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Organic Chemistry Year 2 Mechanism and Stereochemistry Lecture 1


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CH264 Mechanism and Stereochemistry Lecture 1
Undergraduate Year 2 module on shape and reactivity of mostly organic molecules.

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Organic Chemistry Year 2 Mechanism and Stereochemistry Lecture 1

  1. 1. CH264 1 CH264/1 Organic Chemistry II Mechanism and Stereochemistry Dr Andrew Marsh C515 Dr David J Fox B510
  2. 2. CH264 2 Today’s Lecture 1. Cahn-Ingold-Prelog rules for stereochemical assignment 2. Enantiomers - molecules with one stereogenic centre 3. Diastereomers - molecules with two or more stereogenic centres 4. Chiral molecules without a stereogenic centre CGW = Organic Chemistry J Clayden, N Greeves, S Warren 2nd Edition OUP 2012
  3. 3. CH264 3 Molecular shape and asymmetry O O mirror plane spearmint caraway seed (-)-carvone (+)-carvone N NH O O O O H S-thalidomide N N H O O O OH mirror plane R-thalidomide sedative, hypnotic teratogenic anti-abortive pp. 302 – 311 CGW 2/e H H Cl Br H HCl Br mirror plane rotate 180° H H Br Cl IDENTICAL H H Cl Br rotate 180°
  4. 4. CH264 4 Optical Activity pp. 309 CGW 2/e polariser analyser (polarising filter)polarised light (electric field oscillating in one direction only) view optically active compound in solvent monochromatic light source
  5. 5. 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: a c b d re-draw a bc R stereochemistry
  6. 6. CH264 6 C-I-P Assigning Priority • We assign priority to the groups around the central atom according to atomic number Br H F Cl Br H F Cl view direction mirror Br FCl anticlockwise = S Br ClF clockwise = R view direction
  7. 7. 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. HO H CH2CH3 H3C OH H CH2CH3 CH3 view direction mirror OH CH2CH3H3C OH CH3H3CH2C view direction R S 1 23 1 2 3
  8. 8. 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..... Me OHEt * Me Cl HO O *+ Et Me O O Me Cl H+ CGW p. 311-315
  9. 9. CH264 9 Et Me O O Me Cl Et Me O O Me Cl R, S R, R Et Me O O Me Cl S, S Et Me O O Me Cl S, R enantiomers diastereomers diastereomers diastereomersdiastereomers CGW p. 315
  10. 10. CH264 10 meso-Compounds If a molecule has any symmetry element e.g. internal plane of symmetry, σ or centre of inversion, i, it is rendered optically inactive and is designated meso-. centre of inversion CO2HHO2C OHHO meso-tartaric acid CO2HHO2C HO OH CO2HHO2C HO OH (–)-tartaric acid(+)-tartaric acid HO2C CO2H OH OH HO2C CO2H OH OH R R S S S R HO2C CO2H OH OH m.p. 206°m.p. 168-170°m.p. 168-170° [α]D = +12° (water, 20°C) [α]D = –12° (water, 20°C) [α]D = 0° (water, 20°C)
  11. 11. CH264 11 Examples CH3 OH H Br F Cl Mark stereogenic centres with * Classify R or S Br CH3 OHC Br CO2H H
  12. 12. 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
  13. 13. CH264 13 Chiral molecules without a stereogenic centre ALLENES - axial chirality since the double bonds are hybridised at 90° Biphenyls exhibit ATROPISOMERISM If C-C rotation is restricted CGW p. 319
  14. 14. CH264 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).
  15. 15. 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 H3C O OH Ha Hb H3C O OH HO Hb transformation R-lactic acidpropionic acid CGW p. 820-823
  16. 16. 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 (1 H becomes 2 H for example) than the other and carry out the usual C-I-P ranking procedure: H3C O OH Ha Hb propionic acid Ha H3C O OH Ha > Hb Hb CH3 O HO pro-R pro-S Hb > Ha
  17. 17. CH264 17 Enantiotopic/ Diastereotopic Faces R1 O R2 NuNu OH R2 R1 Nu OH R2 R1 Nu R1 > R2 Re-face attack R2 > R1 Si-face attack X Y Z If X>Y>Z front as viewed is Re-
  18. 18. CH264 18 Examples HO F Ha Hb O H3C Cl N CH3 CH3 HO
  19. 19. CH264 19 You should be able to: (i) 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. Outputs