protecting groups for organic synthesis · 2018-08-30 · 2 protecting groups for organic synthesis...
TRANSCRIPT
1
Protecting Groups for Organic Synthesis
SangheeSanghee KimKim
School of Pharmacy,School of Pharmacy,Seoul National UniversitySeoul National University
Protecting Groups for Organic Synthesis
General References:
– Kocienski, P. J. Protecting Groups, 3rd ed.; GeorgThieme Verlag: New York, 2005.
– Greene, T. W.; Wuts, P. G. M. Protective Groups In Organic Synthesis, 3rd ed.; John Wiley & Sons: New York, 1991.
2
Protecting Groups for Organic Synthesis
Contents:
• Protection of 1. Hydroxyl groups2. Ketones and aldehydes3. Amines4. Carboxylic Acids5. Alkynes
Protecting Groups for Organic Synthesis
Protecting groups ?
– Protect functional groups which may be incompatible with a set of reaction conditions
– 2 step process : introduction & removal must be efficient– Selectivity
• selective protection• selective deprotection
When one protective group is stable to conditions that cleave another and the converse is also true, these groups are often said to be to bear an orthogonal relationship.
3
Hydroxyl Protecting GroupsAcetals
Hydroxyl Protecting GroupsAcetals
4
Hydroxyl Protecting GroupsAcetals
Hydroxyl Protecting GroupsAcetals
5
Hydroxyl Protecting GroupsAcetals
Hydroxyl Protecting GroupsAcetals
6
Hydroxyl Protecting GroupsEthers
Hydroxyl Protecting GroupsEthers
7
Hydroxyl Protecting GroupsEthers
Hydroxyl Protecting GroupsEthers
8
Hydroxyl Protecting GroupsEthers
Hydroxyl Protecting GroupsSilyl Ethers
9
Hydroxyl Protecting GroupsSilyl Ethers
Hydroxyl Protecting GroupsSilyl Ethers
10
Hydroxyl Protecting GroupsSilyl Ethers
Silyl groups are typically deprotected with a source of fluoride ion.
The Si–F bond strength is about 30 kcal/mol stronger than the Si–O bond.
Hydroxyl Protecting GroupsSilyl Ethers
11
Hydroxyl Protecting GroupsSilyl Ethers
Hydroxyl Protecting GroupsSilyl Ethers
12
Hydroxyl Protecting GroupsEsters& Carbonates
Hydroxyl Protecting GroupsEsters & Carbonates
13
Hydroxyl Protecting GroupsEsters
In general, the susceptibility of esters to base catalyzed hydrolysis increases with the acidity of the product acid.
Hydroxyl Protecting GroupsEsters
14
Hydroxyl Protecting GroupsEsters
Hydroxyl Protecting GroupsEsters
15
Hydroxyl Protecting GroupsCarbonates
Hydroxyl Protecting GroupsCarbonates
16
Hydroxyl Protecting GroupsCarbonates
Hydroxyl Protecting GroupsPhenolic protective groups
17
Hydroxyl Protecting Groups1,2 and 1,3-diols
Hydroxyl Protecting Groups1,2 and 1,3-diols
18
Hydroxyl Protecting Groups1,2 and 1,3-diols
Hydroxyl Protecting Groups1,2 and 1,3-diols
Selective protection of polyols:
19
Hydroxyl Protecting Groups1,2 and 1,3-diols
Selective protection of polyols:
Hydroxyl Protecting Groups1,2 and 1,3-diols
Selective protection of polyols:
20
Hydroxyl Protecting Groups1,2 and 1,3-diols
Hydroxyl Protecting Groups1,2 and 1,3-diols
21
Hydroxyl Protecting Groups1,2 and 1,3-diols
Hydroxyl Protecting Groups1,2 and 1,3-diols
22
Hydroxyl Protecting Groups1,2 and 1,3-diols
Hydroxyl Protecting Groups1,2 and 1,3-diols
23
Carbonyl Protecting Groups
Carbonyl Protecting Groups
24
Carbonyl Protecting Groups
Carbonyl Protecting Groups
25
Carbonyl Protecting Groups
Carbonyl Protecting Groups
26
Carbonyl Protecting Groups
Carbonyl Protecting Groups
A variety of methods has been developed for the cleavage of S,S''-dialkyl acetals, largely due to the fact that these functional groups are often difficult to remove.
27
Carbonyl Protecting Groups
Carbonyl Protecting GroupsEsters for acid
28
Carbonyl Protecting GroupsEsters for acid
Carbonyl Protecting GroupsEsters for acid
29
Carbonyl Protecting GroupsEsters for acid
Carbonyl Protecting GroupsEsters for acid
30
Amine Protecting Groups
Alkyne Protecting Groups
31