Aziridinium salts synthesis

Azacyclonol, 47 Azaphenothiazine, 429 Azepinamide, 137 Azetidone, synthesis, 419 Aziridinium salt, 79 Azlactone, 96 Azomycin, 238... 

A novel synthesis of relatively stable quaternary aziridinium salts has been introduced by Leonard854 Ternary iminlum perchlorates (obtained by treatment of the corresponding enamine with perohlorti acid) react with diazomethane to give the aziridinium perchlorate... 

Alkylation of aziridine in base gives the N-substituted aziridine as you might expect, but a second alkylation leads to a positively charged aziridinium salt that opens immediately to the useful bro-moamine. In this case, the product is an intermediate in the synthesis of two natural products, san-daverine and corgoine. 

Evans and Mitch( 101 elaborated this synthesis to afford a general approach to morphinans and to include a total synthesis of ( )-morphine (Scheme 3.7). The diastereomerically pure aziridinium salt, 43, was prepared as illustrated and converted to the aldehyde (44) in 95% yield simply by dissolving in anhydrous DMSO at ambient temperature (Kornblum oxidation). Lewis acid catalyzed ring closure occurred in high yield (80%) to the isomorphinan-10-ol... 

This synthesis involves a ring-opening reaction of the aziridinium salts as the key step and provides a novel route to 2-alkylisoquinolines. 

A formal total synthesis of ( )-morphine has been achieved by adopting the above synthetic route (Scheme 18). The tetrahydropyridine 91, prepared from the reaction of A/ -methyl-4-piperidone with 2,3-dimethoxy-phenyllithium, followed by dehydration, was converted to the bicyclic en-amine 92 by treatment with the ylic dibromide. Kinetic protonation of 92 with perchloric acid gave the trans-fused immonium salt, which upon dissolution in methanol equilibrated to the thermodynamically prefered cis isomer 93. Treatment of 93 with diazomethane brought about the formation of the aziridinium salt 94, which was readily transformed into the a-amino aldehyde 95 by its oxidation with dimethyl sulfoxide. It is also worth noting that the Komblum oxidation of aziridinium salts leads to the construction of a-amino aldehydes efficiently. Lewis-acid-catalyzed cyclization of 95 afforded the morphinan carbinol 96 in 80% yield. Successive mesylation and reduction of the mesylate derived from 96 with LiBEtjH afforded morphinan (97) in excellent yield. In this instance, direct conversion of 93 to 97 by treatment with diazomethane gave approximately 1 % of the desired product. Lemieux-Johnson oxidation of 97 under acidic conditions furnished the ketone 98, which was previously transformed into ( )-morphine by Gates. In order to confirm the structure of 98, its conversion to the known... 

C-14 epimer 100 via base-catalyzed equilibration and subsequent reduction of the a,/ -unsaturated ketone 9 was also carried out. Thus the formal total synthesis of ( )-morphine has been accomplished by employing the oxidation of the aziridinium salt as a key step. 

A total synthesis of ( )-codeine also utilized the aziridinium salt 94 as a key intermediate, which was converted to 100 via epidihydrothebainone methyl ether (98) according to Evans s procedure. Specific ether cleavage reaction of 100 with NaSEt afforded dihy othebainone (101) in 100% yield. Since dihydrothebainone (101) had already been transformed into codeine (102), this synthesis constitutes a formal synthesis of 102 (Scheme 19). 

The synthesis of tryptamines by Mannich reactions involves the aziridinium salt as an intermediate. For instance, the reaction of indole (143) with chloroacetaldehyde (148) in the presence of a secondary amine afforded... 

A simple and versatile method for the synthesis of aziridinium salts involves the reaction of a diazoalkane with an iminium salt (82TL285, B-83MI 102-01). The aziridinium salt thus formed was oxidized to an aminoaldehyde by DMSO (Scheme 39). A key step in the preparation of the oxindole alkaloid gelsemine (104) involves the carbonylation of the unsaturated aziridinium ion (103) with disodiumtetracarbonyl picrate-dioxane complex under a CO atmosphere followed by base-promoted epimerization and deprotonation (Scheme 40) <92JOC1035>. 

A new 4-arylisoquinoline alkaloid, latifine, isolated from Crinum latifolium, has been identified as an isomer (21, R = OH, R =H) of cherylline (21, R =H, R =0H) (S. Kobayashi, T. Tokomuto and Z. Taira, Chem.Comm., 1984, 1043). A novel synthesis of cherylline has been achieved from the iminium salt (19) by treatment with diazomethane, cyclisation of the resulting aziridinium salt (20) and hydrogenolytic removal of the benzyl groups (T. Kametani, et al., J.chem.Soc., Perkin I, 1982, 2935. 

Aminomercuration leads to substituted organomercurials 5.5, which also suffer demercuration with sodium borohydride, preferentially under PTC conditions [BEl, EB4] (Figure 5.5). The mechanism proposed for this reduction in protic solvents is an ionic one, implying the intermediate formation of aziridinium salt [L3]. This method has been applied to the synthesis of cyclic amines from a,P-ethyienic precursors 5.6 [EB4] (Figure 5.5). When the reduction in run in alcohol or water, mixtures of five- and six-membered cyclic amines are obtained from each precursor 5.6 (n = 1 or 2). 

Duriska, M.B., Grondin, J., Servant, L., Birot, M. and Deleuze, H., Synthesis and characterization of novel ionic liquids iV-Substimted aziridinium salts, J. Heterocycl. Chem. 49 (3), 652-657 (2012). 

The bicyclic azetidinium salts 67 were formed by intramolecular ring closure of 5-mesylates 66, even when competitive aziridinium salt formation could have occurred (Scheme 20). The pyrrolidinium salts 68 were obtained similarly. Compounds 67 and 68, with X=F or OMs, were isolable solids. Synthesis of amino-fluoro-sugar derivatives from Al-tosyl-aziridine derivatives is covered in Chapter 8 and 19. 

Figure 8.8 Synthesis of [2,3- C2lpiperidines and [ C2]aziridinium salts from [ C2letbylene oxide...

Additions to Electron-Deficient Species. Diazomethane will also add to highly electrophilic species such as sulfenes or im-minium salts to give the corresponding three-membered ring heterocycles. When the reaction is performed on sulfenes, the products are episulfones which are intermediates in the Ramberg-Backlund rearrangement, and are therefore precursors for the synthesis of alkenes via chelotropic extrusion of S02- The sulfenes are typically prepared in situ by treatment of a sulfonyl chloride with a mild base, such as Triethylamine (eq 47). Similarly, the addition of diazomethane to imminium salts has been used to methyle-nate carbonyls. In this case, the intermediate aziridinium salt is treated with a strong base, such as n-Butyllithium, in order to induce elimination (eq 48). 

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