The focus of this project is to advance understanding of the mechanisms and selectivities of recently introduced reactions, on the investigation of new reactions, and on the use of new reactions to produce novel scaffolds, materials, ligands, and catalysts. The research will include studies on the regioselectivity of [5+2] cycloadditions, studies of new 5- and 3-carbon agents for new [5+2] and [3+2] cycloadditions, serial [5+2]/[4+2] cycloadditions and a new [5+2]/Nazarov process for one step syntheses of [5.3.0] systems, studies on [3+2] cycloadditions of vinylaziridines (VA), Lewis acid mediated [3+2] cycloadditions of VAs, metal catalyzed [2+2+2+2] cycloadditions to produce cyclooctatetraenes and the use of these to make new materials, ligands, and catalysts.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Paul Wender in the Department of Chemistry at Stanford University. Professor Wender's research seeks to create new ways of doing synthesis and to use that expertise to advance the frontiers of chemistry, biology, medicine and materials science. New reactions offer new ways to think about synthetic problems, new process options that could minimize or avoid environmentally problematic steps and process inefficiencies, and often new mechanisms and insights that add to our basic knowledge of bonding, structure, and reactivity. At its most fundamental level, synthesis provides the opportunity to create new compounds with functions that advance knowledge of chemistry and open opportunities for the preparation of materials of value to our society including probes, medicines, materials, fine chemicals, agricultural chemicals, and functional devices.
Final Report for Period through April 30, 2012 Principal Investigator: Wender, Paul A. Award ID: 0848280 Organization: Stanford University Submitted By: Wender, Paul - Principal Investigator Title: Approaches to Improved Synthesis Design: Mechanistic and Synthetic Studies on New Annelation Methods This project has evolved over a 30-year period and has been directed at two overarching and inter-connected goals: training scientists who will drive scientific advances of economic and societal benefit and creating transformative advances in reaction science with an emphasis on the development of new reactions and the elucidation of mechanisms pertinent to their predictive use. With respect to the former, over 300 coworkers have been trained in the PI’s lab and over 70 are now holding research and teaching positions in academia while most other former trainees are leading advances in biotech, pharma, ag chem., and fine chemical industries with many in positions of leadership including directors, vice-presidents and the current CEO of a major company. With respect to new reaction science, we have designed or discovered over 25 new or novel reactions and attendant mechanisms. New reactions are to the making of molecules (synthesis) what new words are to our language. Expanding the lexicon of reactions is critical to being able to achieve goals that go beyond past practices. We seek to improve reactions by making them more efficient, selective and green. Of even greater importance is creating new reactions as they change how we think about bond construction and provide options for achieving greener solutions to the construction on drugs, diagnostics, imaging agents and materials. The PI has been a leading proponent of step economy, the ideal synthesis and function oriented synthesis which collectively form the basis of green technologies of the future. Our work also has collateral benefit on science conducted in other groups as it serves to inspire similar cutting edge studies in other groups supported by the NSF. A reaction that we introduced in 1995, for example, has now evolved into impressive studies on related reactions and new catalysts in many other groups around the globe. Over 12 groups have impressively contributed to the development of this one process. Many other reactions have received similar attention. Our own studies have further spawned new ways to make molecules of scientific and societal value including taxol, a agent for the treatment of breast and ovarian cancer; prostratin, a lead for a potential first-in-class therapy, namely the eradication of HIV/AIDS; and bryostatin, a lead compound for the first-in-class treatment of Alzheimer’s disease. The NSF supported our program in synthesis and that core served these various first-in-class approaches to transformative therapies. It has also supported new catalyst development and has led to new insights of mechanistic importance. Our core expertise has also enabled advancement of science in many other groups that work in collaboration with our group. These collaborative studies involve new imaging strategies for early disease detection, new strategies for drug delivery, and new tools for energy and basic research. This program has thus enabled or enhanced progress in many other groups with whom the PI collaborates. These include up to 25 collaborations in academia and industry. These national and international collaborations forge connections that serve to strengthen the global scientific community and thereby our ability work together is creating better science, materials, imaging agents, and therapies. The core skills and expertise developed in this project also have provided the basis for new and more effective approaches to scientific education. The PI has lectured extensively in courses at Stanford but also nationally and internationally. The experiences and science developed in this project have figured in providing a more effective education to those in attendance. The PI has taught over 10,000 undergraduates and several hundred graduate students during the 30-year project. In addition, many students supported by this project have also been involved in teaching. In addition, many have conducted outreach in local schools. In addition, these NSF studies have enabled solutions to problems in industry through consultation. The expertise developed has enabled the creation and advancement of companies, providing solutions to problems of significance as well as job opportunities. The PI has also been called on to lead or participate in policy and grant decisions, including many related to NSF function. The PI has also actively supported others in their efforts to secure funding and to advance science. The PI has also taken an active role in science education for the public, having been a participant in numerous articles, TV programs and other methods of science dissemination. The PI has also participated with others in building an awareness of the critical importance of scientific education and research and in making the public aware of how little support is required to produce so much societal and economic gain.
