Slide 1

Chirality Chirality - the Handedness of Molecules

Isomerswe concentrate on enantiomers and diastereomers

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

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

Enantiomersnow 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 superposablethey are different moleculesnonsuperposable mirror images are enantiomers

EnantiomersObjects that are not superposable on their mirror images are chiral (from the Greek: cheir, hand)they show handednessThe most common cause of enantiomerism in organic molecules is the presence of a carbon with four different groups bonded to ita carbon with four different groups bonded to it is called a stereocenterEnantiomersIf an object and its mirror image are superposable, they are identical and there is no possibility of enantiomerismsuch an object is achiral (without chirality)An achiral molecule, consider 2-propanolnotice that it has no stereocenter

Enantiomersto 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 originalthe original and its mirror image are the same

EnantiomersTo summarizean 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 itwe call a carbon with four different groups bonded to it a stereocenteran object that is superposable on its mirror image is achiral (without chirality)nonsuperposable mirror images are called enantiomersenantiomers, like gloves, always come in pairsDrawing EnantiomersFollowing 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 Imageson the left is one enantiomer of 2-butanolon the right are two representations for its mirror image (in this case, its enantiomer)

The R,S SystemTo assign an R or S configurationassign 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 youread 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 SystemThe first step in assigning an R or S configuration to a stereocenter is to arrange the groups on the stereocenter in order of prioritypriority is based on atomic numberthe higher the atomic number, the higher the priority

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

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

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

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

The R,S SystemBecause enantiomers are different compounds, each must have a different namehere 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 Systemreturning to our original three-dimensional drawings of the enantiomers of ibuprofen

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

StereocentersA molecule with n stereocenters has a maximum number of 2n stereoisomersa molecule with one stereocenter, 21 = 2 stereoisomers (enantiomers) are possiblefor 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 possibleand so forthFischer Projection FormulasFischer Projection: show configuration of chiral molecules in two-dimensional representationVertical bonds are directed awayHorizontal bonds are directed toward you

Enantiomers & Diastereomers2,3,4-Trihydroxybutanal

two stereocenters; 22 = 4 stereoisomers existTwo Stereocenters2,3,4-trihydroxybutanal

diastereomers: stereoisomers that are not mirror images(a) and (c), for example, are diastereomers

Meso CompoundsMeso compound: an achiral compound possessing two or more stereocenterstartaric acidtwo stereocenters; 2n = 4, but only three stereoisomers exist

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

Stereoisomersexample: mark all stereocenters in each molecule and tell how many stereoisomers are possible for eachsolution:

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

Three Or More Stereocenters

***23 = 8 possible stereoisomers RR

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