Ammonium-Directed Olefinic Epoxidation: Kinetic and Mechanistic Insights

Abstract

The ammonium-directed olefinic epoxidations of a range of differentially N-substituted cyclic allylic and homoallylic amines (derived from cyclopentene, cyclohexene, and cycloheptene) have been investigated, and the reaction kinetics have been analyzed. The results of these studies suggest that both the ring size and the identity of the substituents on nitrogen are important in determining both the overall rate and the stereochemical outcome of the epoxidation reaction. In general, secondary amines or tertiary amines with nonsterically demanding substituents on nitrogen are superior to tertiary amines with sterically demanding substituents on nitrogen in their ability to promote the oxidation reaction. Furthermore, in all cases examined, the ability of the (in situ formed) ammonium substituent to direct the stereochemical course of the epoxidation reaction is either comparable or superior to that of the analogous hydroxyl substituent. Much slower rates of ring-opening of the intermediate epoxides are observed in cyclopentene-derived and cycloheptene-derived allylic amines as compared with their cyclohexene-derived allylic and homoallylic amine counterparts, allowing for isolation of these intermediates in both of the former cases.

Epoxide ring-opening approach to the synthesis of diverse trisubstituted cyclopentanes

“…15 Pyridine derivatives are found to have a large spectrum of biological activities, 16 therefore, pyridin-3-ol (3-PyOH) was chosen as an O-nucleophile. It was established experimentally that cesium carbonate can be used as a catalyst for the ring-oprning reactions of 3-substituted carbocyclic epoxides instead of sodium hydride, the common reagent for the epoxide cleavage with phenols.…”

“…All reagents and solvents were purchased from commercial sources and used without further purification. Starting epoxides 1 and 2 previously described in the literature 15 were characterized by comparing their 1 H NMR spectra to the published data. All yields reported in this publication refer to isolated ones of compounds and their purity was determined by 1 H NMR.…”

Base‐Catalyzed Intramolecular Hydroamination of Cyclohexa‐2,5‐dienes: Insights into the Mechanism through DFT Calculations and Application to the Total Synthesis of epi‐Elwesine

“…Similarly, model compound 2 d led to the corresponding epoxide 28 b with the same stereoselectivity. The high syn ‐stereocontrol could arise either through a directed epoxidation from the corresponding ammonium42 or from the N‐oxide formed in situ (Scheme ) 43. The latter would be formed by oxidation of the amine before epoxidation and then reduction with Na 2 S 2 O 5 , thus regenerating the tertiary amine.…”

Regio- and stereoselective synthesis of new diaminocyclopentanols

“…Epoxides 3a,b (Scheme 1) were obtained by the addition of benzyl(methyl)amine or dibenzylamine to cyclopent-2-en-1-yl acetate ( 1 ) followed by epoxidation [28]. Epoxides 6a,b were synthesized from 3a,b through epoxide ring inversion using glacial acetic acid as the oxirane-cleaving agent [29].…”

“…Epoxides 3 and 6 were identified by 1 H NMR data [28]. Morpholine ( 7a ), 2-methyl-1 H -imidazole ( 7b ), N -acetylpiperazine ( 7c ) and 9 H -purin-6-amine ( 7d ) were used as nucleophiles (Fig.…”