Chapter 5 Stereoisomerism and Chirality

Donald Cram Source: Michigan State University, Department of Chemistry http://www.chemistry.msu.edu/Portraits/PortraitsHH_collection.shtml

Chapter 5 Skip p. 388-389 Read p. 475-477 for interest Don’t memorize names of sugars (p. 460-465) or amino acids (p. 472-474)

Chapter 5 Problems 1 a, b, c, e, g, m 2 4 a, b, c, d, f, g, i 5 a, b, e 11, 12 13 b, c, d 14 - 18 20 a, b, d 23 - 28 30 32 - 36 38 40, 41 43 45 48 52 59

Sect 5.1: Symmetry and Chirality If a molecule is superimposable on its mirror image, it is achiral (non-chiral). If a molecule is not superimposable on its mirror image, it is chiral. Enantiomers are isomers that are non-superimposable mirror-images

Sect 5.2: Enantiomers Four different atoms are attached to a chiral carbon atom. Mirror images are non-superimposable. rotate this molecule is chiral note that the fluorine and bromine have been interchanged in the enantiomer

Stereocenters The previous molecule has a stereocenter, and is chiral. A stereocenter is an atom, or a group of atoms, that can potentially cause a molecule to be chiral. stereocenters - can give rise to chirality

An achiral molecule A carbon atom with three identical groups is achiral! There is a symmetry plane in the plane of the paper.

plane of symmetry C l C l C l C l B r C l B r C l side view edge view

Another achiral molecule This molecule has a plane of symmetry in the plane of the paper. These two structures are superimposable!

Look for carbon atoms with four different groups! Sect 5.3: identification of stereocenters Look for carbon atoms with four different groups! * *

* * *

Finding stereocenters * plane ( indicates no stereoisomers )

Finding stereocenters * * * * * * The cis isomer (two methyl groups) - achiral! Thetrans isomers has two stereocenters!

Finding stereocenters * * * * * * * * n = 8 28 = 256

Sect. 5.4 Properties of Enantiomers Enantiomers interact differently with polarized light. Enantiomers have equal magnitude, but opposite signs of rotation Most other properties are identical. Odor may be different!!

Sect. 5.5 Polarimetry dissolve sample in a solvent and put sample into polarimeter obtain sign of rotation value depends on concentration and path length.

Optical Activity

(+)- d- Dextrorotatory (-)- l- Levorotatory TYPES OF OPTICAL ACTIVITY new older (+)- d- Dextrorotatory Rotates the plane of plane-polarized light to the right. new older (-)- l- Levorotatory Rotates the plane of plane-polarized light to the left.

Specific Rotation [a]D This equation corrects for differences in cell length and concentration. a [a]D = t cl Specific rotation calculated in this way is a physical property of an optically active substance. a = observed rotation You always get the same c = concentration ( g/mL ) [a]D t value of l = length of cell ( dm ) D = yellow light from sodium lamp t = temperature ( Celsius )

ENANTIOMERS HAVE EQUAL VALUES BUT OPPOSITE SIGNS OF ROTATIONS W W Enantiomers C C Y X X Y Z Z (+)-numbero (-)-numbero dextrorotatory levorotatory The numbers are the same, but have opposite signs. All other physical properties are IDENTICAL.

Racemic mixture [a]D = 0o an equimolar (50/50) mixture of enantiomers the effect of each molecule is cancelled out by its enantiomer

Sect. 5.6 Configuration Arrangement in space of atoms or groups around the stereocenter of the molecule Enantiomers have different configurations.

Sect. 5.7 Specification of Configuration: Cahn-Ingold-Prelog rules

Sir Christopher Ingold Source: Michigan State University, Department of Chemistry http://www.chemistry.msu.edu/Portraits/PortraitsHH_collection.shtml

Specification of Configuration SEQUENCE RULE 1: priority depends on the atomic numbers of the 4 atoms attached to the stereocenter; atom with higher atomic number receives the higher priority. If two atoms are isotopes of the same element, the heavier isotope is assigned the higher priority.

R S

Specification of Configuration SEQUENCE RULE 2: If the relative priority of two groups cannot be decided by Rule 1, it shall be determined by a similar comparison of the next atoms in the groups (and so on, if necessary), working outward in ranks from the stereocenter.

Specification of Configuration SEQUENCE RULE 3: A doubly-bonded atom A is treated as if there were two C-A single bonds. Priorities in the expanded representations are assigned on the basis of Rule 2.

Remember! The atoms shown in parentheses (the duplicate representations) do not exist! They are written only for purposes of assigning priorities.

More... A triply-bonded atom A is treated as if there were three C-A bonds, as in:

Corollary of Rule 3 If no other distinction can be made, a real atom outranks a “fictional” atom. NOTE CAREFULLY: This exception is used only as a last resort! You will rarely see this happen.

