Surmounting Byproduct Inhibition in an Intermolecular Catalytic Asymmetric Alkene Bromoesterification Reaction as Revealed by Kinetic Profiling

Abstract

Kinetic profiling has shown that a (DHQD) 2 PHALcatalyzed intermolecular asymmetric alkene bromoesterification reaction is inhibited by primary amides, imides, hydantoins, and secondary cyclic amides, which are byproducts of common stoichiometric bromenium ion sources. Two approaches to resolving the inhibition are presented, enabling the (DHQD) 2 PHAL loading to be dropped from 10 to 1 mol % while maintaining high bromoester conversions in 8 h or less. Iterative post-reaction recrystallizations enabled a homochiral bromonaphthoate ester to be synthesized using only 1 mol % (DHQD) 2 PHAL.

Auto-VTNA: An Automatic VTNA platform for Determination of Global Rate Equations

“…Following from this, auto-VTNA was applied to kinetic data from 22 publications, including stoichiometric and catalytic reactions (Table 4, entries 1-14) containing up to 6 reaction species (reactants, reagents, catalyst and additives). 5,8,9,34,[37][38][39][40][41][42][43][44][45][46] The current approach to VTNA experimentation involves performing a "standard" reaction, under synthetically relevant conditions, followed by "different excess" experiments, where only the initial concentration of each reaction species is altered.…”

“…This was performed for kinetic data obtained from 15 publications. 5,8,9,34,[37][38][39][40][41][42][43][44][45][47][48][49][50] Two of these publications were omitted as sequential VTNA had revealed that reaction orders change with the initial concentrations of reactants. 38,50 Kinetic data from the remaining 13 publications was re-analysed by Auto-VTNA sequentially (Table SX) and by automatic total VTNA (Table 2).…”