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CH264/1 Organic Chemistry II

Mechanism and Stereochemistry

Dr Andrew Marsh C515a.marsh@warwick.ac.uk

Dr David J Fox B510d.j.fox@warwick.ac.uk

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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

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Molecular shape and asymmetry

pp. 302 – 311 CGW 2/e

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Optical Activity

pp. 309 CGW 2/e

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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:

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C-I-P Assigning Priority

• We assign priority to the groups around the central atom according to atomic number

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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.

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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

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CGW p. 315

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

centre of inversion

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Examples

Mark stereogenic centres with *

Classify R or S

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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

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Chiral molecules without a stereogenic centre

ALLENES - axial chirality since the double bonds are hybridised at 90°

Biphenyls exhibit ATROPISOMERISMIf C-C rotation is restricted

CGW p. 319

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Helical ChiralityExamples 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).

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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

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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:

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Enantiotopic/ Diastereotopic Faces

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Examples

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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