Organic Stereochemistry Notes PDF

SECTION 8 ORGANIC STEREOCHEMISTRY 1 8.1 TYPES OF ISOMERS Isomers: - molecules having the same molecular formula - Constitutional Isomers (structural isomers) differ in bond connectivity...

SECTION 8 ORGANIC STEREOCHEMISTRY 1 8.1 TYPES OF ISOMERS Isomers: - molecules having the same molecular formula - Constitutional Isomers (structural isomers) differ in bond connectivity O OH - Stereoisomers Isomers same bond connectivity but differ in the fixed arrangement of the atoms in 3D space Br H H Br OH OH - Conformational Isomers same bond connectivity but differ in the 3D shape by rotating single bonds (coming in section 9) H H H H H H H H 2 H H H H  Isomers Same number and type of atoms Constitutional Isomers Stereoisomers Conformational Isomers Different in connectivity of Different in spatial orientation Different because of rotations atoms around single bonds H H H H O H H H OH H H H H H Enantiomers Diastereomers Non superimposable mirror images Non superimposable, non mirror images 3 On the previous slide, you can see that one form of 1,3-dimethylcyclopentane (A) is not identical to another (B). Their RELATIVE STEREOCHEMISTRY IS DIFFERENT, so we must distinguish them by their names. A is called cis-1,3-dimethylcyclopentane B is called trans-1,3-dimethylcyclopentane 4 What about the trans molecule C, is it identical to B ? ANSWER: NO ! It’s the NON-IDENTICAL MIRROR IMAGE ENANTIOMERS = Non-identical mirror image molecules A and B are stereoisomers, but they are not enantiomers, they are called DIASTEREOMERS. We will now deal with enantiomers in detail and learn how to distinguish between them by name. 5 Stereoisomers related by being non-superimposable, mirror images of each other (ENANTIOMERS) can be thought of as being left-handed or right-handed. Objects, including molecules, that are not identical with their mirror image are called CHIRAL objects (molecules). 6 8.2 CHIRAL MOLECULES Up to this point you would likely have thought of 2-bromobutane as one molecule, especially when you draw it without 3D information: Br But in 3D reality, it can be either of these two different molecules… Br Br 7 These two possibilities are non-identical mirror images of each other: Br H H Br A B Molecule B turned 180o around the vertical axis clearly shows the two compounds are not the same: Br Br H H A B 8 CHIRAL compounds are not superimposable on their mirror images. ACHIRAL compounds are superimposable on their mirror images. For example: 9 The chiral examples contain an atom that is connected to 4 different groups. This atom is called an asymmetric atom, stereocenter, or stereogenic carbon. We denote asymmetric atoms with an asterisk *. Molecules having one stereocenter are always chiral. Molecules with a plane of symmetry are always achiral. 10 Some practice… Identify if the following molecules are chiral or achiral. If chiral, indicate the stereocenter with an asterisk* * * * achiral chiral achiral achiral chiral How are the following molecules related? identical constitutional stereoisomers isomers (enantiomers) 8.3 OPTICAL ACTIVITY Enantiomers: - cannot be distinguished by their physical properties (boiling points, melting points, and densities). - can be distinguished by the way they interact with plane-polarized light. - are often called optical isomers that possess optical activity Figure 8.2.1 : Operating principle of an optical polarimeter. 