Lecture-Protecting Groups for Organic Synthesis

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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