CH 2641 Organic Chemistry II Mechanism and Stereochemistry

CH 264/1 Organic Chemistry II Mechanism and Stereochemistry Dr Andrew Marsh C 515 a. marsh@warwick. ac. uk Dr David J Fox B 510 d. j. fox@warwick. ac. uk 1 CH 264

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 2 nd Edition OUP 2012 2 CH 264

Molecular shape and asymmetry pp. 302 – 311 CGW 2/e 3 CH 264

Optical Activity pp. 309 CGW 2/e 4 CH 264

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: 5 CH 264

C-I-P Assigning Priority • We assign priority to the groups around the central atom according to atomic number 6 CH 264

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. 7 CH 264

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 8 CH 264

CGW p. 315 9 CH 264

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 10 CH 264

Examples Classify R or S Mark stereogenic centres with * 11 CH 264

Molecules without a stereogenic carbon atom Many atoms are stereochemically well-defined and thus can be considered as stereogenic. Examples include sulfur and phosphorous. Di. PAMP - an enantiopure hydrogenation catalyst R-methylphenyl sulfoxide 12 CH 264

Chiral molecules without a stereogenic centre ALLENES - axial chirality since the double bonds are hybridised at 90° CGW p. 319 Biphenyls exhibit ATROPISOMERISM If C-C rotation is restricted 13 CH 264

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). 14 CH 264

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 15 CH 264

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: 16 CH 264

Enantiotopic/ Diastereotopic Faces 17 CH 264

Examples 18 CH 264

Outputs 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. 19 CH 264