R S Nomenclature.ppt

Cahn Ingold Prelog rules to determine absolute configuration

1. Bedanta Kr Borah
Dept. Of Chemistry
Debraj Roy College

2. Stereochemistry
Stereochemistry refers to the
3-dimensional properties and
reactions of molecules. It has its
own language and terms that need
to be learned in order to fully
communicate and understand the
concepts.

3. Definitions
•Stereoisomers–Compoundswiththesamestructural
formulahavingdifferentgeometricalarrangementof
atom/groupinspace
•Enantiomers–Stereoisomersthataremirrorimages;
onlypropertiesthatdifferaredirection(+or-)of
opticalrotation
•Diastereomers–Stereoisomersthatarenotmirror
images;differentcompounds withdifferent
physicalproperties

4. STEREOGENIC CENTER
(Chiral Center)
Carbon has four different groups attached

5. •Arrangement of atoms or groups in
space around the stereocenter of the
molecule is CONFIGURATION
Cl
C
F
Br
H
Cl
C
F
Br
H
enantiomers
Stereocenter
Stereogenic center
-Interchange of 2 atom / groups
gives a stereoisomer

6. Enantiomers
nonsuperimposible mirror imagesOH
CH
3
HO
2C
H
OH
CO2H
CH
3
H
mirror
plane
(S)(+) lactic acid (R)(-) lactic acid
from muscle tissue from milk
[] = +13.5 [] = -13.5
oo

7. Biological Activity(R)(+) Thalidomide (S)(-) Thalidomide
N
N
O
O
O
O
H
H
a sedative and hypnotic a teratogen
N
N
O
O
O
O
H
H

8. •In the 1960’s thalidomide was given to
pregnant women to reduce the effects of
morning sickness.
•This led to many disabilities in babies
and early deaths in many cases.

9. S limonene (lemons) R limonene (oranges)CH3
HCCH2
CH3 CH3
H CCH2
H3C

10. (R), (S) Nomenclature
•Different molecules (enantiomers) must
have different names.C
C
O
OH
H
3C
NH
2
H
natural alanine
=>
•Usually only one enantiomer will be
biologically active.
•Configuration around the
chiral carbon is specified
with (R) and (S).
Absolute Configuration

11. Cahn-Ingold-Prelog Rules Overview
Assignpriorities1,2,3,&4(lowest
priority)toeachgroup
View molecule with the lowest priority away
from the viewer
CircularArrowisdrawnfromtheatom/group
with1stprioritythroughtheatomwith2nd
prioritytotheatomwith3rdpriority.
If arrow points clockwise -
R(rectus)
If arrow points counter-
clockwise -S (sinister)

12. Assign (R) or (S)
•Working in 3D, rotate molecule so that lowest
priority group is in back.
•Draw an arrow from highest to lowest priority
group.
•Clockwise = (R), Counterclockwise = (S)
=>

13. 1
2
3
4
Use Cahn, Ingold, Prelog priorities
Place the lowest priority group back
(focus down C - 4 bond)
(R)
clockwise
draw arrow from 1-2-3
1
2
3
4
(S)
counterclockwise

14. Absolute Configuration1
2
3
4
Use Cahn, Ingold, Prelog priorities
Place the lowest priority group back
(focus down C - 4 bond)
(R)
clockwise
draw arrow from 1-2-3
1
2
3
4
(S)
counterclockwise

15. Assigning priorities-CASE 1
•Assign a priority number to each atom attached to the
chiral carbon.
•Atom with highest atomic number assigned
the highest priorities #1.
In case of isotopes, high(er)est priority given to
the isotope with high(er)est mass number.
CASE 1 -four differentatomsattached to chiral atom

16. Assign Priority to each
Atom/Group on Asymmetric
Center based on atomic
numberfocus down C-4 bond
4
3
2
1I
Cl
H
F
rotate
I
F
H
Cl

17. Lactic Acid(S) (R)
4
3
2
1
4
3
2
1
OH
CH3
CO2H
H
OH
CH
3
HO
2C
H

18. PRIORITY ASSIGNMENT EXAMPLES
CASE 2 -In case of ties among 1st atom, go to 2nd
atoms, then to 3rd etc until the tie is broken.
Consider straight chain groups
Me < Et<n-propyl etc
Consider effect of branching
Et< isopropyl < tert-butyl
Consider effect of hetero atom
Tert-butyl < CH
2OMe

