Organic Chemistry

PROBLEM 32

Give the product of the reaction of each of the following compounds with a base:

a. c.

b. d.

The Robinson Annulation
Reactions that form carbon–carbon bonds are important to synthetic chemists. Without
such reactions, large organic molecules could not be prepared from smaller ones. We
have seen that Michael reactions and aldol additions form carbon–carbon bonds. The
Robinson annulationis a reaction that puts these two carbon–carbon bond-forming
reactions together, providing a route to the synthesis of many complicated organic mole-
cules. “Annulation”comes from annulus, Latin for “ring.”Thus, an annulation reaction
is a ring-forming reaction.
The first stage of a Robinson annulation is a Michael reaction that forms a 1,5-dike-
tone. You just saw that a 1,5-diketone undergoes an intramolecular aldol addition
when treated with base—this is the second stage of the Robinson annulation. Notice
that a Robinson annulation results in a product that has a 2-cyclohexenone ring.

PROBLEM-SOLVING STRATEGY

Propose a synthesis for each of the following compounds, using a Robinson annulation:

By analyzing a Robinson annulation, we will be able to determine which part of the mole-

cule comes from which reactant. This, then, will allow us to choose appropriate reactants

for any other Robinson annulation. Analysis shows that the keto group of the cyclo-

hexenone comes from the carbonyl compound and the double bond

results from attack of the enolate of the carbonyl compound on the

carbonyl group of the other reactant. Thus, we can arrive at the appropriate reactants by

cutting through the double bond and cutting between the and on the other

side of the carbonyl group.

b- g-carbons

a,b-unsaturated

a,b-unsaturated

O

CH 3

a. b.

O

CH 3

O

CH 2 CH 2 CH 2 CCH 3

O

O

O

OO

HCCH 2 CH 2 CH 2 CH 2 CH 2 CH

O

CH 2 CH 2 CCH 3

O

Section 19.16 Intramolecular Condensation and Addition Reactions 817

Sir Robert Robinson (1886–1975)

was born in England, the son of a

manufacturer. After receiving a Ph.D.

from the University of Manchester, he

joined the faculty at the University of

Sydney in Australia. He returned to

England three years later, becoming

a professor of chemistry at Oxford in

1929. Robinson was an accomplished
      mountain climber. Knighted in 1939,
      he received the 1947 Nobel Prize in
      chemistry for his work on alkaloids.

Tutorial:

Robinson annulation—

synthesis

CH 3

HO− HO−

O

O O O O

O

CH 2 CHCCH 3

∆

OH

C

+

a Michael

reaction

the Robinson annulation

an intramolecular

aldol addition

+ H 2 O