Selectivity

Selectivity

Chemoselectivity Regioselectivity Stereoselectivity

(Which) (Where) (How)

1  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity

Preferential selectivity of one functional group over other

Two different functional groups and unequal reactivity

Reaction of one of two identical functional groups

Reaction of a group once, when it may react again

2  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Selective Reduction:
Chemoselective reduction of C=C over C=O:
O O
H2/Pd

Chemoselective reduction of C=O over C=C:

O OH
NaBH4, CeCl3

Chemoselective reduction of α,β-unsaturated ketones over

allylic alcohols:
O O OH O
NaBH4, CeCl3

EtOH, -15 oC

3  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Selective Reduction:
OH O O
NaBH4 (0.25 eq) 1/ BH3
3

O O HO

Chemoselective reduction of alkenes over alkenones:

O (PPh3)3RhCl O

H2, EtOH

Chemoselective reduction of alkenones over alkenes:

K-Selectride
O O
THF

or
MeCu, DIBAL-H

4  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Chemoselective reduction of alkynes over alkenes:
H2/ Pd-CaCO3

Quinoline

H2/ Pd-CaCO3

Quinoline

Chemoselective reduction of COOR over CN:

CO2R CH2OH
Ca(BH4)2

CN MeOH CN

5  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Chemoselective reduction of α,β-unsaturated esters in
presence of alkenes :

Mg, MeOH
EtOOC EtOOC

Chemoselective reduction of C=O over COOR:

O HO
C

NaBH4

MeOH
CO2Me CO2Me
O
Clemmensen
reduction

HO HO
O O
6  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Chemoselective reduction of carboxylic acids in presence
of esters, nitro and cyano groups:

O BH3, SMe2 O
HOOC O HOH2C O
THF

Chemoselective reduction of amides in presence of esters:

COOMe COOMe
2/
3 BH3.THF

O N N

7  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Selective Oxidation:
Chemoselective oxidation of allylic alcohols over other alcohols:
OH OH

MnO2

HO CHCl3 O

Chemoselective oxidation of secondary alcohols over primary

alcohols:
OH O
AgCO3, Celite
OH OH
Benzene

OH NaOCl, AcOH O

OH OH
H2O, 25 oC

8  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Selective Oxidation:
Chemoselective oxidation of lactols over other alcohols:

O OH O O
AgCO3, Celite

Benzene
OH OH

Chemoselective epoxidation of allylic alcohols over

unfunctionalized alkenes:
t-BuOOH
O
OH VO(acac)2 OH

9  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Chemoselective epoxidation of α,β-unsaturated ketones over
alkenes:
O
O O
KOH, H2O2

Chemoselective epoxidation of alkenes over α,β-unsaturated

ketones:

O m-CPBA O

DCM

10  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Chemoselective acylation of amines over phenols:
NH2 NHAc
Ac2O (1 eq)

Pyridine
OH OH

Chemoselective alkylation of phenols over carboxylic acids:

COOH
COOH COO
I
Base

Acid O
OH O

11  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Reaction of One of Two Identical Functional Groups:
Monoprotection of a diol:
NaH, BnBr
HO OH HO OBn

Monohydrolysis of an ester:

(1) NaOH, MeOH (1 eq.) CO2Me

CO2Me
CO2Me (2) Acid CO2H

12  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Chemoselectivity
Reaction of A Group Once When It May React Again:
Preparation of half esters:
OH OCOCl

COCl2

Partial reduction of dinitro compounds:

NO2 NH2

NaSH, MeOH

NO2 NO2

13  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Regioselectivity
Preferential reactivity of one site over the other site of the
same functional group

Addition of HBr to alkenes:

Br
Br

HBr HBr

(PhCOO)2O

Hydration of alkenes:
Ph Ph Ph OH
OH BH3.THF (1) Hg(OAc)2

(2) NaBH4

14  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Regioselectivity
Hydration of alkynes:
O
(1) HgSO4
(1) BH3.THF H2SO4
CHO
(2) NaOH, H2O2

Baeyer- Villiger Oxidation:

O CF3CO3H O

O
Birch Reduction:
OMe OMe COOH COOH
Li, NH3 Li, NH3

EtOH EtOH

15  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Regioselectivity
Diels-Alder Reaction:
R R O R
O

+ O

major minor

O
R R
R
+

O
O major minor

16  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Regioselectivity
Diels-Alder Reaction:
O O

O O OAc O O OAc
H H

O OAc O OAc O OAc

Ra Ni,
H2

O O SPh O O SPh O O
H H H

Epoxide Opening:
HO Me O H2SO4 Me OH
NaOMe Me H
Me H Me H
Me Me MeOH MeO Me
Me OMe

17  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Selectivity
Regioselectivity
Aromatic electrophilic substitution:

HNO2

H2SO4 NO2
NO2

Friedel-Crafts Reaction:
O

RCOCl, AlCl3

O
O
SiMe3 RCOCl, AlCl3

18  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan