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Croatt Research Group

Recent Projects

Reactions of Azides and Alkynes

My group is interested in exploring novel reactions of azides and alkynes. Traditionally, these two components have been assembled to form 1,4-substituted triazoles, one of the “click reactions.” Complementary to this work, our group has determined a method to react alkynes and sulfonyl-azides to form 1,5-sulfonyl-triazoles. The umpolung reactivity was also explored wherein an electrophilic alkyne was reacted with azide nucleophiles to form and react as cyanocarbenes after extrusion of dinitrogen. Funding for this project was provided by the American Chemical Society Petroleum Research Fund in the form of a Doctoral New Investigator (52488-DNI1) and is currently provided by the National Science Foundation in the form of a CAREER grant (1351883). This support is gratefully acknowledged. 

Representative Publications:

“Formation and in situ reactions of hypervalent iodonium alkynyl triflates to form cyanocarbenes” 
I. F. Dempsey Hyatt, Daniel J. Nasrallah, Michael A. Maxwell, A. Christina F. Hairston, Manahil M. Abdalhameed, and Mitchell P. Croatt
Chemical Communications 2015, 51, 5287-5289.
(Special Issue for 2015 Emerging Investigators)

“Exploring the reactivity of 1,5-disubstituted sulfonyl-triazoles: Thermolysis and Rh(II)-catalyzed synthesis of α-sulfonyl nitriles” 
Maria Elena Meza-Aviña, Mudita Kishor Patel, and Mitchell P. Croatt
Tetrahedron 201369, 7840-7846.
(Special Issue in Honor of Professor Wender)

"Reactions of Hypervalent Iodonium-Alkynyl Triflates with Azides: New Mechanistic Approach for the Generation of Cyanocarbenes" 
I. F. Dempsey Hyatt, Mitchell P. Croatt
(Featured with the Front Cover Graphic of that issue of Angew. Chem., Int. Ed. and Highlighted in Angew. Chem. Int. Ed. 201251, 12169-12171.)

"Selective Formation of 1,5-Substituted Sulfonyl Triazoles Using Acetylides and Sulfonyl Azides"
Maria Elena Meza-Aviña, Mudita Kishor Patel, Cylivia B. Lee, Thomas J. Dietz, Mitchell P. Croatt
Organic Letters 2011, 13, 2984-2987; 

(Highlighted in SYNFACTS 2011, 9, 1005) 

“Alkynes and Azides:  Not Just for Click Reactions”
I. F. Dempsey Hyatt, Maria Elena Meza-Aviña, and Mitchell P. Croatt
Synlett 2012, 23, 2869-2874.
(Invited SYNPACTS article)

Synthesis and Analysis of Isocarbacyclin Analogs

Isocarbacyclin, an analog of prostacyclin, has been found to be a potent neuroprotective agent. In particular, this compound has been studied in cells and animal models for neural protection from stroke. My group has designed a step-economical synthesis of isocarbacyclin that is conducive to the facile synthesis of analogs where the diversity of the compounds is installed at the final step of the synthesis. This allows for the largest amount of analogs to be synthesized in the fewest number of steps. Using three transition metal catalyzed reactions for the final three steps of the synthesis, a dienyl ester (available in only 4 steps) is converted to the isocarbacyclin analogs. Specifically, a palladium(0) catalyst enables a decarboxylation with concomitant allylic rearrangement, a rhodium(I) catalyst enables a diene-ene [2+2+1] cycloaddition to take place, and a ruthenium(II) catalyst diversifies the structure through a cross-metathesis reaction with various alkene side-chains. These compounds are being explored as neuroprotective compounds and the palladium-catalyzed step is being explored for the synthesis of other compounds that benefit from the dienylation reaction. Funding for this project has been provided by the North Carolina Biotechnology Center in the form of a Biotechnology Research Grant (2014-BRG-1205).

Representative Publications: 

“Sequential Pd(0)-, Rh(I)-, and Ru(II)-catalyzed Reactions in a Nine-step Synthesis of Clinprost”
Emma E. Nagy, I. F. Dempsey Hyatt, Kristen E. Gettys, Shawn T. Yeazell, Stephen K. Frempong Jr., and Mitchell P. Croatt
Organic Letters 201315, 586-589.

Novel Ligands for GPCRs

This is a collaborative project where new ligands for GPCRs are designed and optimized using the molecular modeling of the group of Dr. Patricia Reggio at UNCG. Targeted libraries of compounds are then synthesized in my group. The syntheses are designed to be convergent so that a large number of analogs can be synthesized in a minimal number of steps. The compounds are then sent to Temple University where the groupof Dr. Mary Abood determines their ability to agonize or antagonize the different GPCRs. This information is then used to modify the modeling data which enables the iterative optimization cycle to continue. Funding for this project has been provided by the National Institute of Health in the form of R01 (DA023204) and an R21 (NS077347) grants. This support is gratefully acknowledged. 

Selected Publications: 

“Identification of the GPR55 Antagonist Binding Site Using a Novel Set of High-Potency GPR55 Selective Ligands”
Evangelia Kotsikorou, Haleli Sharir, Derek M Shore, Dow P. Hurst, Diane L. Lynch, Karla E. Madrigal, Susanne Heynen-Genel, Loribelle B. Milan, Thomas D.Y. Chung, Herbert H. Seltzman, Yushi Bai, Marc G. Caron, Lawrence S. Barak, Mitchell P Croatt, Mary E Abood, and Patricia H. Reggio
Biochemistry 201352, 9456-9469.

Synthesis of a Novel Biofuel

Using cellulose and bio-ethanol as starting materials, my group is exploring some of the acid-catalyzed pathways to combine these two renewable energy sources to access a novel biofuel that combines the beneficial properties of each component in a synergistic fashion. In particular, we are exploring some of the furanic products in attempts to make them more attractive, energy-dense biofuels. 

Selected Publications: 
Coming Soon!