E FUNCTIONAL GROUP INTERCONVERSIONS CHAPTER 7 123.312 1 functional group interconversions CHAPTER seven reduction 2 R O H H S H H R O H H Cr O O OH previously we had looked at oxidations now we turn our attention to the opposite, reduction 3 R H R OH R NH 2 R Cl R R 1 /H O R R R Cl Cl Cl R R R 1 O OR 1 OH O R OR 1 O R NH 2 O R N R O C O H 2 N O NH 2 Cl Cl Cl Cl oxidation Reduction now adding hydrogen or removing oxygen (or other heteroatom) 4 need to be able to control chemoselectivity R 1 H O R 1 R 2 O R 1 O O R 2 vs vs 5 Text HO HO OH H N OMe salmefamol lets approach this by example & look at the synthesis of this anti-asthma drug 6 NaBH 4 MeO O OH HO N Ph Ph MeO O O HO N Ph Ph starting material contains many reducible groups sodium borohydride only reacts with the ketone & not the ester 7 hydrogenolysis & reductive amination H 2 , Pd / C, H + , ketone MeO O OH HO HN OMe MeO O OH HO N Ph Ph O OMe hydrogenation reductively cleaves benzyl groups (as seen earlier) but... 8 hydrogenolysis & reductive amination H 2 , Pd / C, H + , ketone MeO O OH HO HN OMe MeO O OH HO N Ph Ph O OMe it also reduces imine formed by condensation of amine & ketone in a process called reductive amination 9
Finishing oxidation by looking at the Baeyer-Villiger reaction and then turning our attention to reduction. Once again we will see the usual suspects with a who is who of hydride sources.
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E
FUNCTIONAL GROUPINTERCONVERSIONS
CHAPTER 7
123.3
12
1
functional group interconversions
CHAPTER sevenreduction
2
R O
H H
S
HH
R O
H H
Cr
O
O
OH
previously we had looked atoxidations now we turn our attention to
the opposite, reduction
3
R H
R OH
R NH2
R Cl
R
R1/H
O
R
RR
Cl Cl
Cl
RR
R1O OR1
OH
O
R
OR1
O
R
NH2
O
R
NR O C O
H2N
O
NH2
ClCl
Cl Cl
oxidation
Reduction
now adding hydrogen or removing oxygen (or other
heteroatom)
4
need to be able to control chemoselectivity
R1 H
O
R1 R2
O
R1 O
O
R2vs vs
5
TextHO
HO
OHHN
OMesalmefamol
lets approach this by example & look at the synthesis of this
anti-asthma drug6
NaBH4 MeO
O OH
HON
Ph Ph
MeO
O O
HON
Ph Ph
starting material contains many reducible groups
sodium borohydride only reacts with the ketone &
not the ester
7
hydrogenolysis & reductive amination
H2, Pd / C, H+, ketone
MeO
O OH
HOHN
OMe
MeO
O OH
HON
Ph Ph
O
OMehydrogenation reductively cleaves benzyl groups (as seen
earlier) but...
8
hydrogenolysis & reductive amination
H2, Pd / C, H+, ketone
MeO
O OH
HOHN
OMe
MeO
O OH
HON
Ph Ph
O
OMeit also reduces imine formed by condensation of amine & ketone in a process called
reductive amination9
MeO
O OH
HOHN
OMe
LiAlH4OH OH
HOHN
OMe
ester reduction
finally lithium aluminium hydride reduces the ester