Chemistry - Faculty - Rosenstein

Ian Rosenstein, Organic Chemistry

Associate Professor and Chair

Office: SCCT 1074
Phone: 315-859-4730
Email: irosenst@hamilton.edu

At Hamilton since 1994

EDUCATION

B.S. Massachusetts Institute of Technology
Ph.D. Duke University

RESEARCH

Two themes are central to current research projects in Prof. Rosenstein’s lab: addition reactions of carbon centered radicals and the chemistry of small ring systems. Of particular interest is the chemistry of the cyclopropylcarbinyl radical. Two projects in the lab combine these two interests, focusing on the ring opening of the cyclopropylcarbinyl radical. One of these projects is a mechanistic study while the second aims to utilize this reaction in synthetic transformations. Specific projects include:

1. Does the Cyclopropylcarbinyl Radical Ring Opening Reaction Occur through a Dipolar Transition State.

The cyclopropylcarbinyl radical ring opening reaction is the most frequently applied example of what is known as a free radical clock. Radical clocks are fast reactions with precisely measured rates that can be used to determine the rates of other radical process through competition kinetics studies. It is important for chemists to develop a full understanding of the details of the mechanism of the cyclopropylcarbinyl radical ring opening reaction because such an understanding will allow for the development of faster and more diverse radical clocks. From studies of the ring opening of differentially substituted cyclopropylcarbinyl radicals, empirical observations are consistent with the development of dipolar character in the transition state of the ring opening but little direct exists to support this hypothesis.

Specifically, our goal is to synthesize a series of precursors to aryl substituted cyclopropylcarbinyl radicals, varying the electronic nature of the substituents on the aromatic ring from electron-rich to electron-poor. If the transition state has dipolar character, the rate of the reaction should increase as the aromatic substituent becomes more electron-poor. The exact nature of this variation can be examined using the Hammett equation to provide direct quantitative evidence to support or disprove the participation of a dipolar transition state.

2. Stereoselective Construction of Multicyclic Ring Structures Using the Radical Induced Transformation of Vinylcyclopropanes to Vinylcyclopentanes

Cyclopentane containing bi- and tricyclic frameworks are common in biologically important natural products but methods for the direct synthesis of cyclopentanes are fairly limited. In this project, we are examining the use of the radical mediated conversion of vinylcyclopropanes to vinylcyclopentanes, a well explored reaction for monocyclic systems, for the synthesis of bi- and tricyclic cyclopentane containing compounds. Of particular interest is developing methodology for using chiral auxiliaries to control the stereochemical outcomes of these reactions. An example reaction sequence is shown below.

3. Chiral Auxiliary-Mediated, Stereoselective Synthesis of Bicyclic Cyclopropanes

We are working to develop methods for the stereoselective synthesis of the bicyclic cyclopropanes that are needed as precursors for the radical cascade processes described above. Specifically, we plan to carry out these reactions using ylide reagents that are substituted with the same chiral auxiliaries that we will use to control the stereochemistry of the radical reaction.

4. Synthesis of Selectively Protiated Propylene Oxide

Our research group is involved in a collaborative project with Prof. Camille Jones to study the dynamics of the movement of propylene oxide inside a clathrate hydrate cage. In order for Prof. Jones’ group to carry out the dynamic studies using inelastic neutron scattering, our group is synthesizing the three possible selectively protiated propylene oxide molecules shown below.

RELEVANT PUBLICATIONS

Rosenstein, I. J. “Radical Allylation and Vinylation Using Tin Reagents”, Organic Reactions, invited manuscript in preparation

Rosenstein, I. J. “A Literature Exercise Using SciFinder Scholar for the Sophomore Organic Course”, J. Chem. Ed., 2005, 82, 652.

Rosenstein, I. J. “Bis((1R,2S,5R)-menthyl)(phenyl)tin hydride”, Electronic Encyclopedia of Reagents in Organic Synthesis, http://www3.interscience.wiley.com/cgi-bin/mrwhome/104554785/HOME, 2005.

