StereochemistryStereochemistryThe study of the three The study of the three

dimensional structure of dimensional structure of molecules.molecules.

Isomers—A reviewIsomers—A review Constitutional/Structural Isomers:Constitutional/Structural Isomers: differ in differ in

their bonding sequence; their atoms are their bonding sequence; their atoms are connected differently.connected differently.

Stereoisomers:Stereoisomers: have the same bonding have the same bonding sequence, but differ in the orientation of sequence, but differ in the orientation of their atoms in space. One special type of their atoms in space. One special type of stereoisomerism that you have seen is stereoisomerism that you have seen is geometric isomerism (e.g. cis/trans geometric isomerism (e.g. cis/trans isomers).isomers).

ChiralityChirality Chiral:Chiral: a chiral object is one that has right and a chiral object is one that has right and

left handed forms, or a left handed forms, or a nonsuperimposable nonsuperimposable (nonidentical) mirror image. A chiral object has (nonidentical) mirror image. A chiral object has a mirror image that is different from the a mirror image that is different from the original object. An object that is not chiral is original object. An object that is not chiral is described as “described as “achiralachiral”.”.

An atom is chiral only if it has An atom is chiral only if it has four different four different groups attached to it.groups attached to it.

The mirror image of a chiral molecule is called The mirror image of a chiral molecule is called its its enantiomerenantiomer. .

Do problems 5-1, 5-2 and 5-3 in the text.Do problems 5-1, 5-2 and 5-3 in the text.

Chiral Molecules vs. Chiral CentersChiral Molecules vs. Chiral Centers A molecule with one chiral center is a chiral A molecule with one chiral center is a chiral

molecule.molecule. A molecule with more than one chiral center A molecule with more than one chiral center

is achiral if it has a plane of symmetry.is achiral if it has a plane of symmetry. Enantiomers have identical physical Enantiomers have identical physical

properties (e.g. bp, mp, density) except that properties (e.g. bp, mp, density) except that they rotate plane polarized light in equal but they rotate plane polarized light in equal but opposite directions. They are said to possess opposite directions. They are said to possess “optical activity” or to be “optically active”. “optical activity” or to be “optically active”. Achiral molecules are not optically active! Achiral molecules are not optically active!

Do problem 5-4 in the text.Do problem 5-4 in the text.

H

BrH

Br Br

HH

Br

chiral achiral

Chiral: does not containChiral: does not containa plane of symmetrya plane of symmetry

Achiral: contains aAchiral: contains aplane of symmetryplane of symmetry

Optical ActivityOptical Activity Optical Activity is measured with a Optical Activity is measured with a polarimeter.polarimeter. A compound in a polarimeter can rotate plane A compound in a polarimeter can rotate plane

polarized light to the right or left by a specific polarized light to the right or left by a specific number of degrees that must be determined number of degrees that must be determined experimentally. Compounds that rotate plane experimentally. Compounds that rotate plane polarized light to the right (clockwise) are polarized light to the right (clockwise) are called called dextrorotatory (dextrorotatory (dd),), and compounds that and compounds that rotate plane polarized light to the left (counter-rotate plane polarized light to the left (counter-clockwise) are called clockwise) are called levorotatory (levorotatory (ll).). In IUPAC In IUPAC notation, this is abbreviated by the signs notation, this is abbreviated by the signs (+)(+) and and (-)(-) respectively. respectively.

Nomenclature of Chiral Carbon Nomenclature of Chiral Carbon AtomsAtoms

The configuration about chiral carbons is The configuration about chiral carbons is named using the named using the Cahn-Ingold-PrelogCahn-Ingold-Prelog convention, which assigns to each chiral convention, which assigns to each chiral carbon atom a letter (carbon atom a letter (RR) or () or (SS).).

Cahn-Ingold-Prelog Rules:Cahn-Ingold-Prelog Rules:

Assign a priority to each group bonded to the Assign a priority to each group bonded to the chiral carbon. The higher the atomic number chiral carbon. The higher the atomic number of the atom, the higher its priority. With of the atom, the higher its priority. With different isotopes of the same element, the different isotopes of the same element, the heavier isotopes have higher priority. When heavier isotopes have higher priority. When there is a tie, use the next atoms along the there is a tie, use the next atoms along the chain as tiebreakers. Treat double and triple chain as tiebreakers. Treat double and triple bonds as if each were bonded to a separate bonds as if each were bonded to a separate atom.atom.

Using a three dimensional drawing or a model, Using a three dimensional drawing or a model, put the fourth priority group in the back and put the fourth priority group in the back and view the molecule along the bond from the view the molecule along the bond from the chiral carbon to the fourth priority group. chiral carbon to the fourth priority group. Draw an arrow from the first priority group, Draw an arrow from the first priority group, through the second, to the third. If the arrow through the second, to the third. If the arrow points clockwise, the chiral atom is called (points clockwise, the chiral atom is called (RR). ). If the arrow points counterclockwise, the If the arrow points counterclockwise, the chiral atom is called (chiral atom is called (SS).).

Cahn-Ingold-Prelog RulesCahn-Ingold-Prelog Rules

Do problem 5-5 in the text.Do problem 5-5 in the text.

Biological Discrimination of Biological Discrimination of EnantiomersEnantiomers

Enantiomers can be distinguished through the Enantiomers can be distinguished through the use of use of chiral probeschiral probes. A polarimeter is one . A polarimeter is one example of a chiral probe. example of a chiral probe. EnzymesEnzymes are a type are a type of chiral probe that are found in living systems. of chiral probe that are found in living systems. In general, just one out of a pair of In general, just one out of a pair of enantiomers produces the characteristic enantiomers produces the characteristic effect; the other either has a no effect or has a effect; the other either has a no effect or has a totally different (and sometimes toxic) effect.totally different (and sometimes toxic) effect.

