Level 1 – Case 4
24
O
R
1
TiCl 4
OR 3
O
R 2
H
H
O
R 1
TiCl 4
OR 3
O
H
R 1
OR 3
OH
R 2
O
R 2
TiCl 4
R 1
OR 3
O
R 2
O
5
syn-2
1
anti-3
H
Scheme 4.2
The formation of the chelates between E-ketoesters 1 and TiCl 4 is favored in a
non-coordinating solvent such as CH 2 Cl 2 but is more difficult when coordinating
solvents like THF or Et 2 O are employed.
1 In such cases the stereochemical control
due to the formation of the chelation products with the Lewis acid is lost.
The stereochemistry of the reaction products is reversed when the poor chelating Lewis acid CeCl 3 is employed. In this case, an open-chain Felkin-Anh’s model
is the most adequate to justify the anti-selectivity observed during the reduction of
E-ketoesters 1. The first step of the reaction should be the coordination of the
CeCl 3 with the oxygen atom. As indicated in the Scheme 4.3, the 1-CeCl 3 complex
can be represented as equilibrium between conformations 6 and 7. Invoking the
Bürgi-Dunitz trajectory, the attack to the conformation 6 should be preferred by
steric effects, leading to the anti-alcohol 3 as the major reaction product (anti
means that the OH and the R
2
R R group are on opposite sides of the molecule on staggered conformation).
1 The donor numbers (DN ( (
kcal mol
N
-1 ) are a measure of the coordinating ability of a solvent. They have been defined as the negative 'H values for 1:1-adduct formation between antimony pentachloride and an electron pair donor solvent (D) in dilute solution of
a non-coordinating solvent (1,2-dichloroethane), according with Eq. 4.1.
D SbCl 5
D: + SbCl 5
(4.1)
24
O
R
1
TiCl 4
OR 3
O
R 2
H
H
O
R 1
TiCl 4
OR 3
O
H
R 1
OR 3
OH
R 2
O
R 2
TiCl 4
R 1
OR 3
O
R 2
O
5
syn-2
1
anti-3
H
Scheme 4.2
The formation of the chelates between E-ketoesters 1 and TiCl 4 is favored in a
non-coordinating solvent such as CH 2 Cl 2 but is more difficult when coordinating
solvents like THF or Et 2 O are employed.
1 In such cases the stereochemical control
due to the formation of the chelation products with the Lewis acid is lost.
The stereochemistry of the reaction products is reversed when the poor chelating Lewis acid CeCl 3 is employed. In this case, an open-chain Felkin-Anh’s model
is the most adequate to justify the anti-selectivity observed during the reduction of
E-ketoesters 1. The first step of the reaction should be the coordination of the
CeCl 3 with the oxygen atom. As indicated in the Scheme 4.3, the 1-CeCl 3 complex
can be represented as equilibrium between conformations 6 and 7. Invoking the
Bürgi-Dunitz trajectory, the attack to the conformation 6 should be preferred by
steric effects, leading to the anti-alcohol 3 as the major reaction product (anti
means that the OH and the R
2
R R group are on opposite sides of the molecule on staggered conformation).
1 The donor numbers (DN ( (
kcal mol
N
-1 ) are a measure of the coordinating ability of a solvent. They have been defined as the negative 'H values for 1:1-adduct formation between antimony pentachloride and an electron pair donor solvent (D) in dilute solution of
a non-coordinating solvent (1,2-dichloroethane), according with Eq. 4.1.
D SbCl 5
D: + SbCl 5
(4.1)