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CH264/1 Organic Chemistry II Mechanism and Stereochemistry. Dr Andrew Marsh C515 a.marsh@warwick.ac.uk Dr David J Fox B510 d.j.fox@warwick.ac.uk. Today ’ s Lecture. 1. Cahn-Ingold-Prelog rules for stereochemical assignment 2. Enantiomers - molecules with one stereogenic centre
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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
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
Molecular shape and asymmetry pp. 302 – 311 CGW 2/e CH264
Optical Activity pp. 309 CGW 2/e CH264
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
C-I-P Assigning Priority • We assign priority to the groups around the central atom according to atomic number CH264
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
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
CH264 CGW p. 315
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
Examples Classify R or S Mark stereogenic centres with * CH264
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
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
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
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
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
Examples CH264
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