Chem 201/Beauchamp Topic 7, Stereochemistry 1 Isomer Overview The following table summarizes the various types of isomers we will encounter as we proceed through organic chemistry. Isomers - compounds that have the same formula Constitutional or structural Stereoisomers have their atoms isomers have their atoms attached with the same connectivity, joined together in different but differ in their arrangements in arrangements space chain or skeletal positional functional isomers isomers group isomers Cl O OH butane 1-chloropropane Cl H propanal prop-2-en-1-ol (aldehyde) (allyl alcohol) O O 2-methylpropane 2-chloropropane oxatane propanone (cyclic ether) (ketone) Conformational isomers Enantiomers are mirror Diastereomers are differ by rotation about a image reflections that stereoisomers that single bond and are usually are not superimposable are not mirror images easily interconverted. (different). of one another. CH a. 3 CH3 CH3 OH OH fast H C OH H C OH HO C H fast C C vs. CH3CH2 H2CH3C H H H C OH H C OH HO C H H3C CH3 CH 3 CH3 CH3 CH3 CH H H 3 meso (dl) enantiomers b. fast H CH3 CH3 H E or trans Z or cis (dl) or () enantiomer pairs also called H CH H H 3 geometric isomers and cis/trans isomers CH3 CH3 CH3 H cis trans Chem 201/Beauchamp Topic 7, Stereochemistry 2 Essential Vocabulary of Stereochemistry – terms to know for this topic Chiral center – a tetrahedral atom with four different groups attached, a single chiral center is not superimposable on its mirror image, also called a stereogenic center, and asymmetric center Stereogenic center – any center where interchange of two groups produces stereoisomers (different structures), could be a chiral center producing R/S differences, or an alkene producing E/Z differences or cis/trans in a ring Absolute configuration (R and S) – the specific 3 dimensional configuration about a tetrahedral shape, determined by assigning priorities (1-4) based on the highest atomic number of an atom at the first point of difference. When the lowest priority group is away, a circle is traced through the highest 3 priorities (1 2 3) in a clockwise direction (= R) or a counterclockwise direction (=S) E/Z Nomenclature – a system to unambiguously identify the stereochemistry at alkenes based on the priorities of the attached groups at each carbon. E has the highest two priority groups on the opposite side of the double bond and Z has the highest two priority groups on the same side of the double bond. Chiral Molecules – a molecule that is not superimposable upon its mirror image Achiral Molecules – a molecule that is superimposable upon its mirror image Enantiomers – stereoisomers that are different mirror images of one another, there can only be one enantiomer Diastereomers – stereoisomers that are not mirror images of each other, can be a result of either (R/S) differences, (E/Z) differences in alkenes, cis/trans differences in rings or any combination of all those kinds of differences; there may be many, many diastereomers. Meso Compounds – compounds that contain two or more chiral centers, yet are identical with their mirror images (they are achiral and optically inactive). A mirror plane cuts through the middle of the molecule. Optical Activity – angle of rotation of plane polarized light using a polarimeter as it passes through a solution of chiral compound, achiral compounds do not rotate plane polarized light and are optically inactive (no rotation). d (+) = dextrorotatory – clockwise rotation of plane polarized light in a polarimeter (only with chiral compounds) l (-) = levorotatory – counterclockwise rotation of plane polarized light in a polarimeter (only with chiral compounds) Racemic Mixture – a equal mixture of two enantiomers. Racemic mixtures are optically inactive even though there are chiral molecules present. Each enantiomer cancels out the optical rotation of the other enantiomer. Fischer Projections – a method for representing stereogenic centers in chains, with the stereogenic carbon at the intersection of vertical and horizontal lines, the horizontal lines are consider to be coming forward in front of the plane (wedges) and the vertical lines are considered to be going backward behind the plane (dashes). Haworth Projections – a method for representing cyclic structures, drawn flat with vertical lines to show top and bottom faces of the ring, analogous to Fischer projections for straight chains. Commonly used for cyclic sugars in biochemistry. Prochiral – molecules are those that can be converted from achiral to chiral in a single step (re and si faces). Enantiomeric excess (ee) is a measure for how much more of one enantiomer is present compared to the other (50% ee in R is 75% R and 25% S) Other types of chirality include axial (helical) chirality (allenes, DNA) and planar chirality (E-cyclooctene). Chem 201/Beauchamp Topic 7, Stereochemistry 