Adapting synthesis and manufacturing technology is crucial for keeping up with the needs and demands occurring in society. Since the exigency for environmentally benign technologies is ever growing, the focus should be directed on finding more efficient, nontoxic routes to the consumable products that we need in our day-to-day lives. Palladium complexes have proven to be excellent catalysts for C-C bond formation under a variety of conditions, making it only reasonable that the area of Pd-catalyzed organic reactions is exploited to find these routes.
We have presented the idea that commercially available surfactant molecules are efficient additives to enhance Pd-catalyzed Sonogashira coupling reactions under mild aqueous conditions. Surfactants such as SDS and CTAB give high to quantitative coupling yields for aryl iodide and activated aryl bromide substrates with aromatic or aliphatic terminal alkynes. Since aryl bromide reactions proceed better without addition of the auxiliary reagent CuI, it would be beneficial to adapt and modify the representative surfactant conditions to enhance coupling yield. Substantial enhancement to reaction conditions is expected to originate from use of a more reactive Pd-catalyst as well as modification of the surfactant molecule. Both the structures of SDS and CTAB can be easily modified from biosourced reagents (i.e. aliphatic alcohols and bioengineered molecules from E. coli) to assess what structural changes to the existing surfactant molecule improves reaction yields and conditions.
Additionally, nontraditional surfactants, such as sodium cholate, can also have an influence on coupling reactions. Modification of methyl cholate with a phosphine moiety proved to be an effective ligand in Pd-catalyzed reactions in water. The cholate-phosphine ligand produced a heterogeneous Pd complex that was an efficient catalyst for Heck coupling of nonpolar substrates in water. Addition of the phosphine moiety increased the hydrophobic nature of cholate enough that the resultant Pd-complex was not soluble in water. However, the complex provided enhanced reactivity due to a hydrophobic effect, creating a localized high concentration of organic reagents around the metal center. Modification to the cholate molecule (e.g. multiple carboxylic acid groups) may be a way to enhance solubility in water or complex aggregation into cholate-like micelles of the resultant Pd-complex, allowing improvement in coupling yields, and possible access to less activated aryl halides.
Lastly, palladium complexes with NHC ligands proved to be active alkoxycarbonylation catalysts for a variety of terminal olefins. These complexes were active for high to quantitative conversion of substrate without exclusion of air or water, while not needing additional auxiliary reagents such as acids. Moreover, they have significant advantages over the analogous Pd-phosphine system which is limited by the phosphine ligand sensitivity to oxygen and poor catalytic activity without strongly acidic activating additives. The initial results suggest that modification to the NHC ligands by increasing steric bulk might enhance product selectivity. Also, reaction analyses indicate that one NHC is lost in situ to generate
the active catalytic species; therefore improved catalytic activity may also be achieved via dimeric Pd-NHC complexes that provide a 1:1 Pd-NHC composition. Together, these research projects highlight three important areas of green chemistry – improving catalysis conditions, using greener solvents and expanding transformations of bioderrived feedstocks. Each area provides a foundation for further development of simple, often inexpensive, Pd-catalysts and C-C bond forming conditions.
APPENDIX A
12 Principles of Green Chemistry Developed by Paul Anastas and John Warner
1. Prevention - It is better to prevent waste than to treat or clean up waste after it has been created.
2. Atom Economy - Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product. 3. Less Hazardous Chemical Syntheses – Wherever practicable, synthetic
methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.
4. Designing Safer Chemicals – Chemical products should be designed to affect their desired function while minimizing their toxicity.
5. Safer Solvents and Auxiliaries – The use of auxiliary substances (e.g., solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used.
6. Design for Energy Efficiency – Energy requirements of chemical processes should be recognized for their environmental and economic impacts and should be minimized. If possible, synthetic methods should be conducted at ambient temperature and pressure.
7. Use of Renewable Feedstocks – A raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable.
8. Reduce Derivatives – Unnecessary derivatization (use of blocking groups, protection/ deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste.
9. Catalysis – Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.
10. Design for Degradation – Chemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment.
11. Real-time analysis for Pollution Prevention – Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances.
12. Inherently Safer Chemistry for Accident Prevention – Substances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, explosions, and fires.