Stereochemistry and Isomerization

Question 1

Isomers

Answer 1

• compounds with the same molecular formula that differ with respect to either:
  1. the attachment point of their atoms/groups along a carbon hydrogen framework (constitutional/structural isomers); they can be named differently and their groups are located at different positions
  2. differ in the 3D attachment of their groups at given carbons (stereoisomers)

Question 2

Stereoisomers

Answer 2

• they have the same constitution
• they can be divided into further subcategories:

1. conformational isomers
2. configurational isomers

Question 3

conformational isomers (conformers)

Answer 3

• stereoisomers that have the same configurations but differ in how the groups INTERACT in 3D space
• chair “flips” are conformational isomers
• rotation about single bonds can also result in conformational isomers (experiencing different gauche/anti interactions)

Question 4

Configurational isomers

Answer 4

• stereoisomers that have atoms/groups attached differently in 3D space but are still attached to the same carbon
• they can be chiral or achiral
• enantiomers and diastereomers are both examples of configurational isomers

Question 5

enantiomers

Answer 5

• non superimposable mirror images; are configurational opposites at each asymmetric centers (chiral molecules)

Question 6

diastereomers

Answer 6

• configurational isomers that are NOT enantiomers (ex. chiral diastereomers, cis/trans compounds, E/Z double bonds)
• one or multiple configurations are different, but they are not complete opposites

Question 7

stereocenters

Answer 7

• carbons at which the interchange of 2 groups results in the creation of a stereoisomer
• types include:
• asymmetric centers (chiral carbons) - sp3 carbons bonded to four distinct atoms or groups; also called sterogenic centers and classified by R and S
• sp3 carbons of cyclohexanes - cyclic structures restrict carbon single bond rotation and enable cis/trans stereoisomerism
• sp2 carbons of E/Z alkenes - the alkene C-C double bond restricts rotation allowing for E/Z stereoisomerism; to be an E/Z double bond, each carbon of the alkene must have 2 distinct groups

** ALL asymmetric centers are stereocenters but NOT ALL stereocenters are asymmetric centers

Question 8

CIP use

Answer 8

• asymmetric centers are classified as either R or S depending on the clockwise/counterclockwise relationship of their priority groups; priority is determined using the CIP rule system

Question 9

CIP Rule System

Answer 9

1. higher atomic number gets priority over smaller atomic number
2. if atoms attached to a chiral carbon tie in priority (atomic number), then those atoms become the reference point and you now consider the atomic number of the atoms directly attached to the new reference carbons
3. give doubly and triply bonded atoms single bond equivalences (ex. a C–O double bond means that carbon is bonded to two oxygens or 3 if it is a triple bond)
4. Larger isotopes (more neutrons) get priority over smaller isotopes (ex. D (deuterium) is higher priority than H

Question 10

Absolute configuration

Answer 10

• the clockwise or counterclockwise relationship of priority groups about an asymmetric center
• when solving for an absolute config, you must be viewing the lowest priority group at the back of your vision (in the dashed wedged position); if the lowest priority is NOT drawn on the dashed wedged, then an alternative strategy must be utilized

Question 11

Scenario #1 - lowest priority is in the back

Answer 11

1. assign priority according to CIP rules

2. draw a semicircle from 1 to 2 to 3: clockwise = R config and counterclockwise = S config

Question 12

Scenario #2 - lowest priority is on the solid wedge (use when H is NOT in the plane of the page)

Answer 12

1. assign priority according to the CIP rules
2. draw a semicircle from 1 to 2 to 3
3. switch whatever configuration you’re seeing

Question 13

Scenario #3 - lowest priority in the plane (“stick”)

Answer 13

1. assign priority according to CIP rules
2. interchange priority 4 with whatever priority group is in the back
3. draw a semicircle from 1 to 2 to 3
4. switch whatever configuration you’re “seeing”

Question 14

Chiral molecules

Answer 14

• have a non-superimposable mirror image and we call it an enantiomer
• when flipped over a plane of symmetry the solid wedge becomes a dashed wedge bc your perspective is changing
• chiral molecules are optically active
• they often possess asymmetric centers BUT a molecule can have an asymmetric center and still be ACHIRAL (meso)

Question 15

Optically active

Answer 15

• this refers to the observation that chiral molecules have the ability to rotate plane-polarized light
• enantiomers will rotate plane polarized light in opposite directions but with the same magnitude (therefore they cancel each other out)

Question 16

Achiral molecules

Answer 16

• have a superimposable mirror image aka they do NOT have an enantiomer
• they are optically inactive and cannot rotate plane-polarized light
• they can both possess asymmetric centers (meso) or they can lack asymmetric centers

Question 17

Meso compounds

Answer 17

• achiral molecules that possess asymmetric centers and have the following characteristic:
• • possess a constitutional and stereochemical mirror plane
• • an even number of asymmetric centers (but can contain an odd number of stereocenters)
• • enantiomeric asymmetric centers - the asymmetric centers will have complimentary R and S configurations
• • meso compounds will NOT be RR or SS

Question 18

Calculating the number of possible stereoisomers

Answer 18

• the number of theoretical stereoisomers that exists for a compound is calculated by:

2 ^ (n + E/Z), where n = number of asymmetric centers and E/Z is the number of E/Z double bonds

** subtract 1 from the calculation if a stereoisomer is a meso compound

Question 19

Atropisomers

Answer 19

• stereoisomers that lack asymmetric centers but exhibit stereoisomerism due to hindered rotation
• observed in the following types of compounds:
• • allenes
• • substituted biphenyl compounds
• • helical compounds (cyclooctene)
• • BINAP like compounds

Question 20

allenes

Answer 20

• organic compounds that possess sequential C-C double bonds (aka cumulated)
• can be chiral if they have an even number of double bonds and if the terminal carbons of the allene are both bonded to two distinct groups

Question 21

substituted biphenyls

Answer 21

• compounds that possess two benzene rings connected by a single bond
• steric hinderance to free rotation about the sigma bond is introduced when substituents are located at the ortho positions relative to the sigma bond
• steric barrier to rotation is great enough to allow for isolation of distinct stereoisomers
• can be chiral IF : 1) neither ring has two of the same atoms groups 2) if all substituents are located ortho position relative to sigma bond connecting the rings (1,2 position)

Question 22

racemic mixture

Answer 22

• sample containing equal amounts of enantiomers
• solution of racemic enantiomers is achiral (optically inactive) bc the activity is cancelled out by each enantiomer rotating in opposite directions to the same degree

Question 23

enantiomeric excess

Answer 23

• refers to how much of one enantiomer is present, in excess, of the other enantiomer in a mixture of the two
• optical activity of a solution of unequal amounts depends on which enantiomer is present in excess
• ee of 50% means that 50% is pure R (or S) and that 50% is racemic and therefore the ratio of enantiomers present is 75/25 or 3/1

Question 24

EE equation

Answer 24

EE = observed specific rotation (aka the sample optical activity) / specific rotation of pure enantiomer x 100%