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PROTECTING GROUP
+ What is protecting group?
n Protecting groups are groups of atoms that are attached to a
functional group to mask it from competitive undesired
reactions and later be removed from that functional group.
protecting deprotecting
n Considerations:
1. protecting group and both protection / deprotection
sequences must be compatible with all other desired
steps and other functional groups.
2. Cheap & commercially available
3. Easy & efficient introduction
4. Should not create any stereogenic center
Stable throughout reaction, work-up & purification
5. Efficient removal: by-products of the removal should be
easily separated
How the
PG works ?
+
The problem of using PG
n Ether can protect a hydroxyl group as an ether without
worrying about it being affected by reactions
n Amines PG
1. Alkyl
2. Amide
3. Sulfonamide
n Amides
+Type of Hydroxyl PG
1. Silyl ether protecting group
n The alcohol group was protected and converted into silyl
ether group
(CH3)3SiCl
Example 1: Using silyl ether to protect OH group
Formation: Cleavage:
+Type of Hydroxyl PG
3. Cyclic acetals
Formation: Cleavage:
+Hydroxyl PG
5. Ester
+Hydroxyl PG
6. Diol Protecting
n All ROH protecting groups work, but 1,2- or 1,3- can be
protected in unique ways.
+
+ The stability of PG
n When more than one alcohol exist, the primary alcohols
(least sterically hindered) will be first protected, then
secondary alcohols (more sterically hindered) and finally
tertiary alcohols
nOHExample 1:
1$equiv.$DHP THP
OH 1$equiv.$DHP
OTHP OTHP
H $$$$$$$$H+ OH
OH $$$$$$$$H+ OH
PCC PCC
H3O+ H3O+
OH OH
OTHP
OH OTHP
H OH
O O
THP
2$equiv.$DHP
n Example 2: HO OH $$$$$$$$H+ THPO OH
OH OTHP
+
n If the oxidation is targeted at primary alcohol, then the
secondary alcohol also should be protected.
OH 1$equiv.$TMS.Cl OTMS
OH $$$$$$$$NEt3 OH
DHP,$H+
THP
O
pcc HF
OH OTMS
H
H3O+ OTHP OTHP
OH
+
n If the same protecting group presence on both alcohols,
deprotection occur on both group which cannot be selective
OH 2$equiv.$DHP OTHP
OH $$$$$$$$H+ OTHP
H3O+
OH
OH
+ 21
v Basic condition
TMS > TES > TBDMS = TBDPS > TIPS
+Ketone and aldehyde PG
1. Acetal
Formation:
Cleavage:
remove the
protecting group
Formation:
Cleavage:
+Amines PG
trifluoroacetamides
Cleavage: NaOH
+Amines PG
5. Alkyl protecting group
n Formation:
BnBr
Cleavage: