Organic Chemistry

824 CHAPTER 19 Carbonyl Compounds III

19.20 Designing a Synthesis VI:

Making New Carbon–Carbon Bonds

When you are planning the synthesis of a compound that requires the formation of a

new carbon–carbon bond, first locate the new bond that must be made. For example, in

the synthesis of the following the new bond is the one that makes the

second five-membered ring:

Next, determine which of the atoms that form the bond should be the nucleophile

and which should be the electrophile. In this case, it is easy to choose between the two

possibilities because you know that a carbonyl carbon is an electrophile.

Now you need to determine what compound you could use that would give you the

desired electrophilic and nucleophilic sites. If the starting material is indicated, use it

as a clue to arrive at the desired compound. For example, an ester carbonyl group

would be a good electrophile for this synthesis because it has a group that would be

eliminated. Furthermore, the of the ketone are more acidic than the

of the ester, so it would be easy to obtain the desired nucleophile. The

ester can be easily prepared from the carboxylic acid starting material.

In the next synthesis, two new carbon–carbon bonds must be formed.

After determining the electrophilic and nucleophilic sites, you can see that two suc-

cessive alkylations of a diester of malonic acid, using 1,5-dibromopentane for the

alkyl halide, will produce the desired compound.

CH 3 O OCH 3

OO

CH 3 O OCH 3

OO

?

a-hydrogens

a-hydrogens

CH 3

CH 3

CH 3

CH 3

or

O

O

− +

O

O

+−

nucleophile

electrophile

electrophile

nucleophile

O

O

O

O

CH 3

CH 3

CH 3

CH 3

CH 2 CH 2 COH

new bond

?

b-diketone,

Tutorial:

Retrosynthesis

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

1. SOCl 2 1. CH 3 O−


2. CH 3 OH 2. H 3 O+

O

O

OO

O

CH 2 CH 2 COCH 3

O

CH 2 CH 2 COH