Section 19.13 The Mixed Aldol Addition 809lose a proton from an to form enolates and can react with either
A or B, and can react with either A or B:
The preceding reaction is called a mixed aldol additionor a crossed aldol addition.
The four products have similar physical properties, making them difficult to separate.
Consequently, a mixed aldol addition that forms four products is not a synthetically
useful reaction.
Under certain conditions, a mixed aldol addition can lead primarily to one product. If
one of the carbonyl compounds does not have any it cannot form an eno-
late. This reduces the number of possible products from four to two. A greater amount
of one of the two products will be formed if the compound without is al-
ways present in excess, because the enolate will be more likely to react with it, rather
than with another molecule of the carbonyl compound from which the enolate was
formed, if there is more of the compound without in solution. Therefore,
the compound with should be added slowly to a basic solution of the com-
pound without
If both carbonyl compounds have primarily one aldol product can be
obtained if LDA is used to remove the that creates the enolate. Because
LDA is a strong base (Section 19.7), all the carbonyl compound will be converted into
an enolate, so there will be no carbonyl compound left with which the enolate could
react in an aldol addition. An aldol addition will not be able to occur until the second
carbonyl compound is added to the reaction mixture. If the second carbonyl compound
is added slowly, the chance that it will form an enolate and then react with another
molecule of its parent carbonyl compound will be minimized.
LDA- CH 3 CH 2 CH 2 CH
add slowly
O- H 2 O
O O OOHCHCH 2 CH 2 CH 3
−a-hydrogena-hydrogens,a-hydrogens.a-hydrogensa-hydrogensa-hydrogensa-hydrogens,B-a-carbon A- B-;A-H 2 OH 2 OCH 3CH 3CH 3ABA−B−BABAHO−HO−H 2 O
HO−H 2 O
HO−H 2 O
HO−H 2 O
HO−O OCH 3 CH 2 CH CH 3 CHCH 2 CHOCH 3 CHCH
O− OCH 3 CHCH 2 CHCH 3CHCHCH 3OH OCH 3 CHCH 2 CHCH 3CHCHCH 3OH OCH 3 CHCH 2 CHCHCH 3CH 3CHCHO− OCH 3 CH 2 CHCH 3CHCHOH OCH 3 CH 2 CHCH 3CHCHCH 3O− OCH 3 CHCH 2 CHCHCH 3CH 3CHCHO− OCH 3 CH 2 CHCHCH 3CH 3CHCHOH OCH 3 CH 2 CHCHCH 3CH 3CHCHOCH 3 CHCHCH+−−O OCHHO−excess add slowly+ CH 3 CH 2 CH 2 CH +OH OCH CHCHCH 2 CH 3OCH CCH H 2 OCH 2 CH 3Tutorial:
Aldol reactions—synthesis