Do problem 5-10 in the text.Do problem 5-10 in the text.

Racemic MixturesRacemic Mixtures A mixture that contains equal amounts of a A mixture that contains equal amounts of a

pair or enantiomers is called a pair or enantiomers is called a racemic racemic mixturemixture or a or a racemateracemate, a , a (±)(±) pair, or a pair, or a ((d,ld,l)) pair. A racemic mixture is symbolized by pair. A racemic mixture is symbolized by placing (±) or (placing (±) or (d,ld,l) in front of the name of ) in front of the name of the compound.the compound.

Racemic mixtures are optically inactive.Racemic mixtures are optically inactive. Since the enantiomers rotate plane Since the enantiomers rotate plane polarized light in equal but opposite polarized light in equal but opposite directions, the net result is an optical directions, the net result is an optical rotation of zero.rotation of zero.

Enantiomeric ExcessEnantiomeric ExcessWhen a mixture of enantiomers is neitherWhen a mixture of enantiomers is neitherenantiomerically pure (all one enantiomer)enantiomerically pure (all one enantiomer)nor racemic (equal amounts of two nor racemic (equal amounts of two enantiomers), the relative amounts of the enantiomers), the relative amounts of the enantiomers in the mixture can be expressedenantiomers in the mixture can be expressedas the enantiomeric excess (optical purity).as the enantiomeric excess (optical purity).

e.e. d - l x 100

(excess of one over the other)(entire mixture)

= d + l

= x100

Chiral Compounds Without Chiral AtomsChiral Compounds Without Chiral Atoms

Biphenyls: some ortho substituted biphenyls are Biphenyls: some ortho substituted biphenyls are locked into one of two chiral, enantiomeric locked into one of two chiral, enantiomeric staggered conformations.staggered conformations.

There are some molecules that do not contain chiral There are some molecules that do not contain chiral carbons but are chiral. carbons but are chiral.

I

BrBr

I I

Br

Br

I

Staggered conformationStaggered conformation(chiral)(chiral)

Staggered conformationStaggered conformation(chiral)(chiral)

C C C

H

H3C

H

CH3

C C C

H

CH3

H

H3C

Chiral compounds without chiral atomsChiral compounds without chiral atoms

••Allenes: Compounds containing a C=C=C unit are Allenes: Compounds containing a C=C=C unit are

called called allenesallenes. In allene, the central C atom is sp . In allene, the central C atom is sp hybridized, but the two outer carbons are sphybridized, but the two outer carbons are sp22. The whole . The whole

molecule does not lie in the same planemolecule does not lie in the same plane. An allene is. An allene ischiral if each end has two distinct chiral if each end has two distinct substituents.substituents.

Enantiomers of 2,3-pentadieneEnantiomers of 2,3-pentadieneDo problem 5-14 in the text.Do problem 5-14 in the text.

Fischer ProjectionsFischer Projections Easiest to use when > 1 chiral centerEasiest to use when > 1 chiral center Sugars almost always drawn as FPSugars almost always drawn as FP The carbon chain is always drawn along the The carbon chain is always drawn along the

vertical line of the Fischer projectionvertical line of the Fischer projection The rules for assignment of R,S configurations are The rules for assignment of R,S configurations are

the same.the same.

= C

horizontal is alwayscoming out at you

CC

=

consider each chiralcenter separately

Do problems 5-15, 5-16, 5-17 and 5-18.Do problems 5-15, 5-16, 5-17 and 5-18.

DiastereomersDiastereomers Must have >1 chiral centerMust have >1 chiral center Stereoisomers which are not enantiomers. Stereoisomers which are not enantiomers.

i.e. stereoisomers that are not mirror i.e. stereoisomers that are not mirror images.images.

Have different physical propertiesHave different physical properties The maximum # of stereoisomers = 2The maximum # of stereoisomers = 2nn

where n is the number of chiral centers. where n is the number of chiral centers. Examples of diastereometric relationships Examples of diastereometric relationships

include cis/trans isomerism in rings and cis/ include cis/trans isomerism in rings and cis/ trans isomerism about double bonds.trans isomerism about double bonds.

Do problem 5-19 and 5-22 in the text.Do problem 5-19 and 5-22 in the text.

(2R, 3S)-3-bromo-2-butanol (2R, 3R)-3-bromo-2-butanol

CH3

CH3CH3

CH3

HO

H

H

Br

H

H

HO

Br

DIASTEREOMERSMIRROR IMAGES AT C3 BUT NOT AT C2

DiastereomersDiastereomers

Meso CompoundsMeso Compounds

has >1 chiral centerhas >1 chiral center chiral centers are mirror imageschiral centers are mirror images

» has mirror plane through center of moleculehas mirror plane through center of molecule contains chiral centers, but compound is contains chiral centers, but compound is

achiralachiral» doesn’t rotate lightdoesn’t rotate light

no enantiomeric pair (mirror images no enantiomeric pair (mirror images superimposable)superimposable)

Resolution of EnantiomersResolution of Enantiomers

The separation of enantiomers is called The separation of enantiomers is called resolution.resolution.

A chiral probe is necessary for the resolution A chiral probe is necessary for the resolution of enantiomers. Such a probe is called a of enantiomers. Such a probe is called a resolving agentresolving agent. .

Enantiomers can be resolved chemically or Enantiomers can be resolved chemically or chromatographically.chromatographically.