1. 1 “Greening Up” Organic Reactivity in the Undergraduate Laboratory Dr. Andy Dicks Department of Chemistry University of Toronto Green Chemistry and Engineering Conference 25 th June 2008

2. 2 Today’s Presentation l CHM 343H - “Organic Synthesis Techniques” - background to a new course l CHM 343H Experiment Types l Aqueous Horner-Wadsworth-Emmons, Suzuki and Heck reactions l Conclusions

3. 3 CHM 343H - “Organic Synthesis Techniques” (1) l Chemistry specialists/majors only l Enrolment = 37 in Spring 2008, 48 laboratory hours, 26 lab-related lectures l C-C bond-forming reactions l Catalytic methodologies (transition metal, phase-transfer, organo, bio, Lewis/Brønsted acid)

4. 4 CHM 343H - “Organic Synthesis Techniques” (2) l Eight “green chemistry” lectures: (a) Impact on Synthetic Organic Chemists: - Yields and Experimental Atom Economies (~ 2) - Alternative Synthetic Pathways/Conditions (~ 2) - Choice of Solvents and Reagents (~ 1) (b) Industrial Examples (Ibuprofen, Viagra etc.) (~ 3)

5. 5 “Hooks” For New CHM 343H Experiments l “Discovery-based” experiments involving problem-solving and student input l “Real-world relevant” organic synthesis l “Green chemistry”: (a) microscale reactivity (b) performing reactions “solvent-free” (c) catalytic strategies (d) replacing organic solvents with water

6. 6 “Traditional” Sunscreen Analog Synthesis Mohrig, J. R. et al. In Modern Projects And Experiments In Organic Chemistry: Miniscale And Standard Taper Microscale, 2 nd Ed., 2003, p. 197-202 Active ingredient: octyl 4-methoxycinnamate

7. 7 “Greening Up” Sunscreen Analog Synthesis Horner-Wadsworth-Emmons reaction in water, single step Chem. Educator [Online], 2005, 10, 300-302

8. 8 Previous JCE Suzuki Reaction Ketone product reduced to alcohol and isolated Use of triphenylphosphine and n-propanol Callam, C.S.; Lowary, T. L. J. Chem. Educ., 2001, 78, 947-948

9. 9 Aqueous Suzuki NSAID Analog Synthesis Active ingredient: diflunisal (Merck) Suzuki reaction in water Elimination of organic solvents/bases to form an anti-inflammatory analog J. Chem. Educ., 2008, 85, 555-557

10. 10 Previous JCE Heck Reaction Cinnamic acid product Use of acetonitrile and triethylamine Martin, W. B.; Kateley, L. J. J. Chem. Educ., 2000, 77, 757-759

11. 11 “Greening Up” The Heck Reaction Elimination of organic solvents/bases Heck reaction in water Chem. Educator [Online], 2007, 12, 77-79

12. 12 Aqueous Reactivity: Conclusions l Organometallic reactions (particularly Pd-catalyzed ones) facile in water l More classical enolate chemistry possible l Yields comparable to or better than in organic solvents l Often improvement in reaction times l Opportunity to discuss “green chemistry” principles in lecture and lab

13. 13 Acknowledgements CHM 449Y: Summer Research: Jason McIntee (2002) June Lin (2004) Vangelis Aktoudianakis (2003) Lawrence Cheung (2004) CHM 299Y 2005/06: $$$: Elton Chan Xerox (J. Lin) Amanda Edward Isabel Jarosz Department of Chemistry Vicki Lee Scholar Fund (CHM 299Y) Leo Mui Sonya Thatipamala A&S Instructional Initiative Grant (CHM 449Y)

14. 14 Publications Chem. Educator [Online], 2005, 10, 300-302 (Horner-Wadsworth-Emmons) Chem. Educator [Online], 2007, 12, 77-79 (Heck) J. Chem. Educ., 2008, 85, 555-557 (Suzuki) adicks@chem.utoronto.ca