CH264/1 Organic Chemistry II Mechanism and Stereochemistry

1. CH264/1 Organic Chemistry IIMechanism and Stereochemistry Dr Andrew Marsh C515 a.marsh@warwick.ac.uk Dr David J Fox B510 d.j.fox@warwick.ac.uk CH264

2. Today’s Lecture • 1. Cahn-Ingold-Prelog rules for stereochemical assignment • 2. Enantiomers - molecules with one stereogenic centre • Diastereomers - molecules with two or more stereogenic centres • Chiral molecules without a stereogenic centre CGW = Organic Chemistry J Clayden, N Greeves, S Warren 2nd Edition OUP 2012 CH264

3. Molecular shape and asymmetry pp. 302 – 311 CGW 2/e CH264

4. Optical Activity pp. 309 CGW 2/e CH264

5. Assignment of stereochemistry • If an atom has four different groups around it, the centre is STEREOGENIC and the molecule will be CHIRAL • Cahn-Ingold-Prelog sequence rules (C-I-P) are used to assign stereochemistry to that centre • Revision: CGW p.308 If we assign a PRIORITY to these groups such that a>b>c>d and then re-draw the molecule such that the lowest priority (d) points away from us: CH264

6. C-I-P Assigning Priority • We assign priority to the groups around the central atom according to atomic number CH264

7. Assigning Priority 2 • Functional groups containing the same atom, look to the next substituent to decide priority. e.g. butan-2-ol • Use ‘single bond equivalents’ to decide which group takes priority. For example, a carbonyl group = 2 C-O bonds, an alkene = 2 C-C. CH264

8. Diastereomers • Chiral molecules with two stereogenic centres are called diastereomers. Diastereomers have different physical properties such as m.p., b.p. solubility etc. Hence they are separable by standard purification techniques, unlike enantiomers. • Certain pairs of diastereomers can be mirror images of each other and are thus enantiomers. • Consider the reaction of butan-2-ol with 2 chloropropanoic acid..... CGW p. 311-315 CH264

9. CH264 CGW p. 315

10. meso-Compounds If a molecule has any symmetry element e.g. internal plane of symmetry, s or centre of inversion, i, it is rendered optically inactive and is designated meso-. centre of inversion CH264

11. Examples Classify R or S Mark stereogenic centres with * CH264

12. Molecules without a stereogenic carbon atom Many atoms are stereochemically well-defined and thus can be considered as stereogenic. Examples include sulfur and phosphorous. DiPAMP - an enantiopure hydrogenation catalyst R-methylphenyl sulfoxide CH264

13. Chiral molecules without a stereogenic centre Biphenyls exhibit ATROPISOMERISM If C-C rotation is restricted ALLENES - axial chirality since the double bonds are hybridised at 90° CH264 CGW p. 319

14. Helical Chirality Examples of helical molecules include hexahelicene which can be resolved into two enantiomers. When viewed from above, the right handed helix is described as P (plus) and the left handed helix is called M (minus). CH264

15. Enantio/ diasterotopicity A PROCHIRAL centre is one that can become stereogenic if one group is replaced by a new, different one: Ha and Hb are HETEROTOPIC and can be assigned C-I-P prochirality descriptors CGW p. 820-823 CH264

16. Classification of prochiral centres We simply use an extension of the Cahn-Ingold-Prelog rules for stereochemical nomenclature to designate the heterotopic atoms pro-R or pro-S. We choose each of the two atoms in turn giving it higher priority (1H becomes 2H for example) than the other and carry out the usual C-I-P ranking procedure: CH264

17. Enantiotopic/ Diastereotopic Faces CH264

18. Examples CH264

19. Outputs You should be able to: Use R/S configuration according to C-I-P nomenclature. (ii) Define and use the terms enantiomer and diastereomer. (iii) Recognise non-carbon atom stereogenic centres. (iv) Define axial and helical chirality and give examples. (v) Identify and use prochiral centres and faces. CH264