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People, Travel, Seminars, Reading, the Classroom, and Curiosity–Sources of Research Inspiration

 

R. Daniel Little

 

Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA 93106–9510, little@chem.ucsb.edu.

 

Received January 5, 2010
Accepted March 16, 2010

 

Abstract

This manuscript is the outgrowth of a plenary lecture delivered by the author at the 44^th Congreso Mexicano de Química that was held in Puebla, Mexico from 26–30 September of 2009. In formulating the presentation, consideration was given to thinking about the origins of the ideas that were integral to the formulation of the research to be described. The intent was to address the younger members of the audience – advanced undergraduate and graduate students, and those beginning the process of searching for a job. At a similar stage in my scientific career, I realized the need to formulate research plans in order to complete job applications where they were required. Where do these ideas come from? What factors stimulate one's curiosity? What stimulates one to pursue a particular line of research? Topics discussed within the context of attempting to address these questions include electrohydrocyclization and electroreductive cyclization, and their application to the total synthesis of natural products, the use of nickel salen and triarylamines as mediators and redox catalysts, the regiospecific rearrangement of cation radicals derived from strained hydrocarbons and the application of the chemistry to the synthesis of a sesquiterpene, and finally, a discussion of the role redox chemistry may play in the expression of the bioactivity of the pseudopterosin class of marine natural products.

Keyword: Electrohydrocyclization, redox, chemical synthesis, rearrangements, pseudopterosin.

 

Resumen

Este escrito es el resultado de una conferencia plenaria impartida por el autor en el 44o Congreso Mexicano de Química, realizado en Puebla, México, del 26 al 30 de Septiembre del 2009. Al preparar la presentación, se tomó en consideración el origen de las ideas que motivaron la investigación que se describió. Este intento fue dirigido a los miembros mas jóvenes de la audiencia, a los alumnos de licenciatura y posgrado, y a aquellos en búsqueda de trabajo. En una etapa similar de mi carrera científica, me dí cuenta de la necesidad de formular planes de investigación requeridos para completar las solicitudes de trabajo. ¿De dónde vinieron esas ideas? ¿Cuales son los factores que estimulan la curiosidad? ¿Cual es la motivación para seguir una línea particular de investigación? Los temas que se discuten en el contexto de intentar abordar estas preguntas incluyen la electrohidrociclización y la ciclización electroreductiva, y sus aplicaciones en la síntesis total de productos naturales, el uso del níquel salen y trietilaminas como mediadores y catalizadores redox. las transposiciones regioespecíficas de cationes radicales derivados de hidrocarburos tensionados y la aplicación de la química a la síntesis de un sesquiterpeno, y finalmente, se incluye una discusión del papel que la química redox puede jugar en la expresión de la bioactividad de los productos naturales marinos del tipo pseudopterosina.

Palabras clave: Electrohidrociclización, redox, síntesis química, transposiciones, pseudopterosinas.

 

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References

1. The science described in this manuscript is the outgrowth of a plenary lecture delivered by the author at the 44th Congreso Mexicano de Química organized by the Sociedad Química de México that was held in Puebla, Mexico from 26–30 September of 2009.         [ Links ]

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5. Interest in the area was first piqued while attending graduate school at the University of Wisconsin. Electrochemistry seemed to have many aspects in common with photochemistry, the study of which was the author's major area of focus at the time.         [ Links ]

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8. The author expresses his appreciation to Professor Joseph W. Horton for being such an excellent and inspirational teacher.         [ Links ]

9. Little, R. D.; Fox, D. P.; Van Hijfte, L.; Dannecker, R.; Sowell, G.; Wolin, R. L.; Moens, L.; Baizer, M. M. J. Org. Chem. 1988, 53, 2287–94.         [ Links ]

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16. The Dieckmann cyclization provides a good example. Thus, the initial acid–base reaction between a metal alkoxide and an ester clearly resides on the side of the starting materials. Nevertheless, the small amount of enolate that does form undergoes cyclization leading to the formation of a β–keto ester. The success of the process relies upon the fact that the proton residing between the carbonyl carbons in the product is the most acidic of all species present in the reaction mixture. Its removal irreversibly shifts the overall equilibrium to the product.         [ Links ]

17. (a) Olivero, S.; Rolland, J.–P.; Dunach, E.; Labbe, E. Organometallics 2000, 19, 2798–2804.         [ Links ] (b) The original inspiration stemmed from listening to Professor Dunach when she discussed the use of nickel salen and nickel cyclam to achieve selective transformations involving allyl aryl ethers. Her presentation was delivered to the 53rd Meeting of the International Society of Electrochemistry that was held in September of 2002 in Düsseldorf, Germany.         [ Links ]

18. Miranda, J. A.; Wade, C. J.; Little, R. D. J. Org. Chem. 2005, 70, 8017–8026.         [ Links ]

19. (a) Goken, D. M.; Ischay, M. A.; Peters, D. G.; Tomaszewski, J. W.; Karty, J. A.; Reilly, J. P.; Mubarak, M. S. J. Electrochem. Soc. 2006, 153, E71–E77.         [ Links ] (b) Raess, P. W.; Mubarak, M. S.; Ischay, M. A.; Foley, M. P.; Jennermann, T. B.; Raghavachari, K.; Peters, D. G. J. Electroanal. Chem. 2007, 603, 124–134.         [ Links ]

20. Calculations were carried out using Windows, Macintosh and Linux software supplied by Wavefunction, Inc. of Irvine, CA.         [ Links ]

21. "Electron Transfer in Inorganic and Organic Chemistry", a symposium held at the Westfalische Wilhelms–Universitat in Münster, Germany in November of 2000.         [ Links ]

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25. Park, Y. S.; Little, R. D. J. Org. Chem. 2008, 73(17), 6807–6815.         [ Links ]

26. Park, Y. S.; Little, R. D. Electrochimica Acta, 2009, 54, 5077–5082.         [ Links ]

27. (a) Look, S. A.; Fenical, W.; Matsumoto, G. K.; Clardy, J. J. Org. Chem. 1986, 51, 5140–5145;         [ Links ] (b) Roussis, V.; Wu, Z.; Fenical, W.; Strobel, S. A.; Van Duyne, G. D.; Clardy, J. J. Org. Chem. 1990, 55, 4916–4922;         [ Links ]

28. Zhong, W.: Moya, C.; Jacobs, R. S.; Little, R. D. J. Org. Chem. 2008, 73, 7011–16.         [ Links ]

29. The photo is from the web site: http://www.iquimica.unam.mx/biblioteca.html.         [ Links ]

30. The phrase "child in a candy store" refers to the delight most children feel when they enter a candy store.         [ Links ]

31. Corey, E. J.; Czakó, B.; Kürti, L. Molecules and Medicine; Wiley Interscience: New York, NY, 2007.         [ Links ]

32. (a) Tanis, V. M.; Moya, C.; Jacobs, R. S.; Little, R. D. Tetrahedron, 2008, 64, 10649–10663.         [ Links ] (b) Zhong, W.; Moya, C.; Jacobs, R. S.; Little, R. D. J. Org. Chem. 2008, 73, 7011–7016.         [ Links ]

33. Hoarau, C.; Day, D.; Moya, C.; Wu, Guang; Hackim, A.; Jacobs, R. S.; Little, R. D. Tetrahedron Lett. 2008, 49, 4604–4606.         [ Links ]

34. Zhong, W.; Little, R. D. Tetrahedron, 2009, 65, 10784–10790.         [ Links ]

35. Unpublished results of Dr. Wei Zhong and Mr. Daniel Day, UCSB.