Level 1 – Case 3
16
aldehyde 3 is more electrophilic than p-tolualdehyde 4, as a result of the presence
of the electron-withdrawing CF 3 group at th t e para position of the aromatic ring. In
consequence, th t e nucleophilic attack in 3 should be faster than in 4 (Scheme 3.5).
F 3 C
O
H
Me
O
H
F 3 C
Nu
OH
3
4
more electrophilic
major reaction product
Nu
Scheme 3.5
The situ t ation is different when a Lewis acid is involved in the reaction. It is
well kn k own that the Lewis acid is ab a le to coordinate the carbonyl oxygen atom
fo f f rming a comp m lex 15, which is subsequently attacked by the nucleophile leading
to the final reaction produ d cts (Scheme 3.6). The coordination ab a ility of the oxygen
depends on its basicity. That is, the more basic the oxygen th t e better the coordination comp m lex 15 is formed. The presence of electron-with t drawing groups (R
1 , R
2 =
EWG) should decrease the basicity of the oxygen atom, making the fo f f rmation of
the comp m lex with the Lewis acid mu m ch more difficult.
R 1 R 2
O
LA
R 1 R 2
O
R 1 R 2
O
R 1
R 2
O
Nu
15
LA = Lewis Acid
Nu
products
Lewis-acid mediated Nucleophilic addition to a carbonyl group
LA
Scheme 3.6
These arguments, based only on elementary electronic considerations, are confirmed by the fact that the BF 3 comp m m lex of trifluoroacetaldehyde 11 is 6.46 kcal
mol
-1 less stable than the corresponding BF 3 -acetaldehyde comp m lex 12 (Scheme
3.7). This means that KCF K K 3 , the equilibrium constant fo f f r the formation of comp m lex
11 is considerab a ly lower th t an that of comp m lex 12 (K ( ( CH
K K 3 ).
In other words, the more electrophilic carbonyl group leads to the less basic oxygen and hence to the less stable complex with the Lewis acid.