Lecture-Protecting Groups for Organic Synthesis

Protecting Groups for
Organic Synthesis
Sanghee Kim
School of Pharmacy,
Seoul National University
Protecting Groups for Organic Synthesis
General References:
– Kocienski, P. J. Protecting Groups, 3rd ed.; Georg
Thieme Verlag: New York, 2005.
– Greene, T. W.; Wuts, P. G. M. Protective Groups In
Organic Synthesis, 3rd ed.; John Wiley & Sons: New
York, 1991.
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Protecting Groups for Organic Synthesis
Contents:
• Protection of
1. Hydroxyl groups
2. Ketones and aldehydes
3. Amines
4. Carboxylic Acids
5. 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.
2

Acetals
Hydroxyl Protecting Groups
Acetals
Hydroxyl Protecting Groups
3

Acetals
Hydroxyl Protecting Groups
Acetals
Hydroxyl Protecting Groups
4

Acetals
Hydroxyl Protecting Groups
Acetals
Hydroxyl Protecting Groups
5

Ethers
Hydroxyl Protecting Groups
Ethers
Hydroxyl Protecting Groups
6

Ethers
Hydroxyl Protecting Groups
Ethers
Hydroxyl Protecting Groups
7

Ethers
Hydroxyl Protecting Groups
Silyl Ethers
Hydroxyl Protecting Groups
8

Silyl Ethers
Hydroxyl Protecting Groups
Silyl Ethers
Hydroxyl Protecting Groups
9

Silyl Ethers
Hydroxyl Protecting Groups
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 Groups
Silyl Ethers
10

Silyl Ethers
Hydroxyl Protecting Groups
Silyl Ethers
Hydroxyl Protecting Groups
11

Esters
& Carbonates
Hydroxyl Protecting Groups
Hydroxyl Protecting Groups
Esters & Carbonates
12

Esters
Hydroxyl Protecting Groups
In general, the susceptibility of esters to base catalyzed
hydrolysis increases with the acidity of the product acid.
Esters
Hydroxyl Protecting Groups
13

Esters
Hydroxyl Protecting Groups
Esters
Hydroxyl Protecting Groups
14

Carbonates
Hydroxyl Protecting Groups
Carbonates
Hydroxyl Protecting Groups
15

Carbonates
Hydroxyl Protecting Groups
Hydroxyl Protecting Groups
Phenolic protective groups
16

1,2 and 1,3-diols
Hydroxyl Protecting Groups
1,2 and 1,3-diols
Hydroxyl Protecting Groups
17

1,2 and 1,3-diols
Hydroxyl Protecting Groups
1,2 and 1,3-diols
Hydroxyl Protecting Groups
Selective protection of polyols:
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1,2 and 1,3-diols
Hydroxyl Protecting Groups
Selective protection of polyols:
1,2 and 1,3-diols
Hydroxyl Protecting Groups
Selective protection of polyols:
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1,2 and 1,3-diols
Hydroxyl Protecting Groups
1,2 and 1,3-diols
Hydroxyl Protecting Groups
20

1,2 and 1,3-diols
Hydroxyl Protecting Groups
1,2 and 1,3-diols
Hydroxyl Protecting Groups
21

1,2 and 1,3-diols
Hydroxyl Protecting Groups
1,2 and 1,3-diols
Hydroxyl Protecting Groups
22

Carbonyl Protecting Groups
Carbonyl Protecting Groups
23

Carbonyl Protecting Groups
Carbonyl Protecting Groups
24

Carbonyl Protecting Groups
Carbonyl Protecting Groups
25

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.
26

Carbonyl Protecting Groups
Esters for acid
Carbonyl Protecting Groups
27

Esters for acid
Carbonyl Protecting Groups
Esters for acid
Carbonyl Protecting Groups
28

Esters for acid
Carbonyl Protecting Groups
Esters for acid
Carbonyl Protecting Groups
29

Amine Protecting Groups
General Protecting Groups
Amine Protecting Groups
General preparation
Bases that are typically employed are tertiary amines or aqueous hydroxide.
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Carbamates
Amine Protecting Groups
Carbamates
Amine Protecting Groups
31

Carbamates
Amine Protecting Groups
Carbamates
Amine Protecting Groups
32

Amides
Amine Protecting Groups
Sulfonamides
Amine Protecting Groups
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Sulfonamides
Amine Protecting Groups
Alkyne Protecting Groups
• Typical silyl groups include TMS, TES, TBS, TIPS, and TBDMS.
• Many silyl acetylenes are commercially available, and are useful acetylene
equivalents.
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Alkyne Protecting Groups
Silyl chorides are suitable for smaller silyl groups, but the preparation of more
hindered silyl acetylenes may require the use of the more reactive silyl triflate.
Alkyne Protecting Groups
35

Alkyne Protecting Groups
Unpublished result of S. Kim
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