Base-promoted HF Elimination from 4-Fluoro-4-(4’-nitrophenyl)butan-2-one 249
The secondary D KIEs for substrate 4 are 1.009, 1.000 and 1.010 for formate,
acetate and imidazole, respectively. Except for imidazole, these values are smaller
than those obtained by the standard method (1.038, 1.050 and 1.014). This would
indicate that the breakage of the C3-H bond and the hybridization change at C4
(from sp
3 to sp
2 ) occur in different steps. Alternatively, the leaving group F KIE
for deuterated substrate 6 (1.0009) is considerable smaller than the one previously
recorded (1.0047). Again, this result could indicate that the breakage of the C3-H
bond and the departure of the fluorine leaving group take place in different steps
of the reaction. Both arguments are definitively pointing to a stepwise mechanism
and not to a concerted one, even if this is not very symmetrical. In consequence,
the stepwise (E1cB) irr mechanism seems to be the most likely for the elimination
of substrates 1 (Scheme 37.3).
O
F
O 2 N
H H
O
F
O 2 N
O
O 2 N
F
(E1cB) irr
k 1
k 2
k k
base
slow
1
2
Scheme 37.3
As usual, before making a final conclusion we should test if the proposed
mechanism fits well with all the experimental data. First, the elimination rate is affected by an increase in the base character. In the (E1cB) irr mechanism the first
step is rate-limiting and the stronger the base the easier the removal of the acidic
C3 hydrogen (k 1 ). In addition, a noticeable primary KIE must be observed at this
position. The size of primary deuterium KIEs for proton transfer processes are
considered as a measure of the symmetry of the transition state for the transfer. In
f
this case, the highest value (7.5, the maximum calculated value for a primary KIE)
corresponds to the stronger base (imidazol), which indicates a central transition
l
state having the proton bounded with equal strength to C3 and base (A in Fig.
37.5). Weaker bases (formate, acetate) lead to less symmetrical transition states
and hence to smaller KIEs (B in Fig. 37.5). Finally, secondary D KIEs at C4 and F
KIEs are very small, as these bonds are not broken in the slow step of the reaction
(k 2
k k ).
D
*F
COCH 3
Ar D
D
*F
COCH 3
Ar D
A
B
base
G
base b
G
Figure 37.5
The secondary D KIEs for substrate 4 are 1.009, 1.000 and 1.010 for formate,
acetate and imidazole, respectively. Except for imidazole, these values are smaller
than those obtained by the standard method (1.038, 1.050 and 1.014). This would
indicate that the breakage of the C3-H bond and the hybridization change at C4
(from sp
3 to sp
2 ) occur in different steps. Alternatively, the leaving group F KIE
for deuterated substrate 6 (1.0009) is considerable smaller than the one previously
recorded (1.0047). Again, this result could indicate that the breakage of the C3-H
bond and the departure of the fluorine leaving group take place in different steps
of the reaction. Both arguments are definitively pointing to a stepwise mechanism
and not to a concerted one, even if this is not very symmetrical. In consequence,
the stepwise (E1cB) irr mechanism seems to be the most likely for the elimination
of substrates 1 (Scheme 37.3).
O
F
O 2 N
H H
O
F
O 2 N
O
O 2 N
F
(E1cB) irr
k 1
k 2
k k
base
slow
1
2
Scheme 37.3
As usual, before making a final conclusion we should test if the proposed
mechanism fits well with all the experimental data. First, the elimination rate is affected by an increase in the base character. In the (E1cB) irr mechanism the first
step is rate-limiting and the stronger the base the easier the removal of the acidic
C3 hydrogen (k 1 ). In addition, a noticeable primary KIE must be observed at this
position. The size of primary deuterium KIEs for proton transfer processes are
considered as a measure of the symmetry of the transition state for the transfer. In
f
this case, the highest value (7.5, the maximum calculated value for a primary KIE)
corresponds to the stronger base (imidazol), which indicates a central transition
l
state having the proton bounded with equal strength to C3 and base (A in Fig.
37.5). Weaker bases (formate, acetate) lead to less symmetrical transition states
and hence to smaller KIEs (B in Fig. 37.5). Finally, secondary D KIEs at C4 and F
KIEs are very small, as these bonds are not broken in the slow step of the reaction
(k 2
k k ).
D
*F
COCH 3
Ar D
D
*F
COCH 3
Ar D
A
B
base
G
base b
G
Figure 37.5