3.2 Reaction B
In Li group’s experiment, with the participant of additive NaOAc, the
product would reverse to be iminolactone P2 in 1,4-dioxane
solvent. As shown in Figure 4, OAc-, generated from
the excess ionic compound NaOAc, could coordinate to 9 to
create a more stable intermediate 12 in comparison to10 (the corresponding free energy diagram from 9 to11 in 1,4-dioxane is given in Figure S4 in Supporting
Information) through the transition state TS9 with the barrier
of 6.2 kcal/mol. 12 would then isomerize toη 3intermediate 13 , followed
by the C–N reductive elimination (TS10 ) to yield product
complex 14 . As shown in Figure 4, 9 could also
transform into a more stable O-coordinated intermediate 15 via
the C–C rotation and OAc- coordination steps,
respectively. The subsequent C–O
reductive elimination transition state (TS12 ) is 2.4 kcal/mol
lower than the C–N one (TS10 ), suggesting the
iminolactone complex 17is the major product. Other infeasible pathway is put into Figure S5 in
Supporting Information.
FIGURE 4 Free energy profiles from 9 to product
complex 17 in reaction B. The relative free energies and
relative enthalpic energies (in parentheses) are given in kcal/mol
The pathway of OAc- coordinating to R1 at the
entrance of reaction B was also considered, but the high barrier for the
C–H bond activation (see TS2’ and TS2” as shown in
Figure S6 in Supporting Information) precludes this possibility.
As shown in Figure 4, the regioselectivity-determining step in reaction
B is the reductive elimination. The relative stability of reductive
elimination transition state (TS10 and TS12 ) controls
the regioselectivity. To gain insight into origin of the observed
regioselectivity, natural population analysis (NPA) was performed.
Figure 5 gives the NPA charges on the atoms of C…N and C…O
which participate the reductive elimination. Due to the stronger
electronegativity of O atom in comparison to N atom, the charge on the O
atom (-0.508 e ) in TS12 is more negative than that on
the N atom (-0.263 e ) in TS10 . Thus, the positive C1
atom (0.154 and 0.182 e in TS10 and TS12 ,
respectively) prefers to interact with O atom to carry the C–O
reductive elimination to afford iminolactone product. Moreover, the
steric effect could also account for the O-coordinated regioselectivity.
As indicated in Figure 5, the distance between carbonyl carbon atom and
C1 atom in TS10 (2.47 Å) is shorter than that (2.82 Å) inTS12 , causing much larger steric repulsion and destabilizingTS10 .
FIGURE 5 The optimized structures of TS10 andTS12 . NPA charges are given in e and distances are given
in Å