Aziridinium ions ring opening

Aziridinium ion-based click chemistry provides convenient access to pyrazolo[l,2-ajpyrazoles, active inhibitors of penicillin-binding proteins [58, 59]. Ring-opening of aziridinium ions 32 at the benzylic position with hydrazine, followed by intramolecular cyclization, gave pyrazolidin-3-ones 37 in excellent yields (Scheme 12.27). Heating of the hydrazides 37 with aromatic aldehydes at reflux in absolute... 

Scheme 1.30. Cationic cyclization/aziridinium ion formation/nucleophilic ring-opening procedure for the synthesis of pyrrolidines.

Furthermore, triethylamine trisfhydrogen fluoride) is a highly versatile and easy-to-handle source of fluoride ions. Therefore, its use can be highly recommended for the ring-opening hydrofluorination of aziridines156 (or aziridinium ions166) see also refs 97 and 167. 

Isomerization of the enantiopure hydroxylated azepane 42, after hydroxyl group activation, afforded either the ring-contracted piperidine derivative 45 (on O-mesylation to 43 followed by internal displacement to the aziridinium ion intermediate 44 and subsequent chloride ion induced ring opening) or the chiral ethylene-bridged morpholines 48 via 47 and an intramolecular Mitsunobu reaction of 46 (Scheme 4) <1996TL1613>. 

Several studies on the reactions and preparation of aziridines have been published. The ring opening of 2-substituted aziridines, accomplished by first converting them into aziridinium salts by reaction with a benzyl bromide and then attack of the bromide counter ion, gave only one bromide in a regio- and stereo-specific reaction.43 Since attack by the bromide ion of the aziridinium salt only occurred at the most substituted carbon with an inversion of stereochemistry, it was concluded the reaction occurred by an SN2 mechanism. This was supported by calculations at the MPWBlK/6-31+G(d) level of theory for reactions featuring two solvating acetonitrile molecules embedded in an acetonitrile matrix. 

The transition states for the ring opening reaction of an aziridinium ion by chloride ion were calculated using the IRC and QRC methods.56 Whereas the IRC method found only one transition state for the reaction, the QRC method suggested that there were two transition states that occurred sequentially along the reaction coordinate without an intervening intermediate. 

An organometallic reagent has also been used to ring-open an aziridinium ion (181), formed in situ by the treatment of the amino alcohol derivative 180 with lithium chloride. Subsequent addition of the aryl magnesium bromide 182 led to the formation of amine 183 in 95% overall yield <02TL6121>. 

C to —10°C) followed by a Dess-Martin oxidation provided the necessary azidoaldehyde. An intramolecular Staudinger cyclization followed by reduction of the resultant amine provided azepine 364. Treatment of 364 with iodine induced an interesting double cyclization. Initial iodination of the double bond is followed by aziridinium ion formation 365. An intramolecular and stereospecific ring opening by the carboxylate provides the target (—)-stemospironine. 

The direct synthesis of the morphinan skeleton (107) from (105) involves the intramolecular ring opening by the enolate anion of the in situ generated aziridine cation (106) (Scheme 41) <88J0C2144>. Compound (108) was found to rearrange thermally to the thermodynamically favored azabicyclo-[3.3.1]octane (110) via the aziridinium ion (109) (Scheme 42) <93CC758>. 

Closure of 5-halo-amines by nucleophilic displacements of halogen, is complemented by the conversion of iV-chloro-pent-4-enylamines into 3-chloropiperidines by exposure to tetra-n-butylammonium iodide. The process is believed to involve conversion to an A -iodo-amine, which serves as an electrophilic source of iodine, cyclisation to a 2-(iodomethyl)-pyrrolidine, ring closure to a bicyclic aziridinium ion and ring opening via attack by chloride to produce the six-membered heterocycle. 

Deprotonation to the enamine anion, selective coupling with the allylic terminus of dibromide 114, followed by an intramolecular enamine alkylation, afforded reduced isoquinoline 119. A rather elegant conversion to aminoaldehyde 122 ensued. Immonium ion formation in 119 via protonation with perchloric acid at first yielded the kinetic trans isomer, which underwent equilibration upon reflux in methanol to give the corresponding crystalline cis product 120. Diazomethane treatment led to aziridinium salt 121, which upon exposure to DMSO, ring opened with concomitant oxidation in a Komblum fashion to the aldehyde 122.63 Treatment with Lewis acid effected B-ring closure, thus... 

---