19. C.I.P. PrioritiesCH
2CH
2CH
3 CH(CH
3)
2
CH
2CH
2OH CH
2CH
O
CH2CH2CH3 CH=CH2
CO
2H CH
2Cl
Low High
CH2CH2Br CH(CH3)2

20. Groups possessing multiple bonds
Carbondoublybondedisequivalenttoacarbon
bondedtotwosinglebond,triplebondedis
equivalenttothreesinglebond.C
H
O CH
O
O C
H
C CH
C
C C CH CH
C
C
C

22. Assign PrioritiesC
C
O
OH
H
3C
NH
2
H
natural alanine
1
2
3
4Cl
HCl
H
*
1
2
3
4
1
2
3
4
=> C
C
O
H
C
H
CH
2
CH2OH
CH(CH3)2
* C
C
C
CH2OH
CH(CH3)2
H
O
O
C
C
H CH2
C
*
expands to

23. A CarbohydrateCHO
CH2OH
H OH
HO H
H OH
H OH
(+) D-Glucose
R
S
R
R

24. Fischer ProjectionsVertical bonds move away (dashed bonds)
Horizontal bonds approach you (wedge bonds)
OH
CO2H
CH
3
H
OH
CH3
HO
2C
H
OH
CO2H
CH3
H

25. Assigning Absolute
Configuration to Fischer
ProjectionsOH
CO2H
CH
3
H
OH
CO2H
CH3
H
OH
CH3
HO2C
H
(S) (S) (S)
rotate

26. Rotation of the Projection 90
o
Reverses Absolute Configuration90
o
90
o
o
90
(S) (R) (S) (R)
CH
3
H
OH
HO
2C
CO2H
CH
3
H
HO
H
OH
CO
2H
CH
3
OH
CO
2H
CH
3
H

27. Diastereomers
Stereoisomers That Are Not Mirror Images3 3
22
opposite stereochemistry at C3
same stereochemistry at C2 (S)
CO
2H
OHH
BrH
CO
2H
OHH
BrH
(2S,3S) (2S,3R)

28. Fischer Projections with 2
Chiral CentersCO2H
CH
3
H OH
Br H H Br
H OH
CO2H
CH
3
(2S,3S) (2S,3R)
2
3
2
3

29. 2 Chiral Centers
4 Stereoisomers

30. Identical, Enantiomers or
Diastereomers?H
H
CH3
CH3
&
CH3
CH
3
H
H
CC
a)
CH2CH3
CH3
H
H
Br
Br
CH2CH3
CH3&
b)
OH
HO
NH2
NH2

31. Tartaric AcidsCO2H
CO2H
H OH
HO H H OH
HO H
CO2H
CO2H
CO2H
CO2H
H OH
H OH HO H
HO H
CO2H
CO2H
R,R S,S
R,S S,R

32. Racemic Mixtureo
(g/mL) 1.7598 1.7598 1.7723
m.p. C 168-170 168-170 210-212
[] (degrees) - 12 + 12 0
(R,R) Tartaric acid (S,S) Tartaric Acid (+/-) Tartaric acid
Racemic Mixture (Racemate): 50/50 mixture of enantiomers
CO2H
CO
2H
H OH
HO H H OH
HO H
CO2H
CO
2H
R,R S,S

33. MesoCompound
Internal Plane of Symmetry
Optically Inactiveo
rotate 180
superimposible
CO
2H
CO2H
H OH
H OH HO H
HO H
CO2H
CO2H
R,S S,R
mirror
plane

34. 2,3,4-trichlorohexane
How many stereoisomers?Cl
Cl
Cl
3 asymmetric centers
8 stereoisomers
* **
2
n, n= # asymmetric centers (3)

35. n = 3; 2
n
= 8CH
3
CH2CH3
H Cl
ClH
H ClCl H
H Cl
ClH
CH
3
CH
2CH
3
CH3
CH
2CH
3
ClH
H Cl
H Cl Cl H
ClH
H Cl
CH3
CH
2CH
3
H Cl
H Cl
H Cl
CH3
CH2CH3
Cl H
ClH
ClH
CH3
CH2CH3
Cl H
H Cl
H Cl
CH3
CH2CH3
H Cl
ClH
ClH
CH3
CH2CH3
S
S
R
R
R
S

