Organic Chemistry

PROBLEM 35

Which enantiomer is formed when a methyl Grignard reagent attacks the Reface of each

of the following carbonyl compounds?

a. propiophenone c. 2-pentanone

b. benzaldehyde d. 3-hexanone

18.12 Designing a Synthesis V: Disconnections,

Synthons, and Synthetic Equivalents

The synthesis of a complicated molecule from simple starting materials is not always

obvious. We have seen that it is often easier to work backward from the desired product

to available starting materials—a process called retrosynthetic analysis(Section 6.11).

In a retrosynthetic analysis, the chemist dissects a molecule into smaller and smaller

pieces until readily available starting materials are obtained.

A useful step in a retrosynthetic analysis is a disconnection—breaking a bond to

produce two fragments. Typically, one fragment is positively charged and one is nega-

tively charged. The fragments of a disconnection are called synthons. Synthons are

often not real compounds—they can be imaginary species. For example, if we consid-

er the retrosynthetic analysis of cyclohexanol, we see that a disconnection gives two

synthons—an -hydroxycarbocation and a hydride ion.

A synthetic equivalentis the reagent that is actually used as the source of the synthon.

Cyclohexanone is the synthetic equivalent for the -hydroxycarbocation, and sodium

borohydride is the synthetic equivalent for hydride ion. Thus, cyclohexanol, the target

molecule, can be prepared by treating cyclohexanone with sodium borohydride.

a

retrosynthetic analysis

a disconnection

HO H OH

+ H−

+

open arrow represents a

retrosynthetic operation

synthons

a

retrosynthetic analysis

target moleculeYXWstarting materials

766 CHAPTER 18 Carbonyl Compounds II

ENZYME-CATALYZED

CARBONYL ADDITIONS

In an enzyme-catalyzed addition to a carbonyl

compound, only one of the enantiomers is formed. The enzyme

can block one face of the carbonyl compound so that it cannot

be attacked, or it can position the nucleophile so that it is able to

attack the carbonyl group from only one side of the molecule.

C O

nucleophile

Because the carbonyl carbon and the three atoms attached to it define a plane, the

Reand Sifaces have an equal probability of being attacked. Consequently, an addition

reaction forms equal amounts of the two enantiomers.