Chirality Chirality - the Handedness of Molecules

Isomers we concentrate on enantiomers and diastereomers

Enantiomers Enantiomers: nonsuperposable mirror images as an example of a molecule that exists as a pair of enantiomers, consider 2-butanol

Enantiomers one way to see that the mirror image of 2-butanol is not superposable on the original is to rotate the mirror image

Enantiomers now try to fit one molecule on top of the other so that all groups and bonds match exactly the original and mirror image are not superposable they are different molecules nonsuperposable mirror images are enantiomers

Enantiomers Objects that are not superposable on their mirror images are chiral (from the Greek: cheir, hand) they show handedness The most common cause of enantiomerism in organic molecules is the presence of a carbon with four different groups bonded to it a carbon with four different groups bonded to it is called a stereocenter

Enantiomers If an object and its mirror image are superposable, they are identical and there is no possibility of enantiomerism such an object is achiral (without chirality) An achiral molecule, consider 2-propanol notice that it has no stereocenter

Enantiomers to see the relationship between the original and its mirror image, rotate the mirror image by 120° after this rotation, we see that all atoms and bonds of the mirror image fit exactly on the original the original and its mirror image are the same

Enantiomers To summarize an object that is nonsuperposable on its mirror image is chiral (it shows handedness) the most common cause of chirality among organic molecules is the presence of a carbon with four different groups bonded to it we call a carbon with four different groups bonded to it a stereocenter an object that is superposable on its mirror image is achiral (without chirality) nonsuperposable mirror images are called enantiomers enantiomers, like gloves, always come in pairs

Drawing Enantiomers Following are four different representations for one of the enantiomers of 2-butanol both (1) and (2) show all four groups bonded to the stereocenter and show the tetrahedral geometry (3) is a more abbreviated line-angle formula; although we show the H here, we do not normally show them in line-angle formulas (4) is the most abbreviated representation; you must remember that there is an H present on the stereocenter

Drawing Mirror Images on the left is one enantiomer of 2-butanol on the right are two representations for its mirror image (in this case, its enantiomer)

The R,S System To assign an R or S configuration assign a priority from 1 (highest) to 4 (lowest) to each group on the stereocenter; orient the stereocenter so that the group of lowest priority is facing away from you read the three groups projecting toward you in order from (1) to (3) if reading the groups is clockwise, the configuration is R (Latin, rectus, straight, correct) if reading the groups is counterclockwise, the configuration is S (Latin: sinister, left)

The R,S System The first step in assigning an R or S configuration to a stereocenter is to arrange the groups on the stereocenter in order of priority priority is based on atomic number the higher the atomic number, the higher the priority

The R,S System Example: assign priorities to the groups in each set

The R,S System Example: assign priorities to the groups in each set

The R,S System example: assign an R or S configuration to each stereocenter

The R,S System example: assign an R or S configuration to each stereocenter

The R,S System Because enantiomers are different compounds, each must have a different name here are the enantiomers of the over-the-counter drug ibuprofen the R,S system is a way to distinguish between enantiomers without having to draw them and point to one or the other

The R,S System returning to our original three-dimensional drawings of the enantiomers of ibuprofen

Chirality in Biomolecules a molecule and its enantiomer or one of its diastereomers elicit different physiological responses as we have seen, (S)-ibuprofen is active as a pain and fever reliever, while its R enantiomer is inactive the S enantiomer of naproxen is the active pain reliever, but its R enantiomer is a liver toxin!

Stereocenters A molecule with n stereocenters has a maximum number of 2n stereoisomers a molecule with one stereocenter, 21 = 2 stereoisomers (enantiomers) are possible for a molecule with two stereocenters, a maximum of 22 = 4 stereoisomers (two pair of enantiomers) for a molecule with three stereocenters, a maximum of 23 = 8 stereoisomers (four pairs of enantiomers) is possible and so forth

Fischer Projection Formulas Fischer Projection: show configuration of chiral molecules in two-dimensional representation Vertical bonds are directed away Horizontal bonds are directed toward you

Enantiomers & Diastereomers 2,3,4-Trihydroxybutanal two stereocenters; 22 = 4 stereoisomers exist

Two Stereocenters 2,3,4-trihydroxybutanal diastereomers: stereoisomers that are not mirror images (a) and (c), for example, are diastereomers

Meso Compounds Meso compound: an achiral compound possessing two or more stereocenters tartaric acid two stereocenters; 2n = 4, but only three stereoisomers exist

Stereoisomers example: mark all stereocenters in each molecule and tell how many stereoisomers are possible for each

Stereoisomers example: mark all stereocenters in each molecule and tell how many stereoisomers are possible for each solution:

Three Or More Stereocenters how many stereocenters are present in the molecule on the left? how many stereoisomers are possible? one of the possible stereoisomers is menthol assign an R or S configuration to each stereocenter in menthol

Three Or More Stereocenters * R * * 23 = 8 possible stereoisomers

Stereoisomers The 2n rule applies equally well to molecules with three or more stereocenters