Unit One Part 8: stereochemistry

Transcription

1 Unit ne Part 8: stereochemistry 1 Describe the difference between stereoisomers & structural isomers omenclature used for double bonds (cis-trans or E-Z) Predict conformations of cyclohexanes Define chirality and recognise stereocentres Understand enantiomers and diastereoisomers dr gareth rowlands; g.j.rowlands@massey.ac.nz; science tower a4.12

2 Isomerism 2 different bond pattern structural isomers ISMERS diastereomers stereoisomers same bond pattern non-superimposable mirror images Structural isomers enantiomers (E)-pent-3-en-1-ol 5 10 cyclopentanol methoxybut-1-ene methylbutan-2-one 5 10 (S)-pent-1-en-3-ol 5 10

3 onfigurational isomerism or stereoisomerism 3 The spatial arrangement of atoms in a molecule is its configuration onfigurational isomers have the same bonds onfigurational isomers can only be interconverted by breaking a bond Easiest compounds to see this in are the alkenes... A D B D A B Atom connectivity identical But different configurations Known as diastereoisomers They are different compounds 2 dimethyl fumarate trans (E) mp 103 bp 193 dimethyl maleate cis (Z) mp 19 bp 202 R R R R E or trans less stable steric crowding Z or cis

4 E and Z nomenclature E-alkenes have the highest priority groups on the opposite sides Z-alkenes have the highest priority groups on the same side Priority rules 1. Rank atoms attached to alkene in order of decreasing atomic number atom = Br>l>>>> Atomic number = 35, 17, 8, 7, 6 & 1 2. If atoms are the same, move along substituent until a difference is found 2 > > Multiple bonds are assumed to count as the same number of single bonds l (Z)-2-chloro-3- methylpent-2-ene 2 Ph (Z)-3-hydroxymethyl-4-oxo-2- phenylbut-2-enoic acid Br 2 3 (E)-2-bromo-3- (hydroxymethyl) pent-2-enenitrile (E)-3-methyl-4- phenylpent-3-en-2-one 2 1

5 is trans isomerism in cyclohexanes 5 l l l l l cis-1,2- dichlorocylohexane (syn) l trans-1,2- dichlorocylohexane (anti) If two groups on a ring we must specify relative stereochemistry is - both groups are on the same face Trans - groups are on opposite faces l trans-1,2- dichlorocylohexane (anti) l cis-1,2- dichlorocylohexane (syn) 1 l 2 l 2 l both conformations have one axial substituent & are identical 1 l 2 l X 2 l 1 l 1 l one conformation is disfavoured as it has two axial groups so maximum 1,3-diaxial interactions t Bu bulky group equatorial favoured t Bu tert-butyl group rarely is axial

6 Decalins 6 trans-decalin equatorial, equatorial ring fusion cis-decalin equatorial, axial ring fusion Another example of stereoisomers comes from fused bicyclic molecules Like a double bond the substituents could be cis or trans Like a double bond these two are not interconvertible unless a bond broken

7 hirality 7 Mirror image Left & right hands on-superimposable The most confusing form of stereochemistry A chiral structure is one that is non-superimposble on its mirror image ccurs in nature (snails, honeysuckle etc), man-made objects (propellers, corkscrews etc) and in molecules...

8 Enantiomers 8 This form of stereoisomerism arises from a lack of symmetry The molecule & its mirror image are different The molecule & its mirror image are known as enantiomers Achiral Mirror plane hiral Mirror plane rotate X X For those of a sick & twisted disposition more info on chirality & stereochemistry can be found at my website:

9 Enantiomers II Most common form of chirality has a carbon atom with 4 different groups attached & is called central chirality 9 2 Ph Et darvon painkiller (R)-thalidomide (morning sickness) nicotine toxin / stimulant 2 2 L-alanine mammalian amino acid Many other forms of chirality including helical, axial & planar PPh 2 PPh 2 Ph Ph 2 P Fe (R)-(+)-BIAP (R)-2-(diphenylphosphino)-1-(2-(diphenyl phosphino)naphthalen-1-yl)naphthalene M-[8]helicene (R)-2-phenyl-1- (diphenylphosphanyl) ferrocene

10 Physical properties of enantiomers Enantiomers have identical physical properties such as mp, bp etc They only differ in their interactions with other chiral entities 10 α Ph 2 (R)-(-)-mandelic acid [α] D light source light (λ) polariser plane polarised light sample cell length l (dm) reading Ph 2 (S)-(+)-mandelic acid [α] D hiral compounds rotate the plane of polarised light (hence optical isomers) As most biological systems are chiral, enantiomers can have different effects (R)-carvone spearmint (S)-carvone caraway (S)-limonene lemons (R)-limonene oranges

11 Two chiral centres (diastereoisomers) Mirror 11 S R Two enantiomers differ by absolute configuration 2 2 A molecule with 1 stereogenic centre exists as 2 enantiomers Enantiomers have identical physical properties in an achiral environment A molecule with 2 stereogenic centres can exist as 4 stereoisomers Enantiomers (mirror images) still have identical physical properties Diastereoisomers (non-mirror images) have different properties enantiomers trans epoxide mp = 141 diastereoisomers different mp enantiomers cis epoxide mp =

12 hirality in our bodies alanine phenylalanine histidine ommon amino acids are all have the same stereochemistry (L or S) Aspartame (sweetener) is a dipeptide (two amino acids) - two stereocentres Potentially 4 compounds (n stereocentres can give 2 n diastereoisomers) Insulin is made of 2 peptide chains - 1x30 amino acids & 1x21 amino acids Potentially 2.25 x diastereoisomers A relatively small protein is ribonuclease at 124 amino acids or Potentially 2.13 x diastereoisomers

13 hiral drugs 13 Et Et Et Et Ethambutol tuberculostatic (anti-tb) (R,R)-enantiomer causes blindness ( )-propanolol β-blocker for heart disease (+)-propanolol contraceptive S (S)-timolol high blood pressure (R)-timolol glaucoma S

14 verview 14 What have we learnt? Molecules are three dimensional...and it makes a difference The arrangement of atoms in space can form new isomers Such isomers can only be interconverted by breaking bonds Mirror images can have very different properties Synthesis of single enantiomers is very important What's next? A brief look at spectroscopy in many of its glorious forms Starting with MR or nuclear magnetic resonance spectroscopy An idea of what information this tells us about protons in a molecule dr gareth rowlands; g.j.rowlands@massey.ac.nz; science tower a4.12