UIB
Universitat de les
Illes Balears
Masters in Chemical Technology and Science
SUBJECT DESCRIPTION
Details
Subject
Name of subject: Asymmetric Synthesis and Catalysis
Code: 10136
Type: Optional
Level: Postgraduate
Year: 1
Semester: 1
Timetable:
See general course programme
Timetabled within module MCTQ2: Organic Chemistry
Language: Spanish
Teaching staff
Subject leader
Name: Dr. José M. Saá Rodriguez
Contact: jmsaa@uib.es
Pre-requisites:
It is preferable to have passed ‘Organometallic Compounds in Synthesis’.
Number of ECTS credits: 5
Contact hours: 50
Independent study hours: 85
Key terms:
Asymmetric synthesis. Asymmetric Catalysis.
General subject aims
The theoretical knowledge that students will gain in this course will prepare them for
research in public and private institutions in the areas of asymmetric synthesis and
catalysis.
Subject skills and objectives
Specific:
 A good command of stereochemistry.
 A good command of preparing and determining the purity of enantiomerically
pure compounds (EPCs).
 A good command of asymmetric synthesis methodology.
 A good command of asymmetric catalysis methodology.
General:
 Be able to apply knowledge to practice.
 Be able to analyse information and synthesise concepts.
 Be able to communicate with others and work as part of team.
 Be able to work individually and plan and manage time.
Content
1. Introduction. Basics of stereochemistry (DP, 2 hours)
2. Routes to enantiomerically pure compounds (DP, 2 hours)
Case study (TEI, 1 hour): “Familiar” solution to racemates (T. Vries, H. Wynberg, Q.B.
Broxterman, S.v.d. Sluis et al. Angew.. Chem.. Int.. Ed.. Engl. 1998, 37, 2349; ibid
1998, 37, 3239; Synthesis 2003, 10, 1626)
3. Asymmetric synthesis: basic principles. Stereoselective synthesis: chiral auxiliaries
(DP, 2 hours).
Case study (TEI, 1 hour): aldol condensations with chiral Evans enolates (N-acyl
oxazolidinones and similar: see D. Evans et al. J. Am. Chem. Soc. 1981, 103, 2876; ibid
1981, 103, 3099; J. Org. Chem. 1986, 51, 2391; ibid. 1997, 119, 7883; ibid. 1991, 113,
1047; Thornton et al. J. Am. Chem. Soc. 1989, 111, 5722; ibid. 1991, 113, 1299; J. Org.
Chem. 1991, 56, 2489; M. Crimmins et al. J. Am. Chem. Soc. 1997, 119, 7883).
4. Simple, dynamic and parallel kinetic resolutions (DP, 2 hours)
Case study (TEI, 1 hour): catalysts for the kinetic resolution of alcohols through Oacylation (see E.N. Jacobsen et al. Adv. Synth. Catal. 2001, 343, 5 and indicated
references).
5. Basic principles of asymmetric catalysis: multiplication of chirality. Non-linear
effects: amplification of chirality. Monofunctional and multifunctional catalysis. The
role of additives (DP, 2 hours).
Case study (TEI, 1 hours): addition of organozincs to carbonilic compounds (R. Noyori,
et al Angew. Chem. Int. Ed. Engl. 1991, 30, 49 and indicated references).
6. Enantioselective organocatalysis (DP, 3 hours).
Case study (TEI): reactions to aldol condensation and similar catalysed by proline (see
P. I. Dalko et al. Angew. Chem. Int. Ed. Engl. 2001, 40, 3726 and indicated references).
7. Asymmetric catalyses through concerted and coupling reactions (DP, 3 hours; SyC, 2
hours).
Case study (TEI): enantioselective catalysts in homo and hetero Diels-Alder reactions
(E. J. Corey, Angew. Chem. Int. Ed. Engl. 2002, 41, 1650; K.A. Jorgensen et al. Angew.
Chem. Int. Ed. 2000, 39, 3558).
8. Asymmetric catalysis through chiral metallic complexes I: addition of H-M and H-C
bonds to multiple C=C and C=X bonds (DP, 4 hours).
Case study (TEI): Catalytic hydrogenation of double bonds (J. M. Brown, Chem. Soc.
Rev. 1993, 25 and indicated references).
9. Asymmetric catalysis through chiral metallic complexes II: addition of C-M bonds to
multiple C=C, C=X and C=C-C=X bonds (DP, 4 hours).
Case study (TEI): nitroaldol condensation and similar caused by heterobimetallic
catalysts (M. Shibasaki et al., Angew. Chem. Int. Ed. Engl. 1997, 36, 1237; Adv. Synth.
Catal. 2002, 344, 3; Chem. Rev. 2002, 102, 2187).
10. Asymmetric catalysis through chiral metallic complexes III: oxidation (epoxidation,
dihydroxylation and aminohydroxylation) of C=C bonds and heteroatoms (DP, 4 hours).
Case study (TEI): dihydroxylation of double bonds (see T. Katsuki in Comprehensive
Asymmetric Catalysis vol. 2, 621; K.B. Sharpless et al. Chem. Rev. 1994, 94, 2483; P.
Obrien, Angew. Chem. Int. Ed. Engl. 1999, 38, 326).
