Elimination Reactions of Benzaldehyde O-Benzoyloximes 83
In this case, a high primary kinetic isotope effect (k H /k D ) and negligible effect of
the nucleofugacity of the leaving group should be expected.
Once we have discussed the main features of the E2, (E1cB) R and (E1cB)
R
irr mer
chanisms we are ready to determine which one is in better agreement with the experimental data obtained for substrates 1 and 2.
How can we decide among all these mechanisms?
Frequently, distinguishing among the various elimination mechanisms is not an
easy task, but careful analysis of the experimental data will give us the key in this
case. First, we know that the DBU-promoted eliminations in E- and Z-benz- Z Z
aldehyde O-benzoyloximes are general-base catalyzed reactions, that exhibit noticeable k H
k k /k
H H D
k k values (3.3 and 7.3) and significant extents of leaving group cleavage in the transition state (|E lg | 0.49 and 0.40) for E- and Z-isomers, respectively.
Z Z
The general catalysis and the high k H
k k /k
H H D
k k values are clearly incompatible with the
E1cB R mechanism, as we have commented ab
R
ove. On the other hand, the significant |E lg | values support a mechanism in which C-leaving group bond breaking occurs in the transition state (E2) but exclude the (E1cB) irr pathway.
r
In consequence, the bimolecular elimination (E2) seems to be the most appropriate
alternative for the DBU-promoted eliminations of oximes 1 and 2.
Once we have assumed that the E2 mechanism is the most suitable option for both
isomers, we have to explain why if compounds 1 and 2 share the same mechanism, they have different rates of elimination, Hammett U U U constants and k
d H
k k /k
H H D
k k values (see Table 12.1).
The first striking fact is the enormous disparity between the reaction rates.
Thus, the rate of elimination from Z-benzaldoxyme Z Z
2 is approximately 36,000-fold
faster than from E-benzaldoxyme 1. If we represent the E2 transition states for
oximes 1 and 2 we will realize that their structures are determined by the relative
arrangement of the H E and the benzoate groups in the starting compounds (Fig.
12.1).
The Z-isomer Z Z
2 is less stable than the E-isomer 1 due to the unfavorable steric
interactions between the bulky aryl and benzoate groups. It has been estimated
that the difference of stability between both isomers is 3.73 kcal/mol. However, as
we have discussed previously, in an E2 elimination process, the H E and the leaving
group depart simultaneously in the transition state. In the case of E-isomer 1, transition state 3 reveals that E2 elimination has to be syn: H E and the benzoate group
have to depart by the same side of the molecule. In the case of the less stable Z- Z Z
isomer 2, the elimination is anti: H E and the benzoate group departure occurs at
opposite sides of the molecule, as shown in transition state 4.
In this case, a high primary kinetic isotope effect (k H /k D ) and negligible effect of
the nucleofugacity of the leaving group should be expected.
Once we have discussed the main features of the E2, (E1cB) R and (E1cB)
R
irr mer
chanisms we are ready to determine which one is in better agreement with the experimental data obtained for substrates 1 and 2.
How can we decide among all these mechanisms?
Frequently, distinguishing among the various elimination mechanisms is not an
easy task, but careful analysis of the experimental data will give us the key in this
case. First, we know that the DBU-promoted eliminations in E- and Z-benz- Z Z
aldehyde O-benzoyloximes are general-base catalyzed reactions, that exhibit noticeable k H
k k /k
H H D
k k values (3.3 and 7.3) and significant extents of leaving group cleavage in the transition state (|E lg | 0.49 and 0.40) for E- and Z-isomers, respectively.
Z Z
The general catalysis and the high k H
k k /k
H H D
k k values are clearly incompatible with the
E1cB R mechanism, as we have commented ab
R
ove. On the other hand, the significant |E lg | values support a mechanism in which C-leaving group bond breaking occurs in the transition state (E2) but exclude the (E1cB) irr pathway.
r
In consequence, the bimolecular elimination (E2) seems to be the most appropriate
alternative for the DBU-promoted eliminations of oximes 1 and 2.
Once we have assumed that the E2 mechanism is the most suitable option for both
isomers, we have to explain why if compounds 1 and 2 share the same mechanism, they have different rates of elimination, Hammett U U U constants and k
d H
k k /k
H H D
k k values (see Table 12.1).
The first striking fact is the enormous disparity between the reaction rates.
Thus, the rate of elimination from Z-benzaldoxyme Z Z
2 is approximately 36,000-fold
faster than from E-benzaldoxyme 1. If we represent the E2 transition states for
oximes 1 and 2 we will realize that their structures are determined by the relative
arrangement of the H E and the benzoate groups in the starting compounds (Fig.
12.1).
The Z-isomer Z Z
2 is less stable than the E-isomer 1 due to the unfavorable steric
interactions between the bulky aryl and benzoate groups. It has been estimated
that the difference of stability between both isomers is 3.73 kcal/mol. However, as
we have discussed previously, in an E2 elimination process, the H E and the leaving
group depart simultaneously in the transition state. In the case of E-isomer 1, transition state 3 reveals that E2 elimination has to be syn: H E and the benzoate group
have to depart by the same side of the molecule. In the case of the less stable Z- Z Z
isomer 2, the elimination is anti: H E and the benzoate group departure occurs at
opposite sides of the molecule, as shown in transition state 4.