1. Light source 2. Unpolarized light 3. Linear polarizer 4. Linearly polarized light 5. Sample tube 6. Optical rotation 7. Rotatable linear analyzer 8. Detector. (CC BY-SA 3.0 Unported; Kaidor via Wikipedia) Clockwise rotation: enantiomer is dextrorotary (+) Counterclockwise rotation: enantiomer is levorotary (-) 12 8.4 ABSOLUTE CONFIGURATION ABSOLUTE CONFIGURATION: - the actual spatial arrangement of the substituent groups around the chiral centers. - each chiral center has one of two possible arrangements (configurations) of its four different groups, and they are mirror images of each other - we denote one configuration around the chiral center as being “R” and its enantiomer (or mirror image) as being “S” - there is no straightforward correlation between the absolute configuration of an enantiomer and the sign of rotation of the molecule. For Example: Dextrorotatory or levorotatory (+ or – ) are determined by experiment Are independent of whether we’ve labelled the chiral center R or S 13 R/S SEQUENCE RULES FOR STEREOCENTERS RULE 1: Look at the atoms attached to the stereocenter. Determine which attached atom has a higher priority based on its atomic number (Z). If you are comparing isotopes, the higher atomic mass has the higher priority. For example: (4) Z1 H C CH3 Z 6 (3) (2) Z 17 Cl Br Z 35 (1) 14  RULE 2: Place the lowest (4th) priority group away from us. For our previous molecule, this gives us the following view: (1) (1) Br Br Cl CH3 CH3 Cl (2) (3) (3) (2) S R A counterclockwise orientation of (1)→(2)→(3) is labelled as the “S” stereochemistry, or “S” absolute configuration A clockwise orientation of (1)→(2)→(3), for the enantiomer, is labelled as the “R” stereochemistry, or “R” absolute configuration 15 RULE 3: What if two substituents have the same atomic number when we consider the atoms directly attached to the stereocenter? Continue along the two substituent chains, atom by atom, until you reach the first point of difference. (1) (2) Br (3) H R RULE 4: Double and triple bonds are treated as if they were single, and we count the double bond atoms twice and triple bond atoms three times. (2) (1) N H2N R (3) 16 8.5 THE STEREOCHEMISTRY OF ALKENES: E and Z ISOMERS Many alkenes can have diastereomers of each other. - stereoisomers that are not mirror images - therefore not enantiomers Example: C4H8 alkenes (1) (2) (3) (4) (1) and (2) are structural isomers of all the others BUT, how do we distinguish the 2-butenes, (3) and (4)? We use the same Priority Rules (named Cahn-Ingold-Prelog Rules) and identify the highest priority group at each end of the double bond. 17 Look at molecule (3): CH3 H C C H CH3 (3) On the left hand carbon of the double bond: -the CH3 group has a higher priority than the H On the right hand carbon of the double bond also: -the CH3 group has a higher priority than the H When the higher priority groups are on opposite sides of the double bond: The name of the molecule is: (E)-2-butene 18 Look at molecule (4): H3C CH3 H H On the left hand carbon of the double bond: -the CH3 group has a higher priority than the H On the right hand carbon of the double bond also: -the CH3 group has a higher priority than the H When the higher priority groups are on the same side of the double bond: The name of the molecule is: (Z)-2-butene 19 More examples: Name the following alkene. Note: alkenes are named as “ene”s giving the double bond the lowest number 5(R)-bromo-3-fluoro-2(Z)-heptene Br F E or Z? O (E) H2N 20 Some practice… Identify the R/S configuration for each chiral center: R S S R S both R Draw the following molecules and rename if not correct: 3S-chloro-2S-ethylpentane 1-methyl-1-bromo-1Z-propene 3S-chloro-4S-methylhexane 2-bromo-2Z-butene  SUGGESTED SECTION 8 EXERCISES FROM LIBRETEXT There are a number of Practice Exercises within each subsection that can provide you with good practice in applying what you have learned. Section 8.1 Types of Isomers Exercises 8.1.1 to 8.1.3 a,b (R/S descriptors are covered in 8.4) Section 8.2 Chiral Molecules Exercises 8.2.1 to 8.2.3, 8.2.5, 8.2.7, 8.2.10, 8.2.12 Section 8.3 Optical Activity Exercises 8.3.3 and 8.3.4 Section 8.4 Absolute Configuration Exercises 8.4.1 to 8.4.9 Section 8.5 Stereochemistry of Alkenes 8.5.1 Exercises 8.5.1.1 to 8.5.1.4 8.5.2 Exercises 8.5.2.1 to 8.5.2.4 22