Illinois Wesleyan University Digital Commons @ IWU Honors Projects Chemistry 2009 Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate Catalyzed Allylation of Cyclic Acetals Matthew J. Spafford, '09 Illinois Wesleyan University Follow this and additional works at: https://digitalcommons.iwu.edu/chem_honproj Part of the Physical Sciences and Mathematics Commons Recommended Citation Spafford, '09, Matthew .,J "Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate Catalyzed Allylation of Cyclic Acetals" (2009). Honors Projects. 33. https://digitalcommons.iwu.edu/chem_honproj/33 This Article is protected by copyright and/or related rights. It has been brought to you by Digital Commons @ IWU with permission from the rights-holder(s). You are free to use this material in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This material has been accepted for inclusion by faculty at Illinois Wesleyan University. For more information, please contact [email protected]. ©Copyright is owned by the author of this document. Green Chemistry Using Bismuth Compounds: Bismuth(III) TriflateCatalyzed Allylation of Cyclic Acetals Matthew J. Spafford Advisor: Dr. Ram Mohan Research Honors Senior Thesis Illinois Wesleyan University Spring 2009 Approval Page i Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate Catalyzed Allylation of Cyclic Acetals By Matthew Spafford 1. A PAPER SUBMITTED AS PART OF THE REQUIREMENTFOR RESEARCH HONORS IN CHEMISTRY Approved: Ram S. Mohan, Ph. D., Research Advisor ! Brian B. Brennan, Ph. D. "�Rebeccaa� Roesner, Ph. D. Nathan Frank,Ph. D. Illinois Wesleyan University, April 20, 2009 Acknowledgements I would first like to thank my research advisor and friend,Dr. Ram Mohan, for all his support and encouragement over the past years. He has instilled a passion for chemistry in me throughhis teaching and for that, I very much indebted to him. His guidance and support has am been instrumental in shaping me as a scientist. I also very gratefulfo r the countless hours he am has spent on my behalf, without which this dissertation would not have been possible. I would also like to thank Dr. Brian Brennan, Dr. Rebecca Roesner, and Dr. Nathan Frank for serving on my thesis committee. A special thanks is in order for the all members of the research group over the past years: Aaron Bailey and Erin Anderson for their especial patiertce while training me as a Sophomore; Scott Krabbe for his synthesis of dioxanes and his wonderfulcountry music collection; Dr. Eeshwar Begari for his early work on the allylation of dioxanes; Jay Christensen, Matthew Huddle, and Josh Lacey for their work on the allylation of dioxolanes; Pash DeVore, JP Carolan, Kendall Tasche, Jason Bothwell, Dan Podgorski, Maggie Olsen, Long Le, Jamie Rogers, Herbie Yung, Justin Emat, Ashvin Bam, Ann Palma, Veronica Angeles, Paul Sierszulski, and Phil Lazzara for makingtime in lab over the past years such a great time. I also need to acknowledge Cindy Honegger for all of her help in the stockroom over the past two years. None of this work would have been possible if not for her assistance. 11 The Twelve Principles of Green Chemistry 1. Prevention: It is better to prevent waste than to treat or clean up waste afterit 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 effect 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. Design for Energy Efficiency: Energy requirements of chemical processes 6. should be recognized fo r 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, temporarymodifica tion 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 oftheir 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 furtherdeveloped to allow for real-time, in-process monitoring and control 111 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. Anastas, P. T.; Warner, J. C. Green Chemistry, Theory and Practice. Oxford University Press, New York, 1998, 30. IV Abstract Bi(OTfh (2.0 mol %) (1.7 �SiMe3 eq) x�) n R1.-lX X=O, S n = 1,2 Cyclic acetals (dioxolanes, dioxanes, and dithianes) are common protecting groupsin organic synthesis but they can also be converted to other usefulfunctional group s. A bismuth(III)triflate-catalyzed multi component reaction involving the allylation of cyclic acetals followed by in situ derivatization with acid anhydrides to generate highlyfunctionalized esters and thioesters has been developed under solvent-free conditions. Most reagents used to date for the allylation of cyclic acetals are highly corrosive or toxic and are oftenrequired in stoichiometric amounts. In contrast, the use of a relatively non-toxic and non-corrosive bismuth(III) based catalyst makes this methodology benign and attractive. v Table of Contents I. Introduction.. .................. .... ................. ....................... ....... ..... ..... ..... .......... .... .......... ... 1 A. Green Chemistry ........................................................................... 1 B. Bismuth Compounds ......................................................................... 7 C. Literature Review: Allylation of Acetals .............................................. 21 II. Results and Discussion ....................................................................... 32 A. Bismuth(III) TriflateCatalyzed Allylation of 1,3-Dioxolanes ..................... 32 B. Mechanistic Studies .......................................... ........................... 37 C. Bismuth(III) TriflateCatalyzed Allylation of 1,3-Dioxanes. ................ ....... 39 D. Bismuth(III) Triflate Catalyzed Allylation of 1,3-Dithianes.................... ... 41 III. Experimental. .. .. .. 45 A. General Experimental. ................................................. ........... ..... 45 B. Bismuth(III) TriflateCatalyzed Allylation of 1,3-Dioxolanes ..... ............. 46 C. Bismuth(III) TriflateCatalyzed Allylation of5,5-Dimethyl-1,3-Dioxanes ..... 53 D. Bismuth(III) TriflateCatalyzed Allylation of 1,3-Dithianes ...................... 56 IV. References ...................................................................................... 63 V. Appendix: Spectral Data ..................................................................... 70 VI. VB I. Introduction A. Green Chemistry The contributions ofthe phannaceuticalindustry, especially via synthetic organic chemistry, to medicine have significantly improved the quality and length of human life. The synthesis and commercial development of countless compounds now allow for the treatment of diseases that have otherwise overwhelmed mankind. Over the past century, the discovery of antibiotics and new medicines has contributed to prolonging the average human life span by nearly thirty years.! The development of new fertilizers and pesticides has allowed for more bountifulharvests. Despite the vast achievements of the chemical industry, the massive amounts of hazardous waste produced cannot be ignored, especially when considering current environmental issues and the hazards presented to human health. For example, in 1984 a Union Carbide pesticide plant in Bhopal, India released 42 tons of methyl isocyanate? Nearly 15,000 people have lost their lives as result of this toxic gas leak and many others have suffered health problems due to exposure. Environmental drinking water contamination has also been a major issue in the aftermathof the disaster. The United States Congress has passed many laws to help reduce the amount of chemical waste released into the environment. The most significant of these is the "Pollution Prevention Act" (PP A) passed in 1990.3 The PPA provides guidelines and laws on pollution prevention through the proper use and disposal of chemicals. Also, source reduction and prevention have been stressed in this legislation. The governmenttracks the