Sect. 5.8: Compounds with more than one stereocenter: 3-Chloro-2-butanol

Fischer formulas (Sect. 5.9) 3- Chloro-2-butanol: Fischer formulas (Sect. 5.9) pair of enantiomers-1 pair of enantiomers-2 diastereomers

How Many Stereoisomers Are Possible? maximum number of stereoisomers = 2n, where n = number of stereocenters sometimes fewer than this number will exist For the previous example; two stereocenters = 4

Determining the number of possible stereoisomers * * 22 = 4 stereoisomers * * * 23 = 8 stereoisomers

2,3-Dichlorobutane mirror image is identical S R meso diastereomers S enantiomers

2,3-Dichlorobutane meso

Fischer formulas (Sect. 5.9) 2,3-Dichlorobutane: Fischer formulas (Sect. 5.9) Meso! “Pair” becomes one! pair of enantiomers diastereomers

Tartaric Acid (from fermentation of wine): There are three stereo-isomers ALSO FOUND (as a minor component) [a]D = 0 meso -tartaric acid

Sect 5.9: Fischer Formulas

EVOLUTION OF THE FISCHER PROJECTION C H O O H H O C H C H O C H O H O “Sawhorse” Projection EVOLUTION OF THE FISCHER PROJECTION C H O O H H O C 2 H Fischer Projection Orient the main chain vertically with the most oxidized group at the top. C H O C H O H O H H O H C H 2 O C H O H 2 Substituents will stick out toward you like prongs Main chain bends away from you

OPERATIONS WITH FISCHER PROJECTIONS Mirror images (enantiomers) are created by switching substituents to the other side. enantiomers diastereomers All stereocenters must be switched to get an enantiomer (the mirror inverts them all). If you switch only one of the stereocenters, but not both, you get a diastereomer.

. Legal operations with Fischer formulas Rotation by 180o in the plane of the paper does not change the molecule. No other rotation is allowed.

This molecule is meso! There isn’t an enantiomer The molecule does not have an enantiomer because it is not chiral. It had a plane of symmetry, rendering it a meso molecule. plane of symmetry

R CHO H H O H OHC C H O H C H O H O H R O H CHO R HOCH2 CHO H O H H C To determine the configuration (R/S). Make two “switches”. Place the priority 4 group in one of the vertical positions. 2 4 #4 at top position CHO H 1 H O H OHC C H O H 4 2 2 3 C H O H O H R 2 3 1 Both H’s are in back = same result alternatively: 1 2 O H R CHO R 3 2 1 HOCH2 CHO H O H 4 H C H O H 2 4 3 #4 at bottom position

Draw all of the stereoisomers!

Any more?? NO!

There are only four stereoisomers!

Sect 5.10: cyclic compounds

* stereoisomers (max) : 20 = 1 21 = 2 21 = 2 plane ( indicates no stereoisomers ) stereoisomers (max) : 20 = 1 21 = 2 21 = 2

* * * * * * stereoisomers (max) : 22 = 4 22 = 4 22 = 4 plane ( but only if cis ) stereoisomers (max) : 22 = 4 22 = 4 22 = 4

1-Bromo-2-chlorocyclopropane note that the cis/trans isomers are also diastereomers R S R S cis enantiomers diastereomers R R S S trans enantiomers

1,2-Dibromocyclopropane mirror image identical B r Br Br B r cis meso diastereomers B r B r trans Br Br enantiomers

1-Bromo-2-chlorocyclohexane cyclohexanes may be analyzed using planar rings cis enantiomers diastereomers trans enantiomers

1,2-dichlorocyclohexane mirror image identical cis meso diastereomers trans enantiomers

Interchanges: See problem 59 ONE STEREOCENTER CH3 CH3 C C H H Br F F Br enantiomer Odd: 1..3..5…etc interchanges = enantiomer Even: 2..4..6...etc interchanges = original compound

You can use interchanges to answer this question! Next slide. PROBLEM: ARE THESE IDENTICAL OR ARE THEY ENANTIOMERS? CH3 H C C CH3 H F Br Br F You can use interchanges to answer this question! Next slide.

C CH3 Br F H ENANTIOMER SAME 1 2 3

They are enantiomers! Three switches = enantiomers Back to the problem: are these identical or are they enantiomers? CH3 H C C CH3 H F Br Br F They are enantiomers! Three switches = enantiomers

MORE THAN ONE STEREOCENTER To form an enantiomer you must interchange all of the stereocenters. enantiomer two stereocenters two interchanges

If a compound has more than one stereocenter, and you only interchange one of them, you willI form a distereomer. two stereocenters one interchange diastereomer

Sect 5.11: Stereocenters other than carbon

Sect 5.12: Other types of chirality

Sect 5.13: Resolution (Skip)

Sect 5.14-5.16: carbohydrates

Emil Fischer Source: Michigan State University, Department of Chemistry http://www.chemistry.msu.edu/Portraits/PortraitsHH_collection.shtml

Glyceraldehyde (an aldotriose)

Notice that the D enantiomer has the R configuration in the R/S sytem.

The Aldotetroses Notice that the D enantiomers are (-)! Notice that the L Enantiomers are (+)!

There is no relationship between D or L and the sign of rotation in a polarimeter! D can either be (+) or (-) L can either be (+) or (-)

Fig. 5-27: the aldopentoses

There are four natural pentose sugars. They have the D configuration. OH points to right! D OH points to right! D OH points to right D OH points to right D

Fig 5-28 “natural” D-aldohexoses

The “unnatural” L-aldohexoses

Sect 5.17: natural products and amino acids

(R) (S) Amino acids belong to the L-series. Can You assign the R or S configuration to the following Fischer structure of Alanine? Same! enantiomer (R) The original structure is, therefore, (S)

These compounds are enantiomers! They have identical physical properties, except for odor and rotation of light in a polarimeter!