CHM 136 H Stereochemistry Chapter 5 excluding 5.3, 5.4, 5.10, 5.12 Chapter 25: 25.2 only McMurry, 9th edition 1 Chapter 7: 7.4, 7.5 Isomers Different compounds with the same molecular formula Constitutional isomers: isomers with different atomic connectivities Stereoisomers: isomers with the same atomic connectivity but with different geometries O OH H Br H Br H Br Br H 2 1 2 McMurry 9th Ed., Section 7.5 Di-substituted alkenes can be named cis or trans: Cahn-Ingold-Prelog rules for naming alkenes First, a brief look at alkene stereochemistry cis trans We need rules for naming tri- and tetra-substituted alkenes 3 Tri- and tetra-substituted alkenes Two stereoisomers: Z: the two groups of higher priority are on the same side of the double bond E: the two groups of higher priority are on the opposite side of the double bond We determine priority with the Cahn-Ingold-Prelog rules 4 3 4 The Cahn-Ingold-Prelog rules 1. Rank atoms on each end of the double bond in decreasing atomic number Br > Cl > F > O > N > C … > H 2. If the first atoms in the substituent are the same, look at the 2nd, the 3rd, the 4th, …., until the first difference is found 5 3. Multiple-bonded atoms are equivalent to same number of single bonded atoms E.g. when you see: prioritize using: 6 5 6 mirror The mirror image: Chirality = “handedness” objects that do not have a mirror plane are CHIRAL objects that contain a mirror plane are ACHIRAL 7 8 Properties of chiral objects A chiral object and its mirror image cannot be superimposed achiral: can be superimposed 9 chiral: cannot be superimposed Molecules that possess a mirror plane are ACHIRAL. mirror plane Some molecules are achiral, some are chiral: 9 10 11 Chiral molecules cannot be superimposed on their mirror image Some molecules are achiral, some are chiral: A chiral molecule: mirror plane Some molecules are achiral, some are chiral: 12 Which are chiral and which are achiral 11 12 Chiral molecules and their non-superimposable mirror images are called “enantiomers” chiral enantiomers The chirality often originates from a tetrahedral carbon atom that is bonded to four different substituents. Such a carbon centre is called a “chirality centre” or “stereocentre” chirality centre 13Molecules with odd numbers of chirality centres are chiral. Biology is full of chiral molecules alanine: sucrose (table sugar): chiral chiral 14 13 14 Which of the following drugs is/are chiral Where are the chirality centres Aspirin Tylenol Advil (acetaminophen) (ibuprofen) 15 melting point: So how can enantiomers be differentiated from each other 2. optical activity 1. interactions with other chiral molecules/environments 112 °C 91 °C 1.255 g/mL S R e.g. 2-bromobutane density:boiling point: Enantiomers have identical physical properties 16 15 16 1. interactions with other chiral molecules/environments E.g. many biological receptor sites are chiral – will only “accept” one particular enantiomer of a substance – biological molecules often have different tastes, smells, toxicities 17 (+)-carvone smells like caraway (-)-carvone smells like spearmint 2. optical activity chiral molecules are optically active – they rotate plane-polarized light one enantiomer rotates light to the right = (+) or d-enantiomer other enantiomer rotates light to the left = ( ) or l-enantiomer (S)-(+)-lactic acid (R)-(–)-lactic acid observeranalyzerpolarizer sample tube light source unpolarized light polarized light 18 17 18 – optically active compounds must be chiral: 19 one enantiomer rotates light to the right = (+) or d-enantiomer other enantiomer rotates light to the left = ( ) or l-enantiomer (S)-(+)-lactic acid (R)-(–)-lactic acid – equal concentrations of enantiomers will rotate light in opposite directions by the same amount: e.g. 1.00 g/mL (R)-( )-lactic acid: = 3.82° 1.00 g/mL (S)-(+)-lactic acid: = +3.82° 1.00 g/mL (S)-2-bromobutane: = +23.1° 1.00 g/mL 2-bromo-2-methylbutane: = 0.0° Indicating chirality – how to indicate the different configuration of substituents around each chirality centre 1. Identify the chirality centre lactic acid 19 20 2. Determine the priorities of attached groups 3. Rotate molecule to put the lowest priority group at the back H at the back behind C the Cahn-Ingold-Prelog rules left hand turn (anti-clockwise) lactic acid Its enantiomer: (S)- 1 2 3 right hand turn (clockwise) “R” and “S” are the (absolute) configurations of a chirality centre 4. Determine direction from 1st to 2nd to 3rd priority groups 2 1 3 lactic acid(R)- Easy to remember! R = “right” 21 22 REVIEW: determining group priorities: the Cahn-Ingold-Prelog rules 2. If the first atoms in the group are the same, look at the 2nd, the 3rd, the 4th …., 1. Rank atoms attached to the chirality centre in decreasing atomic number: Br > Cl > F > O > N > C … > H 3. Multiple-bonded atoms equivalent to same number of single bonded atoms When you see: prioritize using: When you see: prioritize using: 25 24 25 Let’s try some examples 26 Assign absolute configuration to the chirality centres in the following molecules. 27 Artemisinin (anti-malaria drug) 2015 Nobel Prize in Physiology or Medicine R R S R SS R 26 27 both C2 and C3 can be either R or S threonine Molecules with >1 chirality centre For n chirality centres, a maximum of 2n stereoisomers exist. 2 3 28 – two stereocentres Four stereoisomers are possible: 2R,3R 2R,3S 2S,3R 2S,3S e.g. (2S,3R)-2-amino-3-hydroxybutanoic acid – configuration is given in parentheses at the front of the name: S SR R SR SR The four possible stereoisomers 29 enantiomers – must have opposite configuration at ALL chirality centres Non superimposable mirror images diastereomers – configuration not opposite at all chirality centres NOT mirror images! 28 29 D-glucoseD-galactose R Diastereomers have different physical and chemical properties e.g. boiling point, spectra, solubility, etc….. R S S m.p. = 167oC m.p. = 146oC R R R S D-mannose m.p. = 133oC S R R S E.g. tartaric acid = meso compound A molecule can have chirality centres but still be achiral RS RS meso compounds have an internal mirror plane RS The molecule and its mirror image are superimposable = achiral RRSS Its other two stereoisomers are enantiomers 31 30 31 Fischer projections (Section 25.2) Fischer represented chirality centres differently: Fischer projection 1852-1919 Emil Fischer the molecule appears flat central C atom is not shown horizontal lines out of the page vertical lines into the page 32 – two (or more) chirality centres: R,R-tartaric acid normally, the longest carbon chain is drawn vertically R R COOH COOH OH HO H Hrotate the vertical line connecting the two middle chirality centres lies in the plane of the page all other vertical lines go into the page 33 32 33 Fischer projections can be rotated according to certain rules 34 180o same as keeping one group fixed and rotating the others How are Fischer projections useful – helpful for visualizing molecules with two or more chirality centres e.g. sugars and sugar derivatives CH=O OH OH OH HO H H H H CH2OH by convention, the carbon with the higher oxidation state is put at the top D-glucose COOH COOH OH HO H H – it is easy to draw mirror images COOH COOH H H OH HO R,R tartaric acid S,S 35 34 35 Practice 36 Draw Fischer projections of all of the isomers of 2,3-dichlorobutane. What is the relationship between the isomers Prochirality An achiral molecule is prochiral if, in a single chemical step, it can be converted into a chiral product. H2 2-butanone 2-butanol prochiral chiral 37 36 37 H2 Stereochemical result of prochirality 2-butanone prochiral and clockwise = re face counterclockwise = si face racemic mixture! Trigonal planar atoms can have prochiral faces: or si face re face H H Stereochemical Result of Prochirality (S)-2-Butanol (R)-2-Butanol “re” and “si” refer to the reactant, NOT the product!! 38 39 Defining pro-R and pro-S substituents: 1. Raise the priority of the atom of interest over the other (identical) atom without changing the priority relative to the other substituents 2. Use the usual method to determine the configuration of the chirality center prochiral centre ” ” ” ” 12 3 4 Tetrahedral atoms can be prochiral centres: Practice 41 Label the relevant hydrogen atoms in sec-butanol as pro-R and pro-S. 40 41 Summary isomersconstitutional Isomers different connectivity Enantiomers Non superimposable mirror images same connectivity stereoisomers Diastereomers Non superimposable non mirror images cis – trans diastereomers (E/Z) 42 meso compounds Superimposable mirror images RS 42
