Level 3 – Case 32
216
tion state. This is in agreement with the mechanism proposed in Scheme 32.4, in
which two successive bond formation steps take place from the reagents to the activated complex in the rate-determining step.
2
The Baylis-Hillman reaction is accompanied by a considerable reduction in
volume and it is evident that an increase in pressure would accelerate the reaction.
For example, with an increase of pressure from 1 bar to 1000 bar, a 15-fold increase in the value of k obs
k k was observed. The effect of pressure has been used to
extend the limited scope of the Baylis-Hillman reaction. In fact E-substituted acrylates (unreactive at atmospheric pressure) give the Baylis-Hillman products under
high pressure conditions (8 kbar) in reasonable yields.
In Summary
The Baylis-Hillman reaction is generally defined as a base-catalyzed reaction between an DE-unsaturated carbonyl compound and an aldehyde. However, the experimental evidence clearly demonstrates that the catalyst is involved in the reaction as a nucleophile, not as a base. The steps of the process include the conjugate addition of the catalyst to the DE-unsaturated carbonyl compound, addition
to the aldehyde, and elimination. The reaction has a very high volume of activation and the rate is very sensitive to an increase in pressure.
Additional Comments
This problem is based on the work by: (a) Hill JS, Isaacs NS (1990) J. Phys. Org.
Chem. 3:285-288. (b) van Rozendaal ELM, Voss BMW, Scheeren HW (1993)
Tetrahedron 49:6931-6936. (c) Iwabuchi Y, Nakatani M, Yokoama N, Hatakeyama S (1999) J. Am. Chem. Soc. 121:10219-10220.
Subjects of Revision
Nucleophile catalysis. Base catalysis. Volume of activation.
2 Diels-Alder reactions are known to have high 'V
‡ values as they are accompanied by a
considerable reduction in volume. In such processes two molecules are combining to a
single product, though no charges are involved. The typical 'V
‡ values are about –35 cm
3
mol
–1 . However, it is a fact that associative processes leading to ion formation, have
much larger volumes of activation due to solvent electrostriction (that is, the tendency
of a solvent to associate tighly with a charged center by electrostatic forces). The solvent
electrostriction is responsible for a reduction of both, entropy and volume of activation
and has been claimed to be responsible for the high magnitude of 'V
‡ observed in this
case.
216
tion state. This is in agreement with the mechanism proposed in Scheme 32.4, in
which two successive bond formation steps take place from the reagents to the activated complex in the rate-determining step.
2
The Baylis-Hillman reaction is accompanied by a considerable reduction in
volume and it is evident that an increase in pressure would accelerate the reaction.
For example, with an increase of pressure from 1 bar to 1000 bar, a 15-fold increase in the value of k obs
k k was observed. The effect of pressure has been used to
extend the limited scope of the Baylis-Hillman reaction. In fact E-substituted acrylates (unreactive at atmospheric pressure) give the Baylis-Hillman products under
high pressure conditions (8 kbar) in reasonable yields.
In Summary
The Baylis-Hillman reaction is generally defined as a base-catalyzed reaction between an DE-unsaturated carbonyl compound and an aldehyde. However, the experimental evidence clearly demonstrates that the catalyst is involved in the reaction as a nucleophile, not as a base. The steps of the process include the conjugate addition of the catalyst to the DE-unsaturated carbonyl compound, addition
to the aldehyde, and elimination. The reaction has a very high volume of activation and the rate is very sensitive to an increase in pressure.
Additional Comments
This problem is based on the work by: (a) Hill JS, Isaacs NS (1990) J. Phys. Org.
Chem. 3:285-288. (b) van Rozendaal ELM, Voss BMW, Scheeren HW (1993)
Tetrahedron 49:6931-6936. (c) Iwabuchi Y, Nakatani M, Yokoama N, Hatakeyama S (1999) J. Am. Chem. Soc. 121:10219-10220.
Subjects of Revision
Nucleophile catalysis. Base catalysis. Volume of activation.
2 Diels-Alder reactions are known to have high 'V
‡ values as they are accompanied by a
considerable reduction in volume. In such processes two molecules are combining to a
single product, though no charges are involved. The typical 'V
‡ values are about –35 cm
3
mol
–1 . However, it is a fact that associative processes leading to ion formation, have
much larger volumes of activation due to solvent electrostriction (that is, the tendency
of a solvent to associate tighly with a charged center by electrostatic forces). The solvent
electrostriction is responsible for a reduction of both, entropy and volume of activation
and has been claimed to be responsible for the high magnitude of 'V
‡ observed in this
case.