Organic Chemistry

Section 18.8 Protecting Groups 759

PROBLEM 29

a. What would have been the product of the preceding reaction with if the keto

group had not been protected?

b. What reagent could you use to reduce only the keto group?

PROBLEM 30

Why don’t acetals react with nucleophiles?

In the following reaction, the aldehyde reacts with the diol because aldehydes are
more reactive than ketones. The Grignard reagent will now react only with the keto
group. The protecting group can be removed by acid-catalyzed hydrolysis.

One of the best ways to protect an OH group of an alcohol is to convert it to a
trimethylsilyl (TMS) ether by treating the alcohol with chlorotrimethylsilane and a ter-
tiary amine. The ether is formed by an reaction. Although a tertiary alkyl halide
does not undergo an reaction, the tertiary silyl compound does because
bonds are longer than bonds, reducing steric hindrance at the site of nucleo-
philic attack. The amine prevents the solution from becoming acidic by reacting with
the HCl generated in the reaction. The TMS ether, which is stable in neutral and basic
solutions, can be removed with aqueous acid under mild conditions.

The OH group of a carboxylic acid group can be protected by converting the car-
boxylic acid into an ester.

C¬C

SN 2 Si¬C

SN 2

LiAlH 4

COCH 3 CH 2 O− CH 2 OH

HCl LiAlH 4 HCl, H 2 O

O O O

+ HOCH 2 CH 2 OH

+ HOCH 2 CH 2 OH

COCH 3

O

OO OO

protecting

group

OH

H

HCl

HOCH 2 CH 2 CH 2 OH 2. HCl, H 2 O

1. CH 3 MgBr

O

O

O

OH OH

+ HOCH 2 CH 2 CH 2 OH

+

O

H

O

O

H

(CH 3 CH 2 ) 3 NCH 3 MgBr H 3 O+

O

OH

CH 3

CH 3

CH 3

+ Si Cl

OSi(CH 3 ) 3 OSi(CH 3 ) 3

O

HO

OH

CH 3

−OCH

3

protecting

group

chlorotrimethylsilane a trimethylsilyl ether

a TMS ether

MgBr

+