Organic Chemistry

Section 18.13 Nucleophilic Addition to a,b-Unsaturated Aldehydes and Ketones 771

Like hydride ions, Grignard reagents add irreversibly to carbonyl groups. There-
fore, Grignard reagents react with -unsaturated aldehydes and unhindered -
unsaturated ketones to form direct addition products.

If, however, the rate of direct addition is slowed down by steric hindrance, a Grignard
reagent will form a conjugate addition product because conjugate addition then
becomes the faster reaction.

Only conjugate addition occurs when Gilman reagents (lithium dialkylcuprates,
Section 12.12) react with -unsaturated aldehydes and ketones. Therefore, Gri-
gnard reagents should be used when you want to add an alkyl group to the carbonyl
carbon, whereas Gilman reagents should be used when you want to add an alkyl
group to the

Electrophiles and nucleophiles can be classified as either hardor soft. Hard elec-
trophiles and nucleophiles are more polarized than soft ones. Hard nucleophiles prefer
to react with hard electrophiles, and soft nucleophiles prefer to react with soft elec-
trophiles. Therefore, a Grignard reagent with a highly polarized bond prefers
to react with the harder bond, whereas a Gilman reagent with a much less po-
larized bond prefers to react with the softer bond.

PROBLEM 37

Give the major product of each of the following reactions:

a. c.

b. d.

PROBLEM 38

Which would give a higher yield of an unsaturated alcohol when treated with sodium boro-

hydride, a sterically hindered ketone or a nonsterically hindered ketone?

1. (CH 3 ) 2 CuLi


2. H 3 O+

CH 3 O

CH 3 C CHCCH 3

1. NaBH 4


2. H 3 O+
   O


3. CH 3 MgBr


4. H 3 O+

CH 3 O

CH 3 C CHCCH 3

−CN

HCl

O

C¬Cu C“C

C“O

C¬Mg

1. CH 3 MgBr


2. H 3 O+

HO CH 3

CH 3

O

1. (CH 3 ) 2 CuLi


2. H 3 O+

O O

b-carbon.

a,b

O

C

1. C 6 H 5 Li

CH 2 2. H^3 O+

O

CH CH 2 CH 2

C

O

H

C

OH

1. CH 3 MgBr CH 2 CH CHCH 3
   CH 2 CH 2. H 3 O+

a,b a,b

O OH

99%

1. NaBH 4 , CeCl 3


2. EtOH