Rosenstein, I.J. "Radical Fragmentation Reactions" in Radicals in Organic Synthesis, Vol. 1; Renaud, P., Sibi, M.P., Eds.; Wiley-VCH: Weinheim, 2001.

Rosenstein, I. J.; Tynan, T. A.* "Imine Derivatives of Fumaraldehyde From Oxidation of a B-Aziridinyl Alcohol" Synthetic Communications 30 (2000) 1447-55.

Rosenstein, I.J.; Tynan, T.A.* "Chiral Auxiliary Mediated Stereoselective Allylation of Electron Deficient Radicals" Tetrahedron Lett. 39 (1998) 8429.

RECENT PRESENTATIONS

Stroud, A. M.*; Rosenstein, Ian J. “Ester Chiral Auxiliaries for the Control of Stereochemistry in Addition Reactions of Tertiary, Electrophilic Radicals” 225th National Meeting of the American Chemical Society, New Orleans, LA, March 2003.

Elgren, T. E.; Rosenstein, I. J.; Kinnel, R. B.; Subramaniam, R.; Palmitesso, R. J.* “An Integrated Context for Introducing Research Methods in Chemistry” 225th National Meeting of the American Chemical Society, New Orleans, LA, March 2003.

Rosenstein, I. J.; Bennett, A.*; Chicaiza, H.*; Lin, A.*; Markeson, G.*; McSurdy, G.*; Stewart, S.*; Stroud, A.* “Development of Novel Manganese-Mediated Radical Addition Reactions of Electron-Deficient Radicals” Gordon Research Conference on Free Radical Reactions, Holderness, NH, July 2003.

Rosenstein, I. J.; Elgren, T. E. “Miracles, Disasters and Everyday Chemistry” 226th National Meeting of the American Chemical Society, New York, NY, September 2003.

Rosenstein, I. J.; Chicaiza, H. P.* “Synthesis of Radical Precursors for the Study of the Cyclopropylcarbinyl Radical Ring Opening Reaction” 227th National Meeting of the American Chemical Society, Anaheim, CA, March 2004.

Rosenstein, I. J.; Vaickus, L. J.* “Intermolecular Free Radical Addition Reactions of alpha-Nitro Esters and Ketones and beta-Keto Esters” 39th National Organic Symposium, Salt Lake City, UT, June 2005.

Rosenstein, I. J.; Vaickus, L. J.* “Free Radical Addition Reactions of a-Nitro Carbonyl Compounds” Gordon Research Conference on Free Radical Reactions, Holderness, NH, July 2005.

Griffith, D.*; Lehman, H. K.; Rosenstein, I. J. “Synthesis of (4-Hydroxyphenyl)acetaldehyde and Inhibitors of Tyramine β-Hydroxylase” 40th National Organic Symposium, Durham, NC, June 2007.

Griffith, D.*; Rosenstein, I. J. “Studies Towards Reagent-Controlled Asymmetric Cyclopropanations of Michael Acceptors” 40th National Organic Symposium, Durham, NC, June 2007.

McKee, S.*; Nizialek, G.*; Jones, C. Y.; Rosenstein, I. J. “Synthesis of Selectively Deuterated Propylene Oxide for Use as a Probe of Dynamics Within a Clathrate Hydrate Cage” 40th National Organic Symposium, Durham, NC, June 2007.

Parkhurst, R. R.*; Rosenstein, I. J. “Investigation of Novel Methods for Stereoselective Synthesis Involving Radical Translocation” 40th National Organic Symposium, Durham, NC, June 2007.

Johnson, K. P.*; Brewer, K. S.; Kinnel, R. B.; Rosenstein, I. J.; Elgren, T. E. “Porphyrin Chemistry: An Integrated Investigative Advanced Laboratory Course” 235th American Chemical Society National Meeting, New Orleans, LA, April 2008.

* Student Authors