Research Interests:
I have been retired for 10 years. I have had the pleasure of working with many PhDs, postdocs, and exceptional undergraduates at the University of Chicago. We focused on the synthesis and examination of new ring systems specifically designed as probes into the effects of molecular geometry on bonding, reactivity, strain, etc. In the course of our work we were the first to synthesize cubane, pentaprismane, [2.2.2]propellane, the [n.2.2.2]paddlanes, and many, many other highly strained, so-called unnatural compounds (Mother Nature can’t do the job, or perhaps she’s just not interested). These systems gave us special opportunities to study the behavior of exceptionally strained molecules vis-a-vis their propensity for rearrangement and reaction.
Cubane is the most highly strained, kinetically stable ring system available in multi-gram quantities. We used it as the precursor of yet more highly strained compounds, including 1(9)-homocubene (the most highly twisted olefin), cubene, (the most highly pyramidalized olefin), and such intriguing species as 1,4-dehydrocubane, cubyl cation (the "least likely" cation), and the cubylcarbinyl radical (the fastest rearranging saturated radical). These have record properties and as such have proven to be of fundamental importance to understanding the boundaries of bonding between carbons.
As the geometric requirements of such compounds are far from ordinary, tactical synthesis is an exceptional challenge. Much of our work, therefore, was on the development and application of new synthesis methods and techniques. A few examples: intrafacial nitration; P2O5/CF3SO3H for condensations; amido- and di-amido Grignards; substitutions on aliphatics via carboxamide activation for direct metalation, transmetalation, reverse transmetalation.You can find in the literature reference to the power of these methods even far beyond strained ring chemistry.
Cubanes and other unnatural products offer many and diverse applications. Octanitrocubane, first prepared in my labs by an extraordinary combinations of techniques, is remarkably stable. But it is also probably the most powerful known nonnuclear explosive. I am comfortably sure it will never be used – it is far too expensive to make. I can note happily that my hypothesis of pharmaceutical utility made years ago has recently been validated: cubane has been shown to be a suitable bioisostere to replace the benzene part of widely different agrochemicals and pharmaceuticals. A few examples: diflucuburon consistently outperforms diflubenzuron against the rust-red flour beetle; cubocaine is as potent against pain as benzocaine.
Selected References
Validating Eaton’s Hypothesis: Cubane as a Benzene Bioisostere, J. Tsanaktsidis (an ex-postdoc), G. P. Savage, C. M Williams et al., Angew. Chemie, Int. Ed. 2016, 55.
Cubane: Starting Material for the 1990s and the New Century. Angew. Chemie Int. Ed. Engl. 1992, 31, 1421-1436
BuMgNiPr2: A New Base for Stoichiometric, Position-Selective Deprotonation of Cyclopropane Carboxamides and Other Weak CH Acids, Angew. Chemie Int. Ed. Engl., 2002, 41, 2169-2171.
Hepta- and Octanitrocubane, Angew. Chemie. Int. Ed. Engl. 39, 401-404 (2000).
Building with Cubane-1,4-diyl. Synthesis of Aryl Substituted Cubanes, p-[n]Cubyls, and Cubane Separated Bis-Arenes. J. Am. Chem. Soc., 1999, 121, 4111.
Reverse Transmetalation: A Strategy for Obtaining Certain Otherwise Difficultly Accessible Organometallics J. Am. Chem. Soc., 1987, 109, 948