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