Base-promoted HF Elimination from 4-Fluoro-4-(4’-nitrophenyl)butan-2-one 245
If the two labeled positions of the substrates 4 and 6 are involved in different
steps of the mechanism, the deuteration at C3 slows down its own step but also
makes the subsequent steps slower, decreasing the observed size of the evaluated KIE. However, if the two isotopes are involved in the same step of the reaction the observed KIE can be enhanced (this step has become slower and thus
more rate-limiting) or alternatively shows no change (if the step was in fact ratelimiting).
6. The C4-secondary deuterium KIEs obtained from the double-isotopic fractionation method in substrates 3 and 4 were 1.009, 1.000 and 1.010, for formate,
acetate and imidazole, respectively.
The F KIE in substrates 5 and 6 was exclusively determined in presence of acetate
as base. The observed value was 1.0009.
D Di is sc cu us ss si io on n
Base-promoted E-eliminations can be E1, E2 and E1cB. In our case, the E1 mechanism would consist of the rate-limiting detachment of the fluorine leaving
group followed by a base-promoted fast proton-transfer step (equation A in
Scheme 37.2). In the E2 mechanism the bond breakage of the proton being transferred to the base and the detachment of the fluorine-leaving group are concerted
(equation B in Scheme 37.2). Finally, the E1cB mechanism consists of a proton
transfer step that leads to the formation of a carbanion intermediate, followed by
the departure of the leaving group (equation C in Scheme 37.2). Depending on the
rate-determining step of the reaction, we can distinguish between different types
of E1cB mechanisms. If the slow step is the formation of the carbanion intermediate (step 1 in equation C) the elimination is called (E1cB) irr . However, if the ratedetermining step of the reaction is the departure of the leaving group (step 2 on
equation C) the reaction is called (E1cB) R .
With the help of the kinetic isotope data we should be able to distinguish between the different options. Deuterium KIEs at C3 indicate the degree of bond
breakage of the C3-H bond, deuterium KIEs at C4 reflect the degree of rehybridization at the according position and the F KIEs are a measure of the breakage of
the C-F bond. All are obviously referred to the transition state of the slow step of
the reaction.
The experimental data in Table 37.1 indicate a primary deuterium KIE at C3 in
all cases studied. This result definitively rules out the E1 mechanism, as the
breakage of the C3-H bond does not occur during the rate-determining step. As we
can see in the E1 transition state represented in Fig. 37.2, the C-F bond is being
broken but the C3-H bond remains unaltered. A noticeable F KIE (F atom colored
red) and a secondary D KIE at C4 (D colored blue) should be however expected in
an E1 process.
If the two labeled positions of the substrates 4 and 6 are involved in different
steps of the mechanism, the deuteration at C3 slows down its own step but also
makes the subsequent steps slower, decreasing the observed size of the evaluated KIE. However, if the two isotopes are involved in the same step of the reaction the observed KIE can be enhanced (this step has become slower and thus
more rate-limiting) or alternatively shows no change (if the step was in fact ratelimiting).
6. The C4-secondary deuterium KIEs obtained from the double-isotopic fractionation method in substrates 3 and 4 were 1.009, 1.000 and 1.010, for formate,
acetate and imidazole, respectively.
The F KIE in substrates 5 and 6 was exclusively determined in presence of acetate
as base. The observed value was 1.0009.
D Di is sc cu us ss si io on n
Base-promoted E-eliminations can be E1, E2 and E1cB. In our case, the E1 mechanism would consist of the rate-limiting detachment of the fluorine leaving
group followed by a base-promoted fast proton-transfer step (equation A in
Scheme 37.2). In the E2 mechanism the bond breakage of the proton being transferred to the base and the detachment of the fluorine-leaving group are concerted
(equation B in Scheme 37.2). Finally, the E1cB mechanism consists of a proton
transfer step that leads to the formation of a carbanion intermediate, followed by
the departure of the leaving group (equation C in Scheme 37.2). Depending on the
rate-determining step of the reaction, we can distinguish between different types
of E1cB mechanisms. If the slow step is the formation of the carbanion intermediate (step 1 in equation C) the elimination is called (E1cB) irr . However, if the ratedetermining step of the reaction is the departure of the leaving group (step 2 on
equation C) the reaction is called (E1cB) R .
With the help of the kinetic isotope data we should be able to distinguish between the different options. Deuterium KIEs at C3 indicate the degree of bond
breakage of the C3-H bond, deuterium KIEs at C4 reflect the degree of rehybridization at the according position and the F KIEs are a measure of the breakage of
the C-F bond. All are obviously referred to the transition state of the slow step of
the reaction.
The experimental data in Table 37.1 indicate a primary deuterium KIE at C3 in
all cases studied. This result definitively rules out the E1 mechanism, as the
breakage of the C3-H bond does not occur during the rate-determining step. As we
can see in the E1 transition state represented in Fig. 37.2, the C-F bond is being
broken but the C3-H bond remains unaltered. A noticeable F KIE (F atom colored
red) and a secondary D KIE at C4 (D colored blue) should be however expected in
an E1 process.