Aziridinium ions, reduction

Although geneologically related to indoles, the dihydroindoles behave chemically rather like alkyl anilines. When diphenylamine reacts with chloro-propionyl chloride, amide 40 results this in turn readily cyclizes to oxindole 41. Sodium hydride followed by 2-chloroethyldimethylamine alkylates the 3-position (possibly through an intermediate aziridinium ion) partial demethylation is accomplished by refluxing with ethylchiorocarbonate, followed by hydrolysis of the intermediate carbamate to give indolinone 42, the antidepressant amedalin Repetition of this sequence on the chloropropyl homologue, followed by reduction of the appropriate indolinone produces dihydroindole 43, daledalin, which also has antidepressant activity. ... 

The l-benzazepin-2-one system continues to be a target for synthesis because of the pharmacological activities of compounds with this skeletal unit. In this context, a ring-enlargement route to 337 on treatment of 336 with silver nitrate has been reported (Scheme 45). This reaction presumably proceeds via an aziridinium ion intermediate. The structure of the product was confirmed by reduction of 337 to 338. The possible isomeric product 339 was made separately and shown to be different <2002SL1350>. 

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. 

Treatment of 2,3 Cpoxy-l-amines with Lewis acid induces a rearrangement to aziridinium ions that react efficiently with a nucleophiles to give functionalized hydroxy sulfides or hydroxy amines (Equation 23) <1997SL11>. Under the influence of ethylaluminium chloride, an epoxide tethered to an azide undergoes Lewis acid-assisted cyclization followed by an intramolecular Schmidt reaction and subsequent in situ reduction of the intermediate iminium species upon addition of sodium borohydride (Scheme 8). This protocol was used as a key step in a novel synthesis of indolizidine alkaloids of pharmaceutical interest <20030L583, 2004JOC3093>. 

Treatment of some mesylated N,N-diallylamino sugars with triethylamine tnhydrofluoride results in the fluorination and regioselective transfer of the nitro gen atom to give, after platinum-catalyzed reductive deallylation, 2,3-amino-fluorodeoxysugars A mechanism involving aziridinium ions has been proposed [44] (equation 32)... 

Ring expansion reactions of 2-substituted pyrrolidines, with the intermediacy of a bicyclic aziridinium ion, has provided new piperidines. Treatment of the chiral olefmic imine 264 with Br2, followed by reduction of the resultant ion 265 results in the formation of a separable mixture of spiromethylpyrrolidines and a single spiropiperidine 266 (23% yield), a precursor of (-)-nitramine 267 (Scheme 80) <05SL1726>. 

Another proposition envisages involvement of one molecule of cinnamic acid, a molecule each of benzoylacetic acid and an appropriately substituted spermidine rather than spermidine itself. Elimination of the spermidine substituent (possibly involving the aziridinium ion) is followed by an attack from the carbanion derived from benzoylacetic acid with the formation of a new C-C bond. The other reactions involved in the biogenesis are of well-established nature viz, Michael addition, carbonyl reduction and amide formation. The carbonyl reduction step (and possibly even the cyclization to the y -lactam) necessarily follows the C-C bond formation and the generation of the other C-N bonds may either precede or succeed the above step (Scheme 10). 

The synthesis of 2-acetamido-1,6-anhydro-2,3-dideoxy-B-D-rlbo-hexopyranose from a 3-thlo-sugar by reductive desulphurization is covered in Chapter 9. Reduction (NaBH ) of secondary mesylates with a vicinally related trans-dlallylamlno group proceeds to give deoxygenated products via aziridinium ion intermediates, sequence, sometimes the product is that of amino migration examples are detailed in Chapter 9. 

In the case of the olefin (481), the n.m.r. spectrum of the mercurial shows it to be exclusively one of the two possible astereoisomers (482). Although a complexing of mercury by nitrogen could be envisaged, leading to cis addition, in fact the reaction proceeds by a formal trans addition of mercury and nitrogen across the double bond, as is shown by detailed examination of the n.m.r. spectra of products from and /roftJ-substituted amino-olefins. Reduction of (482) with sodium borohydride yielded a mixture of (483) and (484), for which an intermediate aziridinium ion is responsible. 

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