The document discusses the concept of protection and deprotection in chemical reactions, emphasizing the need to temporarily block reactive sites in multifunctional compounds to achieve selectivity. It describes requirements for a protecting group, noting the use of hydroxyl-protective groups like the tetrahydropyranyl (thp) ether, which can be introduced via acid-catalyzed addition. The text highlights the method of deprotection through mildly acidic hydrolysis and mentions potential complications in using chiral alcohols.

1. Protection and Deprotection
When a chemical reaction is to be carried out
selectively at one reactive site in a multifunctional
compound, other reactive sites must be temporarily
blocked; this action is called protection of functional
group.

3. A protecting group must fulfill a
number of requirements
The protecting group reagent must react selectively
(kinetic chemoselectivity) in good yield to give a
protected substrate that is stable to the projected
reactions.
• The protecting group must be selectively
removed in good yield by readily available
reagents.
• The protecting group should not have additional
functionality that might provide additional sites
of reaction.

12. Hydroxyl-Protective Groups
A common requirement in synthesis is that a hydroxyl group be masked as
a derivative lacking a hydroxylic proton. An example of this requirement is
in reactions involving Grignard or other organometallic reagents.
Conversion to an alkyl or silyl ehter is the most common means of protecting
hydroxyl group.
Mildly acidic hydrolysis is an appropriate method for deprotection
(dilute aqueous acid)
(THP; tetrahydropyranyl
ether)

13. THP group is introduced by an acid-catalyzed addition of the alcohol to the
vinyl ether in dihydropyran. (catalyst: p-toluenesulfonic acid or its pyridinium salt)
THP group: inert to nucleophilic reagent and unchanged under hydride reduction,
organometallic reactions, oxidation, or base-catalyzed reactions in aqueous
solution,
Disadvantage: a stereogenic center is produced at C-2 of the THP ring.
If the alcohol is chiral, the reaction will give a mixture of diastereomeric ethers,
which may complicate purification and characterization.

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