Mechanistic Investigations of Copper-catalyzed Azide/Alkyne Cycloadditions

EPA Grant Number: F13C10563
Title: Mechanistic Investigations of Copper-catalyzed Azide/Alkyne Cycloadditions
Investigators: Malik, Jamal
Institution: Scripps Research Institute
EPA Project Officer: Lee, Sonja
Project Period: August 1, 2014 through August 1, 2016
Project Amount: $84,000
RFA: STAR Graduate Fellowships (2013) RFA Text |  Recipients Lists
Research Category: Academic Fellowships , Fellowship - Chemistry

Objective:

CuAAC embodies the principles of green chemistry: it generates no byproducts, operates with a catalytic amount of an abundant earth metal (copper) and thrives in a variety of challenging conditions, including complex biological environments. Despite its widespread adoption, little is understood about the origin of the exceptional effectiveness of this reaction. This research project will employ real-time investigations of the mechanism of CuAAC, will provide insights into the fundamental interactions of coinage metals with carbon-carbon triple bonds and will apply this knowledge to creation of other environmentally benign reactions.

Approach:

This research uses heat flow reaction calorimetry as the primary method of reaction monitoring, which tracks the energy absorbed or emitted from reactions over time. These data will be manipulated to elucidate information about the reaction, including rate dependence on reactant concentrations, robustness of the catalyst and effect of electronic substitutions on acetylenes. Comparison of data between similar reactions will illustrate how much behavior of the catalyst is “universal” and how much is unique to the CuAAC.

Rationale:

Expected Results:

The kinetic information derived from these studies of the CuAAC is expected to add to current understanding of how organic molecules interact with common metals and improve the ease of use and performance of CuAAC for practitioners in other scientific fields. It should also provide insight into reactivity patterns that will allow creation of complementary green reactions that serve a wider base of scientists.

Potential to Further Environmental/Human Health Protection

Discovery of similar low-waste chemical transformations can significantly lower the carbon footprint from major industrial sources, broaden the possibilities for biological linkages and pave the way for greener polymers. The conversation about chemical synthesis can be changed from “Can we make these specific bonds at any cost?” to “With this powerful set of green reactions, what can we accomplish?”

Supplemental Keywords:

catalysis, earth-abundant metals, green chemistry

Relevant Websites:

Progress and Final Reports:

  • 2015
  • Final