Research Overview

 

The goal of my research group will be to creatively design approaches to solve problems of significant synthetic, material, environmental, and medicinal natures.  To optimally do so, my group will initially work on the design and development of new reactions that provide core structures of medicinal leads utilizing either novel access to reactive intermediates (Project 1) or unexplored cycloaddition components (Project 2).  Another project in the group will focus on the step-economical synthesis of analogues of medicinally significant molecules to probe and potentially improve the properties of the parent molecule (Project 3).  A final project in my group is the conversion of renewable resources into fuels and chemical feedstocks that are currently synthesized or isolated from nonrenewable sources (Project 4).  Collectively, these projects adequately illustrate the solutions to problems that my group will be involved with and their potential applications in society.

 

Project 1

Towards the goal of accessing novel reactive intermediates, it is proposed to use readily available alkynes to form cyano-carbenes.  This reaction thus converts one carbon atom of the terminal alkyne into a nitrile and the other into a carbene.  This cyano-carbene should react intramolecularly with a variety of functional groups to produce a diverse set of products by undergoing insertions, cycloadditions, 1,2-shifts, or cyclization reactions.  Due to this fundamentally unique and previously unexplored functional group transformation, it will be possible to construct molecules of significance in a more step-economical, efficient, and ideal fashion.  Specifically, this reaction constructs core structures that are present in compounds potentially used in the treatment or study of cancer, diabetes, and Alzheimer’s disease.

 

Project 2

Towards the goal of using new components in cycloadditions to form heterocycles, it is proposed to use novel compounds in organometallic reactions as heteroatom incorporating components.  Importantly, the novel heterocycles formed can be further functionalized for facile syntheses of pyrroles, furans, amino alcohols, and acyl silanes.  Furthermore, these products can be readily converted into additional structures via alkylations, cyclizations, cross-coupling, or oxidation state changes to produce structural motifs present in lead targets for the treatment of cancer, HIV, and influenza.

 

Project 3

Towards the goal of synthesizing medicinal leads for diseases and conditions with unaddressed and under-addressed treatments, it is proposed herein to synthesize analogues of one of the most potent neuroprotective compounds known.  Due to the significant increase in problems associated with neurological disorders, and the dearth of compounds available for the treatment of these disorders, neurotrophic compounds are a highly desirable class of compounds to fill this void.  The proposed synthesis of the compounds is designed to assemble the core structure rapidly and in such a manner that allows for facile access to a diverse set of analogues at a late stage.  The molecules will be designed to probe and improve the biological properties of this potential drug.

 

Project 4

Towards the goal of providing beneficial renewable energy sources, it is herein proposed to convert cellulose and glycerol to a molecule with potential to be used as a fuel additive for transportation or directly in a bioelectricity power plant.  As such, when used in a power plant employing carbon sequestration, this energy source would result in a net removal of carbon dioxide from the atmosphere.  Additionally, this project will access a feedstock chemical from glycerol instead of from petroleum sources from which it is normally derived.

 

 

REPRESENTATIVE PUBLICATIONS

1. Meza-Aviña, M. E.; Patel, M. K.; Lee, C. B.; Dietz, T. J.; Croatt, M. P. “Selective Formation of 1,5-Substituted Sulfonyl Triazoles using Acetylides and Sulfonyl Azides” Org. Lett. 2011, 13, 2984-2987.
   http://pubs.acs.org/doi/full/10.1021/ol200696q
2. Croatt, M. P.; Carreira, E. M. “Probing the Role of the Mycosamine C2’-OH on the Activity of Amphotericin B” Org. Lett. 2011, 13, 1390-1393.  http://pubs.acs.org/doi/full/10.1021/ol2000765
3. Croatt, M. P.; Wender, P. A. “The Diene Effect:  The Design, Development, and Mechanistic Investigation of Metal-Catalyzed Diene-yne, Diene-ene, and Diene-allene [2+2+1] Cycloaddition Reactions” Eur. J. Org. Chem. 2010, 19-32. (link)
4. Wender, P. A.; Croatt, M. P.; Kühn, B. “Rhodium(I)-Catalyzed [2+2], [2+2+2], and [2+2+2+2] Cycloadditions of Dienes or Alkynes with a Bis-ene” Organometallics 2009, 28, 5841-5844.  (link)
5. Wender, P. A.; Croatt, M. P.; Deschamps, N. M. “Higher Order Cycloadditions” Comprehensive Organometallic Chemistry III; Crabtree, R. H.; Mingos, D. M. P. Eds.; Elsevier:  Oxford, 2007, Vol. 10, pp 603-648.  (link)
6. Wender, P. A.; Croatt, M. P.; Deschamps, N. M. “Metal-Catalyzed [2+2+1] Cycloadditions of 1,3-Dienes, Allenes, and CO” Angew. Chem. Int. Ed. 2006, 45, 2459-2462.  (link)
7. Croatt, M. P.; Williams, T. J.; Wender, P. A. “Carbonyl(chloro)bis(triphenylphosphine) rhodium(I)” Encyclopedia of Reagents for Organic Synthesis John Wiley & Sons, Ltd., 2006, online.  (link)
8. Wender, P. A.; Croatt, M. P.; Witulski, B. “New Reactions and Step Economy:  The Total Synthesis of (±)-Salsolene Oxide Based on the Type II Transition Metal-Catalyzed Intramolecular [4+4] Cycloaddition” Tetrahedron 2006, 62, 7505-7511.  (link)
9. Wender, P. A.; Croatt, M. P.; Deschamps, N. M. “Rhodium(I)-Catalyzed [2+2+1] Cycloadditions of 1,3-Dienes, Alkenes, and CO” J. Am. Chem. Soc. 2004, 126, 5948-5949.  (link)
10. Croatt, M. P. “Design, Discovery, and Development of Novel Metal-Catalyzed Reactions and Their Use in Synthesis” Doctoral Thesis 2007, Stanford University.  (link)