11. Asymmetric catalysis through chiral metallic complexes IV: isomerisation and
cycloaddition n+m+p reactions (DP, 1 hour; SyC ,2 hours).
Case study (TEI): (-)menthol synthesis (R. Noyori in Asymmetric Catalysis in Organic
Synthesis, 1994, chap. 3, p. 95).
12. Asymmetric catalysis in non-conventional media (“green” asymmetric catalysis;
DP).
Case study (TEI): recoverable and reusable catalysts (J. A. Gladysz, Pure Appl. Chem.
2001, 73, 1319).
Methodology and student work plan
1. Learning methods: Attendance at theory classes.
Class work
Group size: Intermediate
2. Learning methods: Individual tutorials
Physical and /or via e-mail
Use of e-learning: Information on the web, e-mail
Group size: Individual
3. Learning methods: Coursework and seminars
Independent study
Use of e-learning: Information on the web, e-mail
Group size: Individual and/or small groups
4. Learning methods: Preparing for exam
Independent study
Use of e-learning: Information on the web, e-mail
Group size: Individual
5. Learning methods: Tests and exams
Independent study
Use of e-learning: Information on the web, e-mail
Group size: Individual
This subject’s main aim is to provide students, under the supervision of tutors, with
knowledge and skills in a constantly developing area of knowledge, namely asymmetric
catalysis and synthesis. To do so, we believe that the syllabus cannot be exclusively
based on a classical attendance-based learning experience, but rather participative
learning which aims for an personalised learning experience. As such, it comprises
attendance based classes (DP), as well as seminars and conferences (SyC) and
individual presentations (TEI) by the students themselves as fundamental elements of
learning. Furthermore, independent study (EI) and individual tutorials (TI) are vital.
Regarding classes (DP), the course aims to provide students with a wide (although not
exhaustive) view of a vast area of knowledge that is still expanding strongly, especially
in terms of catalysis. This is why more emphasis is placed on catalysis than
diastereoselective synthesis.
Since, according to Noyori, ‘asymmetric catalysis is the fourth dimension of chemistry’,
the course’s aim is approached using an approximative methodology that firstly revises
knowledge of stereochemistry (x, y and z dimensions) by means of the first three
sections, and then poses the difficulties in controlling the fourth dimension (t), i.e.
kinesis. Classes in the first block (sections 1-5, 10 hours) and the second block (sections
6-12, 20 hours) require attendance, and students will need to dedicate at least 35 hours
of study to assimilate information from these and a further 35 for seminars, attending
occasional conferences and case studies, which in turns requires student participation in
presentations (TEI). To study class material and prepare seminars and coursework,
students will have to resolve any doubts and be clear about concepts, which implies 15
hours dedicated to individual tutorials with staff. In fact, for each section a case study
has been proposed (which will be changed every two years) which students will present
and students and teachers will debate together. For the preparation and holding of
exams and tests there are a further 15 + 5 hours.
The course bears 5 credits, distributed thus: 30 hours of classes; 35 hours of
independent study; 35 hours of presentations, seminars and conferences; 15 hours of
tutorials and 20 hours for exams and tests. Students must attend 80% of classes to be
able to pass the course.
Learning agreement and assessment criteria and instruments
Assessment criteria:
Exams (40%)
Seminars (30%)
Coursework (20%)
Tutorials (10%)
Is assessment organised by means of a learning agreement? No
Bibliography, resources and appendices
Monographs:
Dale L. Boger "Modern Organic Synthesis" TSRI Press , 1999, San Diego, Ca., USA
E.L. Eliel, S.H. Wilden “Stereochemistry of Organic Compounds”, Wiley Interscience
1994.
J.D. Morrison, ed. "Asymmetric Synthesis " Vol 1-5, Academic Press, New York 1985.
M. Nogradi, "Stereoselective Synthesis" Verlag Chemie, Weinheim, 1987.
R. Noyori "Asymmetric Catalysis in Organic Synthesis", Wiley Interscience, 1994.
I. Ojima "Catalytic Asymmetric Synthesis", VCH, 1993.
R.S. Atkinson "Stereoselective Synthesis", John Wiley & Sons 1995.
R.E. Gawley and J. Aubé. “Principles of Asymmetric Synthesis” Tetrahedron Organic
Chemistry Series, Pergamon Press.
H.U. Blaser and E. Schmidt. “Asymmetric Catalysis on Industrial Scale”, Wiley.
Collins, A.N., Sheldrake, G.N.; Crosby J. (eds) "Chirality in industry: the commercial
manufacture and applications of optically active compounds" Vol. I y II, Wiley,
Chichester, 1992 y 1997.
Encyclopedias:
G. Helchem, R.W. Hoffmann, J. Mulzer, E. Shaumann ed. "Stereoselective Synthesis"
Houben-Weyl vol. 1-10 Georg Thieme Verlag, 1996, Stuttgart.
E.N. Jacobsen, A. Pfaltz, H. Yamamoto, ed. "Comprehensive Asymmetric Catalysis"
Vol 1-3, Springer, 1999.
H.B. Kagan "Asymmetric Synthesis using Organometallic Catalysis" en Comprehensive
Organometallic Chemistry, Vol. 8, Pergamon Press, Oxford, 1982