry: Worked Examples," R.W. Holman, J. Chem. Ed. Reviews, 80 (2), 149-150, 2003.

"Organic Chemistry, CD," R.W. Holman, J. Chem. Ed. Reviews, 78 (12), 1603-1604, 2001.

"Cyclopropane as a Propagating Reagent in Gas-Phase Radical Cation Oligomerization," R. W. Holman, Atkins, B., D. Giblin, D. Rempel, M. L. Gross, Int. J. Mass Spectrom., 210/211, 569-584, 2001.

"On Bicyclobutonium Ion versus Cyclopropylcarbinyl Cation Chemistry: The Cycloaddition Reaction with Ethylene in the Dilute Gas Phase," R.W. Holman, J. Plocica, L. Blair, D. Giblin, M.L. Gross, J. Phys. Org. Chem., 14, 17-24, 2001.

"Gas-Phase Electrophilic Aromatic Substitution of Electron-Rich and Electron-Deficient Aromatic Compounds"; R.W. Holman, T. Eary, E. Whittle, M.L. Gross J. Chem. Soc. Perkin Trans. II, 2187, 1998.


IDAHO STATE UNIVERSITY

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