Croatt Research Group
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.
“Formation and in situ reactions of hypervalent iodonium alkynyl triflates to form cyanocarbenes”
“Exploring the reactivity of 1,5-disubstituted sulfonyl-triazoles: Thermolysis and Rh(II)-catalyzed synthesis of α-sulfonyl nitriles”
"Reactions of Hypervalent Iodonium-Alkynyl Triflates with Azides: New Mechanistic Approach for the Generation of Cyanocarbenes"
"Selective Formation of 1,5-Substituted Sulfonyl Triazoles Using Acetylides and Sulfonyl Azides"
“Alkynes and Azides: Not Just for Click Reactions”
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).
“Sequential Pd(0)-, Rh(I)-, and Ru(II)-catalyzed Reactions in a Nine-step Synthesis of Clinprost”
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.
“Identification of the GPR55 Antagonist Binding Site Using a Novel Set of High-Potency GPR55 Selective Ligands”
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.