title: Synthesis and purification of iodoaziridines involving quantitative selection of the optimal stationary phase for chromatography.
abstract: The highly diastereoselective preparation of cis-N-Ts-iodoaziridines through reaction of diiodomethyllithium with N-Ts aldimines is described. Diiodomethyllithium is prepared by the deprotonation of diiodomethane with LiHMDS, in a THF/diethyl ether mixture, at -78 °C in the dark. These conditions are essential for the stability of the LiCHI2 reagent generated. The subsequent dropwise addition of N-Ts aldimines to the preformed diiodomethyllithium solution affords an amino-diiodide intermediate, which is not isolated. Rapid warming of the reaction mixture to 0 °C promotes cyclization to afford iodoaziridines with exclusive cis-diastereoselectivity. The addition and cyclization stages of the reaction are mediated in one reaction flask by careful temperature control. Due to the sensitivity of the iodoaziridines to purification, assessment of suitable methods of purification is required. A protocol to assess the stability of sensitive compounds to stationary phases for column chromatography is described. This method is suitable to apply to new iodoaziridines, or other potentially sensitive novel compounds. Consequently this method may find application in range of synthetic projects. The procedure involves firstly the assessment of the reaction yield, prior to purification, by (1)H NMR spectroscopy with comparison to an internal standard. Portions of impure product mixture are then exposed to slurries of various stationary phases appropriate for chromatography, in a solvent system suitable as the eluent in flash chromatography. After stirring for 30 min to mimic chromatography, followed by filtering, the samples are analyzed by (1)H NMR spectroscopy. Calculated yields for each stationary phase are then compared to that initially obtained from the crude reaction mixture. The results obtained provide a quantitative assessment of the stability of the compound to the different stationary phases; hence the optimal can be selected. The choice of basic alumina, modified to activity IV, as a suitable stationary phase has allowed isolation of certain iodoaziridines in excellent yield and purity.
authors.affiliation: Department of Chemistry, Imperial College London.
authors.forename: Tom
authors.initials: T
authors.lastname: Boultwood
authors.affiliation: Department of Chemistry, Imperial College London.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Affron
authors.affiliation: Department of Chemistry, Imperial College London; j.bull@imperial.ac.uk.
authors.forename: James A
authors.initials: JA
authors.lastname: Bull
mesh_terms: D001388:Aziridines / Q000302:isolation & purification*; D002845:Chromatography / Q000379:methods*; D006847:Hydrocarbons, Iodinated / Q000302:isolation & purification
chemical_list: D001388:Aziridines; D006847:Hydrocarbons, Iodinated