Chapter 15 Principles of Stereochemistry Chapter 15 Principles of Stereochemistry ***Bring Your Model Kits to Class!***

Stereoisomers: compounds that have the same connectivity, but a different arrangement of atoms in space Enantiomers: molecules that are non-superimposable (non-congruent) mirror images

Enantiomers

Carvone

Problem Draw the missing enantiomer:

Enantiomers are said to be “chiral” They possess the property of “chirality” Greek: “hand” or “handedness” No plane of symmetry

If a molecule is superimposable on its mirror image it is said to be “achiral” Has a plane of symmetry

Chiral Carbons Many chiral molecules contain one or more asymmetric carbons Called “Chiral Carbons” Attached to four different groups Denoted by an asterisk Source of stereoisomerism Interchange of groups = other stereoisomer Stereocenters

Problems Identify, with an asterisk, the chiral carbons in the following molecules:

How do we differentiate between these two enantiomers How do we differentiate between these two enantiomers? What do we call them?

Nomenclature of Enantiomers Identify your chiral carbon Prioritize your substituents on the chiral carbon according to the Cahn-Ingold-Prelog priority rules Highest priority = 1, Lowest Priority = 4 Priority assignment rules: Higher atomic # = higher priority Higher isotopic mass = higher priority

If the first atoms connected to the chiral carbon are the same, continue moving outward until the first point of difference

Multiple-bonded atoms are equivalent to the same number of single bonded atoms

Point the lowest priority substituent away from you and look at the 3 remaining groups in a plane Count  1, 2, 3 If you go CW = R (rectus, Latin “proper”) If you go CCW = S (sinister, Latin “left”)

Name your enantiomers by placing an “(R)-” or an “(S)-” in front of the molecule’s IUPAC name

Problems Identify whether the following molecules are R or S. Identify and name the following molecules:

For pharmaceuticals, slight differences in 3D spatial arrangement can make the difference between targeted treatment and undesired side effects. WHY?

Physical Properties of Enantiomers Enantiomers share identical physical properties m.p., b.p., nD, density, heats of formation etc. Example: Lactic Acid m.p. = 53°C b.p. = 122°C Lactic Acid

Enantiomers rotate a plane of polarized light in equal, but opposite directions Called “Optical Activity” Use Polarimeter

Optical Activity If the sample rotates the plane of polarized light CW → dextrorotatory (+) Latin: Dexter = Right If the sample rotates the plane of polarized light CCW → levorotatory (-) Latin = Laevus = Left If one enantiomer is +, the other will be – (+)-lactic acid (–)-lactic acid

The sign of optical rotation is unrelated to R and S configuration of a compound (S)-(+)-lactic acid (R)-(–)-lactic acid

Optical rotation (a) is a quantitative measure of optical activity [a] = a/cl [a] = specific rotation a = Observed rotation (degrees) c = concentration (g/mL) l = path length (dm) Often, temp and wavelength indicated

(S)-(-)-glyceraldehyde [α]20 = -13.5° mL g-1 dm-1 (R)-(+)-glyceraldehyde [α]20 = +13.5° mL g-1 dm-1

Racemic Mixtures Racemic mixture/Racemate: a mixture containing equal amounts of two enantiomers typically have different physical properties from that of the pure enantiomers Example: Lactic Acid m.p. (R or S) = 53°C m.p. (R and S)= 17°C Indicating racemic mixture: Racemic Lactic Acid (±)-Lactic Acid Optical rotation = 0

Celexa vs. Lexapro Celexa = racemic mixture Lexapro = enantiopure S R-(−)-citalopram S-(+)-citalopram Celexa = racemic mixture Lexapro = enantiopure S escitalopram

Fischer Projections Convenient 2D representation of 3D carbohydrate molecules Carbon chain written vertically All bonds depicted horizontally and vertically Chiral carbons are represented by crossing lines

Vertical bonds go back Horizontal bonds come forward

Fischer Projections – More Complex Based on an eclipsed molecular conformation

An interchange of any two of the groups bound to an asymmetric carbon changes the configuration of that carbon

Problems Draw the enantiomer for the following molecule. Then, draw it as a molecular representation with dashes and wedges. Which is R? Which is S? How many chirality centers does the following molecule possess? Draw L-Glucose.

Isomer Identification Flowchart

Molecules with more than one chirality center have mirror image stereoisomers that are enantiomers In addition they can have stereoisomeric forms that are not mirror images, called diastereomers

Diastereomers and Enantiomers

Fischer Projections can also be used to quickly assess stereoisomeric relationships

Problem Which of the following molecules are enantiomers? Which are diastereomers?