Desymmetrization and Kinetic Resolution of Endoperoxides Using a Bifunctional Organocatalyst

Abstract

Bifunctional thiourea/amine organocatalysts have been used for the desymmetrization of meso-endoperoxides using the Kornblum−DeLaMare reaction, giving 4-hydroxyketones in 78−98% yields with ≤98:2 enantioselectivity. The influence of the catalyst structure, solvent, and temperature was examined. The most promising catalyst was applied to the kinetic resolution of racemic endoperoxides to give enantioenriched materials (≤99:1 er).

Practical and scalable enantioselective synthesis of (+)-majoranolide from Cyrene

“…The alkylidenes were unreactive with peracetic acid, and starting material remained after 48 hours (data not shown). We have previously had success increasing the reactivity of ketones in the Baeyer–Villiger reaction using the combination of PTSA and m -CPBA, 20,27 which is followed by an aqueous HCl treatment to hydrolyse residual formate ester, which is also formed in the reaction. 25,28 Applying these conditions to 15 and 17 gave complete consumption of the starting material after only 2 hours and a good yield of lactones 19 and 20 were obtained (Table 3, entries 1 and 2).…”

The Kornblum DeLaMare rearrangement in natural product synthesis: 25 years of innovation

“…Recently, Greatrex and co-workers divulged an innovative thiourea/amine organocatalytic system to desymmetrise meso -endoperoxide of the type shown in Scheme 5. 46 Key to the success of this transformation is the steric requirement of the catalyst, particularly size of the dialkylamine at C1 (cat. 38 ).…”