e m organic chemistry ch-401 course i t b
TRANSCRIPT
Krishna P. Kaliappan, Department of Chemistry, IIT Bombay
CH E
MII T B
Organic Chemistry CH-401 Course
1
Krishna P. KaliappanDepartment of Chemistry
Indian Institute of Technology-BombayMumbai 400 076 INDIA
http://www.chem.iitb.ac.in/[email protected]
10/16/20
Selectivity
CH (401) slides should not be used for commercial purposes
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan3
Selectivity
Chemoselectivity(Which)
Regioselectivity(Where)
Stereoselectivity(How)
Selectivity
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan4
Chemoselectivity
Preferential selectivity of one functional group over other
Two different functional groups of unequal reactivity
Reaction of one of two identical functional groups
Reaction of a group once, when it may react again
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan5
ChemoselectivitySelective Reduction:
Chemoselective reduction of C=C over C=O:
H2/Pd
O O
Chemoselective reduction of C=O over C=C:O OH
NaBH4, CeCl3
Chemoselective reduction of α,β-unsaturated ketones over allylic alcohols:O O
NaBH4, CeCl3
EtOH, -15 oC
OH O
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 6
ChemoselectivitySelective Reduction:
O
O
OH
O
NaBH4 (0.25 eq)
EtOH, 0 oC
O
HO
1/3 BH3
THF
Chemoselective reduction of alkenes over alkenones:
O O(PPh3)3RhCl
H2, EtOH
Chemoselective reduction of alkenones over alkenes:K-Selectride
THF
orMeCu, DIBAL-H
OO
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 7
ChemoselectivityChemoselective reduction of alkynes over alkenes:
H2/ Pd-CaCO3
Quinoline
H2/ Pd-CaCO3
Quinoline
Chemoselective reduction of COOR over CN:
CO2R
CN
Ca(BH4)2
MeOH
CH2OH
CN
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 8
ChemoselectivityChemoselective reduction of α,β-unsaturated esters in presence of alkenes :
EtOOC Mg, MeOH EtOOC
Chemoselective reduction of C=O over COOR:
C
CO2Me
NaBH4
O
MeOH
CO2Me
HO
OHO
OClemmensenreduction
OHO
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 9
ChemoselectivityChemoselective reduction of amides in presence of esters:
NO
COOMe2/3 BH3.THF
N
COOMe
Chemoselective reduction of carboxylic acids in presence of esters, nitro and cyano groups:
O OHOOC BH3, SMe2
THF
O OHOH2C
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 10
Chemoselectivity
Chemoselective oxidation of allylic alcohols over other alcohols:
HO
OH
MnO2
CHCl3 O
OH
Chemoselective oxidation of secondary alcohols over primary alcohols:
OH
OHAgCO3, Celite
Benzene
O
OH
OH
OHNaOCl, AcOH
H2O, 25 oCOH
O
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 11
ChemoselectivityChemoselective oxidation of lactols over other alcohols:
AgCO3, Celite
Benzene
O
OH
OH O
OH
O
Chemoselective epoxidation of allylic alcohols over unfunctionalized alkenes
t-BuOOH
VO(acac)2
OH OHO
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 12
ChemoselectivityChemoselective epoxidation of α,β-unsaturated ketones over alkenes:
OO
KOH, H2O2
O
Chemoselective epoxidation of alkenes over α,β-unsaturated ketones:
O O
O
m-CPBA
DCM
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 13
Chemoselectivity
Chemoselective acylation of amines over phenols:
Chemoselective alkylation of phenols over carboxylic acids:
NH2
OH
Ac2O (1 eq)
Pyridine
NHAc
OH
COOH
OH
COO
O
Base I
Acid
COOH
O
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 14
Chemoselectivity
Reaction of One of Two Identical Functional Groups:
Monoprotection of a diol:
Monohydrolysis of an ester:
HO OHNaH, BnBr
HO OBn
CO2MeCO2Me (1) NaOH, MeOH (1 eq.)
(2) Acid CO2HCO2Me
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 15
Chemoselectivity
Reaction of A Group Once When It May React Again:
Preparation of half esters:
Partial reduction of dinitro compounds:
OH
COCl2
OCOCl
NO2
NO2
NaSH, MeOH
NH2
NO2
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 16
Regioselectivity
Preferential reactivity of one site over the other site of the same functional group
Addition of HBr to alkenes:
Hydration of alkenes:
PhPh OH
(1) Hg(OAc)2
(2) NaBH4
PhOH BH3.THF
Br
HBr
(PhCOO)2O
HBr
Br
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 17
RegioselectivityHydration of alkynes:
Baeyer- Villiger Oxidation:
Birch Reduction:
CHO (1) BH3.THF
(2) NaOH, H2O2
O(1) HgSO4 H2SO4
O CF3CO3H O
O
OMeOMe
Li, NH3
EtOH
COOHLi, NH3
EtOH
COOH
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 18
RegioselectivityDiels-Alder Reaction:
R O
+
R O R
O
major minor
R
O
+
R
O
RO
major minor
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 19
RegioselectivityDiels-Alder Reaction:
O
O
OH
OAc O
O
OH
OAc
O
O
OH
SPh
OAc
O
O
OH
SPh
OAc
O
O
OH
OAcRa Ni,
H2
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 20
RegioselectivityAromatic electrophilic substitution:
OMe OMe
Ac2O
AlCl3
CH3O
CH3 CH3
HNO2
H2SO4NO2
CH3
NO2
MajorE E
HNO2
H2SO4NO2
E
NO2Major
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 21
RegioselectivityAromatic electrophilic substitution:
RCOCl, AlCl3
O
O
RCOCl, AlCl3SiMe3
O
Epoxide Opening:
OMe
Me Me
HNaOMeMeHOMe
OMeH
Me
H2SO4
MeOH
OHMeMe
MeH
MeO