Computer-Aided Design of Postpolymerization Modification Reaction Based on Aminolysis of α,α-Difluoroacetate Esters

Abstract

A new postpolymerization protocol based on the reactivity of α,α-difluoroacetate esters is proposed and rationalized via a combined effort of computational and experimental methods. Reaction systems designed on the basis of computational results are characterized in detail. It is found that aminolysis of polymers featuring α,α-difluoroacetate esters results in a 100% conversion of ester units to α,α-difluoroacetamide derivatives. This indicates that the new activated ester–amine chemistry reported here offers a promising approach to postpolymerization modifications.

Unveiling α-Etherification Effects on the Aminolysis of α,α-Difluoroacetate Enables the Aminolysis Post-polymerization Modification of α,α-Difluoro-α-(aryloxy)acetate-Containing Polymers

“…As such, calculations at the B3LYP/6-31G(d,p) level of theory resulted in an activation energy (energy difference between Init non_C and TS non_C ) of ΔE non_C = 33.9 kcal•mol −1 in the gas phase. In the same manner as the noncatalytic concerted mechanism for the already reported aminolysis reaction of α,α-difluoroacetates, 11 the PCM results (entries 2 and 3, Table 1) demonstrated that the solvation hardly affects the activation energy. Of note, the obtained ab initio results (entries 1, 4, and 5, Table 1) were in accord with the DLPNO-CCSD(T)/cc-pVTZ result (entry 6, Table 1), which is known to provide a high level of accuracy.…”

“… a The energies (Δ E ) are measured in kcal·mol –1 with respect to the reactant state (Init) in each mechanism. b The energy of TS2 with respect to the hemiaminal intermediate (IM) for the stepwise mechanisms is given in parentheses. c Reported in ref . …”

“…Recently, we developed new activated ester–amine chemistry employing α,α-difluoroacetates as feasible activated esters (Scheme ), which circumvents the disadvantages of activated esters commonly used in polymer science, such as N -hydroxysuccinimide, , pentafluorophenol, , and 4-nitrophenol, among others. , Specifically, using our approach, the atom efficiency increases during the aminolysis step, since a standard alcohol such as ethanol can serve as a leaving group. In addition, the post-polymerization modification reaction based on α,α-difluoroacetate aminolysis furnishes polymers featuring α,α-difluoroacetamide units in which the partially fluorinated moieties are preserved upon the installation of the amine functionality.…”

“…Recently, we developed new activated ester−amine chemistry employing α,α-difluoroacetates as feasible activated esters (Scheme 1), 11 which circumvents the disadvantages of activated esters commonly used in polymer science, such as N-hydroxysuccinimide, 12,13 pentafluorophenol, 14,15 and 4nitrophenol, 16 among others. 17,18 Specifically, using our approach, the atom efficiency increases during the aminolysis step, since a standard alcohol such as ethanol can serve as a leaving group.…”

Fast-Track Computational Access to Reaction Mechanisms Provides Comprehensive Insights into Aminolysis Postpolymerization Modification Reactions

“…Specifically, the reaction with nhexylamine afforded a 100% ester conversion in the postpolymerization step to provide the corresponding aminolyzed product. 21,22 As a proof of concept, we computationally analyzed this postpolymerization modification reaction using a realistic model structure consisting of a hexameric sequence (oligo-CF2CO2Et) and n-hexylamine as a reactant. We computed the four possible reaction pathways without further approximations such as ONIOM, 36 as depicted in Figures 6-9, and calculated the final reaction profiles at the DLPNO-CCSD(T) level of theory to gain an absolute insight into the reactivity.…”