A Quick Recap on Protecting Groups

Three Steps Required:

1. Hide the incompatible group
2. Do what needs to be done elsewhere
in the molecule
3. Remove the protecting group and
return to the original group

Two protecting groups for alcohols:

Trimethylsilyl ether formation using
trimethylsilyl chloride (TMS-Cl) and
triethylamine (NEt3)
Easily removed by aqueous acid
(H3O+) or FT M S-C l
R -O -T M S
R -O -H
N Et3

Two protecting groups for alcohols:

Dihydropyran (DHP) and an acid
catalyst (H+) will react to form a
tetrahydropyran protecting group
(THP)
Easily removed by aqueous acid
(H3O+)
DHP, H+

R -O -H

R -O -T H P

For more than one alcohol

remember that there is an order in
which
alcohols
are
protected,
beginning with primary alcohols
(least sterically hindered), then
secondary alcohols (more sterically
hindered) and1 finally
e q u iv . T M S - C l tertiary alcohols
OH

OH

N Et3

O TM S

OH

 In most cases, when working with a

single alcohol that needs to be
protected, the two groups are
INTERCHANGEABLE so it doesnt
matter which ones you use
OH
OH

1 e q u iv . D H P
H+

O TH P
OH

 Sometimes
you
will
need
to
manipulate two alcohols if you
need to protect them both so they
are both out of the way, use the
same one
HO

OH
OH

2 e q u iv . D H P
H+

THPO

O TH P
OH

 Remember the order for protecting

alcohols is always going to show
reaction on the 1, then 2 and then
3:
HO

Thus:

OH
OH

2 e q u iv . D H P
H+

THPO

OH
O THP

 Those problems that require you to

protect the less hindered alcohol first
are easier than those where the less
hindered alcohol is the one you NEED
for the chemistry
Example:

OH
OH

OH
O

Quick and simple to protect the

primary alcohol so the secondary can
be oxidized, right?

 Right!
OH
OH

1 e q u iv . D H P
H+

O TH P
OH

PCC

OH
OH

H 3O +

O TH P
O

 When the the primary alcohol is the one

you NEED for the chemistry, you will have
to actually protect it FIRST and then use a
different protecting group on the secondary
alcohol and deprotect the first alcohol so
you can do your chemistry on it
O
OH
OH

H
OH

Be sure to use two protecting groups that

can be taken off with different reagents

 For
alcohols,
you
have
TWO
protecting groups to use - one that
comes off with aqueous acid and one
that comes off with aqueous acid OR
fluoride anion
Just be sure not to START with the
one that has to be removed using
the
O
SAME reagent
O H as the second one
H
OH

OH

 Using TMS-Cl, NEt3 first and then

DHP, H+ allows you to remove the
TMS group easily with F-, thus
allowing the THP
in place:
1 e q to
u iv . T Mstay
S-C l
OH
O TM S
N E t3

OH

OH

DHP, H+

OH
O TH P

HF

O TM S
O TH P

 Using DHP, H+ first and then TMS-Cl,

NEt3 wont allow you to remove the
THP group easily without also
removing the1 e TMS
group:
q u iv . D H P
OH

O TH P

H+

OH

OH

T M S - C l, N E t 3
OH
OH

H 3O +

O TH P
O TM S

 And hopefully you recognize that if

you put the same protecting group
on both alcohols, you cannot
selectively REMOVE one over the
2 e q u iv . D H P
OH
O TH P
other:O H
H+
O THP

H 3O +
OH
OH

 This concludes our review of alcohol

protecting groups.
Hopefully it
helped eliminate any questions that
may have been left in your mind
after lecture.