LEARNING OUTCOMES OF THE ADVANCED MODULE that are worked on in this course:



1. CM07. Know how to apply the knowledge of structural analysis and organic reactivity to the synthesis of drugs and molecules of biological interest.

2. CM08. Design and plan experiments efficiently to solve real chemical problems.

3. CM09. Interpret and discuss the relevant results derived from the experimental activity and translate the conclusions in the form of scientific-technical reports and oral presentations.

4. CM11. Be able to explain both orally and in a written form, in a comprehensive manner, phenomena and processes related to Chemistry and related subjects, in Basque and / or Spanish and English.

5. CM18. Know the strategies that allow the design of synthetic processes for organic molecules, including the adequate methodology for the preparation of enantio-enriched substances.

6. G002. Manage appropriately the acquired knowledge and skills to recognize and analyze new problems and propose strategies to solve them.

1. THE DESIGN OF ORGANIC SYNTHESES. RETROSYNTHETIC ANALYSIS. Introduction to Target-oriented Synthesis. The basics of retrosynthetic analysis: Disconnection, synthon, synthetic equivalent, transforms, retron. Retrosynthetic strategies. Identification of strategic bonds.



2. FUNCTIONAL GROUPS INTERCONVERSION. PROTECTIVE GROUPS. Addition of functional groups (activation). Oxidation level adjustments. Protective groups.



3. DISCONNECTIONS IN MONO- AND DIFUNCTIONALIZED COMPOUNDS. Types of synthons. Natural polarity. Single functional group C-X and C-C disconnections. Two-functional-group C-X and C-C disconnections (1.1, 1.3 and 1.5 relationships). Two-functional-group C-C disconnections (1,2, 1,4 and 1,6 relationships). Transition metal mediated cross coupling reactions. Polarity inversion. Reconnections Rearrangements and fragmentations. Carbon-carbon double bond disconnections.



4. SYNTHESIS OF CYCLIC COMPOUNDS. Cyclization reactions. Thorpe-Ingold effect. Baldwin rules. Three-membered ring formation; carbene intermediates. Four-, five- and six-membered ring formation; pericyclic and radical reactions. Ring expansion and ring contraction reactions. Formation of of cycles of 7 or greater members.



5. STEREOCONTROLLED REACTIONS. Generation and loss of stereogenic centers. Stereoselective and stereospecific reactions. Conformational and steric effects in chemical reactivity. Felkin-Ahn and Zimmerman-Traxler models. Asymmetric synthesis. Catalytic enantioselective reactions: Epoxidation, dihydroxylation, metal hydride carbonyl reduction and catalytic hydrogenation. Organocatalysis.

Lectures. The teacher will develop the subject explaining all those aspects required to facilitate the understanding and assimilation of the didactic material available to students (textbooks and on-line supplementary material, including exercises/problems).



Classroom exercises/discussions. Their purpose is to illustrate and to exercise the basic principles of the course. The starting point will be a series of exercises proposed by the teacher, where real problems are raised in the context of the preparation of complex molecules. The possible solutions will be discussed to determine the most appropriate one. The direct and personal participation of the students will serve to evaluate their progress, and this will be complemented with individually graded written tests. These tests will include the individual resolution of exercises and/or problems related to any aspect of the topics covered in the course.



Seminars. They will be used for the discussion of synthetic problems selected from the literature due to their special interest, difficulty or novelty. This will include the student presentation and discussion of the synthetic approach, as well as of the actual synthesis of the target molecules. The students performance will be taken as a partial measure of the degree of assimilation achieved throughout the course.

CONTINUOUS EVALUATION:



- Resolution of exercises and problems. Weight in the final grade: 40%. A minimum of four points out of ten is required.



- Discussion and presentation of literature examples. Items to be graded will include the participation in the discussion and the quality of the personal work carried out (previous preparation, success in the resolution of the synthetic problem, degree of understanding and answers to the questions). Weight in the final grade: 10%. A minimum of four points out of ten is required.



- Written exam. Resolution of exercises and/or problems related to any aspect of the topics covered in the course. Weight in the final grade: 50%. A minimum of five points out of ten is required.



- Opting out of Continuous Evaluation. Students who wish to be evaluated through the final evaluation system must decline the option of continuous evaluation by writing presented to the teaching staff responsible for the course within a period of 12 weeks from the beginning of the semester in which the course is taught.



END-OF-COURSE EVALUATION:



- Written exam. Resolution of exercises and/or problems related to any aspect of the topics covered in the course. Weight in the final grade: 100%. A minimum of five points out of ten is required.



- Opting out. Failure to attend the exam will result in no evaluation (No Show).

Basic bibliography

Basic textbooks (lecture and exercises):



- Carruthers, W.; Coldham, I. Modern Methods of Organic Synthesis, 4th ed., Cambridge University Press, 2004.



- Starkey, L. S. Introduction to Strategies for Organic Synthesis. Wiley: Hoboken N.J., 2012; 2nd ed. 2018.



Additional textbooks for exercises:



- Carda, M.; Marco, J. A.; Murga, J.; Falomir, E. Análisis Retrosintético y Síntesis Orgánica. Resolución de ejemplos prácticos. Editorial Universitat Jaume I: Castellón, 2010.

In-depth bibliography

- Warren, S.; Wyatt, P. Organic Synthesis: The Disconnection Approach; 2nd ed. Wiley: 2011.

- Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic Chemistry; Oxford University Press: New York, 2001; 2nd ed. 2012.

- Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Solution manual to accompany Organic Chemistry; Oxford University Press: New York, 2001.

- Wade, L. G. Organic Chemistry; Pearson Prentice Hall: New Jersey, 2010.

- Vollhardt, K. P. C.; Schore, N. E. Química Orgánica: Estructura y Función, 3rd ed.; Omega: Barcelona, 2007.

- McMurry, J. Organic Chemistry 7th Ed.; Brooks/Cole: Belmond, 2008.

- Quiñoá, E.; Riguera, R. Cuestiones y Ejercicios de Química Orgánica; Ed. McGraw Hill: Interamericana de España: Madrid, 1994.

- Vollhardt, K. P. C.; Schore N. E. Study Guide and Solutions Manual for Organic Chemistry, 3rd Ed.; W. H. Freeman and Co.: New York, 1999.

Journals

Advanced Synthesis and Catalysis: http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1615-4169
Angewandte Chemie International Edition: http://www3.interscience.wiley.com/journal/117943443/tocgroup
Chemical Communications: http://www.rsc.org/publishing/journals/CC/Article.asp?Type=CurrentIssue
Chemistry - A European Journal: http://onlinelibrary.wiley.com/doi/10.1002/chem.v18.30/issuetoc
Chemistry – An Asian Journal: http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1861-471X/issues
European Journal of Organic Chemistry: http://www3.interscience.wiley.com/journal/27380/home
Journal of Chemical Education:http://jchemed.chem.wisc.edu/
Journal of the American Chemical Society: http://pubs.acs.org/journal/jacsat
The Journal of Organic Chemistry: http://pubs.acs.org/journal/joceah
Organic and Biomolecular Chemistry: http://www.rsc.org/Publishing/Journals/Ob/Index.asp
Organic Letters: http://pubs.acs.org/journal/orlef7
Organic Syntheses: http://www.orgsyn.org/
Synthesis: http://www.thieme-connect.de/ejournals/journal/10.1055/s-00000084
Synlett: http://www.thieme-connect.com/products/ejournals/issue/eFirst/10.1055/s-00000083
Tetrahedron: http://www.sciencedirect.com/science/journal/00404020
Tetrahedron Letters: http://www.sciencedirect.com/science/journal/00404039%20