Stereochemistry 2024—JJ
Stereochemistry
Exam 80%
Essay 20%
- Critical analysis
- Use template
- Your opinion is important
Inhoudsopgave
Lecture 1: Stereochemistry introduction—Static & dynamic .....................................................2
Lecture 2: Optical Rotary Dispersion (ORD) and Circular Dichroism (CD) ..................................9
Lecture 3: Conformation analysis and chiral resolution .......................................................... 15
Lecture 4: Diastereoselectivity, chiral synthons, chiral reagents ............................................. 25
Lecture 5: supramolecular and macromolecular chirality ....................................................... 33
Lecture 6: Asymmetric synthesis—Chiral Auxiliaries and reagents .......................................... 45
Lecture 7: Asymmetric Catalysis—Chiral Catalysts ................................................................ 54
Lecture 8: Catalytic oxidation ................................................................................................ 60
Lecture 9: Asymmetric Catalysis – Catalytic hydrogenation & Oxidation .................................. 69
Lecture 10: Asymmetric catalysis—Organo-catalysis ............................................................. 79
1
,Stereochemistry 2024—JJ
Lecture 1: Stereochemistry introduction—Static &
dynamic
Terminology
Absolute configuration: A designation of the position or order of arrangement of the ligands of a
stereo genic unit about an agreed-upon stereochemical standard.
Chiral No plane of symmetry → Can exist 2 enantiomers
Not superimposable on mirror image
Snail → you can’t flip back, doesn’t overlap
Achiral Not chiral, has a superimposable mirror image
⇨ Has plane of symmetry
⇨ Chair
Chirotropic Atom resides in chiral environment
Anchirotopic Opposite of chirotopic
Anomers Diastereomers of glycosides or related cyclic forms of sugars that
specifically epimers at the anomeric carbon.
Anti. Modern usage to describe the relative configuration of two stereogenic
centers along a chain.
The chain is drawn in zigzag from, and if 2 substituents are on
opposite sides of the plane of the paper, they are designated anti.
See also “syn”, “antiperiplanar” and “anticlinal”.
Molecules with plane of symmertry
A structure with a plane of symmetry is achiral.
↳Is superimposable on its mirror image and cannot exist as two enantiomers
Stereogenic center: C vs. N stereochemistry
2
,Stereochemistry 2024—JJ
Achiral, because interchanges, due to movement of the lone pair of the
nitrogen.
➔ Will go back and forth between both forms.
Absolute configuration → CIP rules
↳Cahn-Ingold-Prelog R&S
(R)Clockwise
(S) Counterclockwise
N-inversion
Inversion barriers slightly higher in
simple amines
Quinine is chiral since it cannot interchange/invert/interconvert
NH3 inversion ~5kcal.mol → activation barrier → higher barrier more difficult to isomerize
3
, Stereochemistry 2024—JJ
Inversion rate 5-25 kcal/mol
Too fast cant find 1 enantiomer so not chiral
Higher → can start to find enantiomer because doesn’t interconvert as fast
Chiral cyclic amines
If the nitrogen atom is contained in a small ring, for example, it prevents from attaining the
120˚bond angle that facilitates inversion → Chiral
Strain, so higher activation energy for inversion→ inversion is slow → enantiomers
may be resolved
o Amine is chiral
Different type of stereocenters
Sulfur contains a lone pair (in contrast to carbonyl), therefore
it is not planar, thus it can be chiral.
Chirality at Phosphorus
NH3 5 kcal/mol
PH3 25 kcal/mol
Higher energy barrier, therefore more difficult to isomerize
JT effect 2s/2p vs 3s/3p
➔ Labeling can also make something chiral
Stereogenic centers at heteroatoms
➢ Oxygen can interconvert very fast, however this is not possible when there is a lot of
strain.
➢ N not chiral sp2 hybridized
4
Stereochemistry
Exam 80%
Essay 20%
- Critical analysis
- Use template
- Your opinion is important
Inhoudsopgave
Lecture 1: Stereochemistry introduction—Static & dynamic .....................................................2
Lecture 2: Optical Rotary Dispersion (ORD) and Circular Dichroism (CD) ..................................9
Lecture 3: Conformation analysis and chiral resolution .......................................................... 15
Lecture 4: Diastereoselectivity, chiral synthons, chiral reagents ............................................. 25
Lecture 5: supramolecular and macromolecular chirality ....................................................... 33
Lecture 6: Asymmetric synthesis—Chiral Auxiliaries and reagents .......................................... 45
Lecture 7: Asymmetric Catalysis—Chiral Catalysts ................................................................ 54
Lecture 8: Catalytic oxidation ................................................................................................ 60
Lecture 9: Asymmetric Catalysis – Catalytic hydrogenation & Oxidation .................................. 69
Lecture 10: Asymmetric catalysis—Organo-catalysis ............................................................. 79
1
,Stereochemistry 2024—JJ
Lecture 1: Stereochemistry introduction—Static &
dynamic
Terminology
Absolute configuration: A designation of the position or order of arrangement of the ligands of a
stereo genic unit about an agreed-upon stereochemical standard.
Chiral No plane of symmetry → Can exist 2 enantiomers
Not superimposable on mirror image
Snail → you can’t flip back, doesn’t overlap
Achiral Not chiral, has a superimposable mirror image
⇨ Has plane of symmetry
⇨ Chair
Chirotropic Atom resides in chiral environment
Anchirotopic Opposite of chirotopic
Anomers Diastereomers of glycosides or related cyclic forms of sugars that
specifically epimers at the anomeric carbon.
Anti. Modern usage to describe the relative configuration of two stereogenic
centers along a chain.
The chain is drawn in zigzag from, and if 2 substituents are on
opposite sides of the plane of the paper, they are designated anti.
See also “syn”, “antiperiplanar” and “anticlinal”.
Molecules with plane of symmertry
A structure with a plane of symmetry is achiral.
↳Is superimposable on its mirror image and cannot exist as two enantiomers
Stereogenic center: C vs. N stereochemistry
2
,Stereochemistry 2024—JJ
Achiral, because interchanges, due to movement of the lone pair of the
nitrogen.
➔ Will go back and forth between both forms.
Absolute configuration → CIP rules
↳Cahn-Ingold-Prelog R&S
(R)Clockwise
(S) Counterclockwise
N-inversion
Inversion barriers slightly higher in
simple amines
Quinine is chiral since it cannot interchange/invert/interconvert
NH3 inversion ~5kcal.mol → activation barrier → higher barrier more difficult to isomerize
3
, Stereochemistry 2024—JJ
Inversion rate 5-25 kcal/mol
Too fast cant find 1 enantiomer so not chiral
Higher → can start to find enantiomer because doesn’t interconvert as fast
Chiral cyclic amines
If the nitrogen atom is contained in a small ring, for example, it prevents from attaining the
120˚bond angle that facilitates inversion → Chiral
Strain, so higher activation energy for inversion→ inversion is slow → enantiomers
may be resolved
o Amine is chiral
Different type of stereocenters
Sulfur contains a lone pair (in contrast to carbonyl), therefore
it is not planar, thus it can be chiral.
Chirality at Phosphorus
NH3 5 kcal/mol
PH3 25 kcal/mol
Higher energy barrier, therefore more difficult to isomerize
JT effect 2s/2p vs 3s/3p
➔ Labeling can also make something chiral
Stereogenic centers at heteroatoms
➢ Oxygen can interconvert very fast, however this is not possible when there is a lot of
strain.
➢ N not chiral sp2 hybridized
4