3 How many butan-2-ols are there? At first, it seems there must be only one. But let’s build models and compare. mirror plane OH OH OH H 2 C C H3C C C CH3 H H CH3 H C CH 3 H C 2 H2C H 3 CH3 S absolute configuration R absolute configuration 2D representation of butan-2-ol 3D representation of butan-2-ol reveals two different mirror images (called enantiomers) Three dimensional structures of 2-butan-2-ol reveal that there are two different butan-2-ols which are mirror images of one another. Different mirror images are called enantiomers. This property can be observed in enantiomeric molecules using plane polarized light. Rotation of plane polarized light can rotate either to the right (dextrorotatory = d = +) or to the left (levorotatory = l = -) depending on the substance. Such samples are called ‘optically active’ and have a similar relationship to one another as your left and right hands. The property of handedness will be observed at any tetrahedral center with four different groups present. chiral center 1 1 chiral center (stereogenic) (stereogenic) These are different mirror images and called enantiomers. C C 4 4 # # = priorioty of groups attached to chiral center, 2 2 (1 > 2 > 3 > 4), discussed later in text. 3 3 Determines absolute configuration as R (R)-absolute configuration mirror (S)-absolute configuration (rectus / right) and S (sinister / left). plane Any tetrahedral carbon with four different groups about it is called a chiral center and a stereogenic center. In an actual molecule, there may be only one chiral center or 10s, 100s, 1000s or more chiral centers. 1 1 rotate 180o along center NOT mirror images. 4 C axis C 3 2 2 3 4 If a 50/50 racemic mixture of different mirror image structures (enantiomers) is present, this will lead to no observed rotation of polarized light because the right and left rotations cancel. 1 1 A racemic mixture occurs when both mirror images are present in equal amounts. Each rotation cancels 4 C C 4 the other for no net observed rotation. 2 2 3 3 mirror plane Racemic mixture = 50/50 mixture of enantiomers Chem 201/Beauchamp Topic 7, Stereochemistry 4 If there are no chiral centers then the mirror image structures are really identical, and this leads to no net observed rotation of polarized light (any right rotation is cancelled by an equal amount of left rotation). 1 1 Both mirror images are identical (achiral) - no net 3 C C 3 rotation of light. 2 3 2 3 Molecular models you always carry with you – They’re called hands! This subtle difference in structure can be very difficult to visualize on paper or even with models. However, it turns out that nature gave us the perfect tools to consider this difficult 3D problem. Those tools are called hands (and of course, we have our minds)! Our hands can reveal some of the problems we face in working with enantiomers, and some of the solutions to those problems. Many of us will have a problem picturing abstract molecules in space, especially different mirror image molecules. Almost none of us will have a problem picturing mirror image hands, because of our lifetime experience using them. Let’s draw the outline of a hand. If we don’t use more specific nomenclature, we wouldn’t know if the hand is a right hand or a left hand? Either of your hands would fit in the first trace of a hand below. What further information do we need? We could say “right” or “left”, or we could add some additional details to our drawings. A plain silhouette does not provide enough information to tell if the hand is Added features make face up or face down it easy to determine if (left or right). the top or the bottom of the hand is towards you (...or you could add a descriptor of left hand = ? right hand left hand or right). Our mental image of enantiomers (different mirror images) is rock solid when we’re talking about hands. We don’t really even need a picture to distinguish right from left. From a lifetime experience of using them, we know that our two hands, while looking similar, are very different from one another. Just try switching hands the next time you are taking notes in organic chemistry. Almost every detail we need to understand about molecules can be modeled with your hands. You can even use your hands as approximations of tetrahedral atoms, using your arm, thumb and first two fingers. Try it using the pictures below as an example. Use your hands to model tetrahedral centers and this subject will be a whole lot easier. Chem 201/Beauchamp Topic 7, Stereochemistry 5 right hand ...or... left hand arm arm middle middle finger thumb thumb finger pointer mirror pointer finger images finger R and S Nomenclature (Absolute configuration as R or S) In addition to recognizing when enantiomers are present (stereoisomers in general), we also have to correct our nomenclature so that it is specific enough to identify a unique structure.