36. A CarbohydrateCHO
CH2OH
H OH
HO H
H OH
H OH
(+) D-Glucose
R
S
R
R

37. Internal Planes of SymmetryCH
3CH
3
CH3CH3
CH
3CH
3
CH
3 CH
3
Both are Meso

38. Asymmetric Centers on RingsBr
Br
Br
Br
1(R),2(S) cis 1,2-dibromocyclohexane
nonsuperimposible but A flips into B
A B
BrBr
Meso

39. Allenes can be ChiralCCC
H
CH3
CC
Cl
H
C
CH
3
H
Cl
H

40. Mycomycin, an antibioticCCC
H
CH=CHCH=CHCH2CO2H
CCCCH
H
Nocardia acidophilus[]
D = -130
o

41. Reactions that Generate
Chirality Centers
Hydrogenation, synCH
3CH
3
CH2CH3CH2CH3
H2, Pt/C
CH2CH3 CH2CH3
CH
3CH
3
HH
CH2CH3
CH2CH3
HCH3
HCH3
product is meso

42. Bromination
Transis formed exclusively
No Meso is formed (cis)racemic mixture
S SR R
BrBrBrBr
Br2

43. Bromonium Ion is Opened
Equally from Both SidesBr
2
BrBr BrBr
R R S S
racemic mixture
Br
Br
Br
Br
BrBr

+-

44. transalkene + anti addition = MESOCH2CH3
CH
2CH
3 H
H
Br
2
CH2CH3
CH2CH3
H
H
Br
Br
Br Br
CH2CH3CH2CH3
HH
meso

45. cisAlkene + anti addition =
racemic mixtureH
CH
2CH
3 CH
2CH
3
H
Br2
Br Br
CH2CH3
CH2CH3 H
H
R R
CH
2CH
3
CH2CH3
H
H
Br
Br
CH2CH3
CH2CH3 H
H
Br Br
S S
Br
H H
CH2CH3CH2CH3
Br
Br
Br
H
H
CH2CH3
CH
2CH
3
a b
a b

46. Brominations Often Generate
Asymmetric CentersBr2
R RS S
racemic mixture
CH3CH3
H H
CH3CH3
Br Br
H H
CH
3CH
3
BrBr
H
H
CH3
CH3 H
H CH3
CH3
H
H
Br
Br
CH3CH3
BrBr
H
H
S R
meso
Br2

47. Asymmetric Center is Generated
Racemic Mixture FormedH-Br
H
H
Br
Br
a)
b)
Br
H
a)
Br
H
b)(R) (S)

48. Asymmetric InductionPPh2
PPh2
RuCl2
CH3
OH
H2
Ru(BINAP)Cl
2
CH3H
OH
96% e.e.
Noyori and Knowles shared Nobel Prize in Chemistry, 2001

49. Preparation of (L)-Dopa
for Treatment of Parkinson’sHO
HO
CH2C
CO2H
NH2
H
l-(-) Dopa
HO
HO
CH
2CH
2NH
2
Dopamine
cannot cross blood-brain
barrier
C=C
NH2
CO2HH
HO
HO
H2
Rh(DIOP)Cl2
enz.

50. Relevance of Stereochemistry(S,S)(R,S)
useful decongenstants
d-pseudoephedrine and l-ephedrine
4 stereoisomers
**
2 asymmetric centers
EPHEDRA from Ma Huong
NHCH3
CH
3
OH

51. One-step synthesisPseudophed
*
d-(S)- "Meth"
l-(R) - Vicks
(methamphetamine)
"desoxyephedrine"NHCH3
CH
3

52. -(p-isobutylphenyl)propionic acidCH3
CO2H
H
(S)(+) ibuprofen (R)(-) ibuprofen
CH
3
HO
2C
H
anti-inflammatory 80-90% metabolized to (S)(+)

53. Model of Thalidomide

54. How Sweet it is!Sucrose
O
HO
OH
O
CH
2OH
O
CH
2OH
CH2OH
HO
HO
OH
Sucralose or Splenda
O
Cl
HO
OH
O
CH
2OH
O
CH
2Cl
CH
2Cl
HO
HO
Sucraloseis 600 times sweeter
and does not get metabolized.

55. Sildenafil (Viagra) and
CaffeineN
N
N
N
CH3
H
O
CH3CH2O
S
N
N
CH3
O
O
N
N
N
N
CH
3
O
O
CH3
CH3

56. Radiosensitizer of Choice Until
2004Okadaic acid
17 asymmetric centers
O
OH
HOOC
OH
O
H
O
O
H
H
O
OH
H
OH
O
O