Stereochemistry 1. Stereoisomerism 2. Chirality Chapter 3 Stereochemistry 1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration 4. Acyclic Molecules with 2 or more stereocenters 5. Cyclic Molecules with 2 or more stereocenters 6. Properties of Stereocenters 7. Optical activity 8. Separation of Enantiomers, Resolution 9. Significance of Chirality in the biological world Lect 6, Sept 17, 2002 Lecture 6, Feb 11, 2003 Lecture 7 Fall 03 February 6 04 20 a c b

enantiomers diastereomers ISOMERISM constitutional same molecular formula, but different…. constitutional connectivity different stereoisomers - same connectivity different 3D orientation configurational isomers conformational isomers chair/boat Start of lecture 6, Sept 13 2001 enantiomers mirror images non-superposable diastereomers non-mirror images (cis/trans)

diastereomers trans cis

enantiomers e.g. Prozac - one isomer (“S”) is significantly more active

Chirality - right and left-handed substances - 2 spatial arrangements of atoms - analyze reflections (mirrors) same (achiral), different (chiral). mirror plane chiral -non-superposable, different arrangements in space

Elements of Symmetry Plane of symmetry: an imaginary plane passing through an object dividing it such that one half is the mirror image of the other half.

If symmetry element is present, Elements of Symmetry Conformations of 2,3-butanediol* syn - plane of symmetry anti - point of symmetry . . If symmetry element is present, substance is achiral *meso or R,S (later)

Elements of Symmetry Center of symmetry: a point situated so identical components of the object are located equidistant on opposite sides.

Chirality superposable mirror images - same compound rotate 180o superposable mirror images - same compound - a plane of symmetry - achiral

mirror images,  enantiomers Chirality-sp3 or tetrahedral center with 4 different groups = chiral molecule rotate e.g. (180o) see if images are superposable, e.g. Cl Cl Cl C F H Br C C H H F F Br Br Different, non-superposable mirror images,  enantiomers

enantiomers Tetrahedral - 4 different substituents (sp3) Cl C F Br H Stereocenter Stereogenic center - an atom that interchange of 2 groups gives a stereoisomer

Enantiomers R/S R S Lactic acid How do we distinguish chiral molecules? R S R/S

R,S Convention Priority rules Assign priority to each atom bonded to stereocenter. higher atomic number higher priority Increasing priority (7) -NH2 (8) -OH (17) -Cl (35) -Br (1) (6) -H -CH3

R,S Convention “Z” stereocenter, 4 gps. O > N > C > H 2. If same atoms bonded to the stereocenter, look to next set of atoms. Priority to the first point of difference. “Z” stereocenter, 4 gps. O > N > C > H 8 > 7 > 6 > 1

R/S absolute configuration of chiral compounds Rules: 1. Identify stereogenic center (C - 4 different gps.) 2. Assign priority to groups (C - 1, 2, 3, 4) 3. View C with “4” back; 1, 2, 3 FRONT 4. If 1>2>3 clockwise = R; counterclockwise = S 3 C 2 1 4 R

R & S configuration enantiomers R S

R,S Convention 3. Atoms in double (triple) bond viewed as equivalent number of single bonds (C is a stereogenic center) view as

S H^C priorities and assigning R/S 4 vs vs 1 H C H C 3 2 C H End lecture 6, sept 13, 2001

Assign R/S to the stereogenic center of the ester rotate 180o S

Assign R/S to stereogenic carbon in coniine Assign R or S to carvone S caraway/dill R spearmint Assign R/S to stereogenic carbon in coniine Golden pitcher plant R-(-)-coniine poison hemlock

Enantiomers & Diastereomers For a molecule with n stereocenters, a maximum of 2n stereoisomers “might” be possible. For a molecule with 1 stereocenter, 21 = 2 stereoisomers are possible. Start lecture 7, Sept 18, 2001 Start lecture 7, Sept 19, 2002 For a molecule with 2 stereocenters, a MAXIMUM of 22 = 4 stereoisomers might exist.

2n 256 (ignore sugar)

earlier R|S what about a second center? R - R R - S S - R S - S S R

* * Molecules with more than 1 stereocenter 22 = 4 trans-1-bromo-2-chlorocyclopropane * relative stereochemistry - both are ‘trans’ absolute stereochemistry - each is unique, enantiomers End of 6, start of lecture 7 R S (1R,2R)-1-bromo-2-chlorocyclopropane (1S,2S)-1-bromo-2-chlorocyclopropane

* * diastereomers diastereomers diastereomers enantiomers enantiomers Molecules with more than 1 stereocenter * trans-1-bromo-2-chlorocyclopropane 22 = 4 * cis-1-bromo-2-chlorocyclopropane (1S,2R)-1-bromo-2-chlorocyclopropane (1R,2S)-1-bromo-2-chlorocyclopropane diastereomers diastereomers diastereomers R S enantiomers enantiomers R S (1R,2R)-1-bromo-2-chlorocyclopropane (1S,2S)-1-bromo-2-chlorocyclopropane

Molecules with more than 1 stereocenter (1S,2R)-1-bromo-2-chlorocyclopropane (1R,2S)-1-bromo-2-chlorocyclopropane R S R S (1R,2R)-1-bromo-2-chlorocyclopropane (1S,2S)-1-bromo-2-chlorocyclopropane

Molecules with more than 1 stereocenter (1S,2R)-1-bromo-2-chlorocyclopropane (1R,2S)-1-bromo-2-chlorocyclopropane R S R S (1R,2R)-1-bromo-2-chlorocyclopropane (1S,2S)-1-bromo-2-chlorocyclopropane

2 or more stereocenters with symmetry leads to a meso isomer, superposable mirror images. Consider 2,3-dibromobutane: S S R R Lecture 7 September 19, 2002 S R S R

meso isomer is diastereomeric to enantiomers 2 or more stereocenters with symmetry leads to a meso isomer, superposable mirror images. Consider 2,3-dibromobutane: S R S R meso isomer is diastereomeric to enantiomers meso isomer S R R S only 3 realized part2