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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.
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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.
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Hydroxyl Protecting GroupsAcetals
Hydroxyl Protecting GroupsAcetals
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Hydroxyl Protecting GroupsAcetals
Hydroxyl Protecting GroupsAcetals
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Hydroxyl Protecting GroupsAcetals
Hydroxyl Protecting GroupsAcetals
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Hydroxyl Protecting GroupsEthers
Hydroxyl Protecting GroupsEthers
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Hydroxyl Protecting GroupsEthers
Hydroxyl Protecting GroupsEthers
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Hydroxyl Protecting GroupsEthers
Hydroxyl Protecting GroupsSilyl Ethers
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Hydroxyl Protecting GroupsSilyl Ethers
Hydroxyl Protecting GroupsSilyl Ethers
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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
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Hydroxyl Protecting GroupsSilyl Ethers
Hydroxyl Protecting GroupsSilyl Ethers
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Hydroxyl Protecting GroupsEsters& Carbonates
Hydroxyl Protecting GroupsEsters & Carbonates
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Hydroxyl Protecting GroupsEsters
In general, the susceptibility of esters to base catalyzed hydrolysis increases with the acidity of the product acid.
Hydroxyl Protecting GroupsEsters
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Hydroxyl Protecting GroupsEsters
Hydroxyl Protecting GroupsEsters
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Hydroxyl Protecting GroupsCarbonates
Hydroxyl Protecting GroupsCarbonates
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Hydroxyl Protecting GroupsCarbonates
Hydroxyl Protecting GroupsPhenolic protective groups
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Hydroxyl Protecting Groups1,2 and 1,3-diols
Hydroxyl Protecting Groups1,2 and 1,3-diols
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Hydroxyl Protecting Groups1,2 and 1,3-diols
Hydroxyl Protecting Groups1,2 and 1,3-diols
Selective protection of polyols:
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Hydroxyl Protecting Groups1,2 and 1,3-diols
Selective protection of polyols:
Hydroxyl Protecting Groups1,2 and 1,3-diols
Selective protection of polyols:
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Hydroxyl Protecting Groups1,2 and 1,3-diols
Hydroxyl Protecting Groups1,2 and 1,3-diols
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Hydroxyl Protecting Groups1,2 and 1,3-diols
Hydroxyl Protecting Groups1,2 and 1,3-diols
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Hydroxyl Protecting Groups1,2 and 1,3-diols
Hydroxyl Protecting Groups1,2 and 1,3-diols
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Carbonyl Protecting Groups
Carbonyl Protecting Groups
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Carbonyl Protecting Groups
Carbonyl Protecting Groups
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Carbonyl Protecting Groups
Carbonyl Protecting Groups
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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.
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Carbonyl Protecting Groups
Carbonyl Protecting GroupsEsters for acid
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Carbonyl Protecting GroupsEsters for acid
Carbonyl Protecting GroupsEsters for acid
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Carbonyl Protecting GroupsEsters for acid
Carbonyl Protecting GroupsEsters for acid
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Amine Protecting GroupsGeneral Protecting Groups
Amine Protecting GroupsGeneral preparation
Bases that are typically employed are tertiary amines or aqueous hydroxide.
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Amine Protecting GroupsCarbamates
Amine Protecting GroupsCarbamates
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Amine Protecting GroupsCarbamates
Amine Protecting GroupsCarbamates
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Amine Protecting GroupsAmides
Amine Protecting GroupsSulfonamides
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Amine Protecting GroupsSulfonamides
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
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Alkyne Protecting Groups
Unpublished result of S. Kim