Immonium ions, reduction

The reduction in the selectivity of forming C2HgN+ as the alkyl chain length is increased reflects the enhanced rate of hydrogen exchange processes which allow a deuterium atom to be transferred to a position in which it is incorporated in the immonium ion. 

A common mechanistic interpretation involves hydride transfer in the reduction of the immonium ion intermediate ... 

Sodium borohydride reacts selectively at the immonium moiety7-9 in the azolium salts reduction occurs depending on the substitution pattern and the formation of the immonium ion system.5... 

Rosazza et al. (52) have proposed the mechanism shown in Fig. 6 for the formation of both dihydrovindoline ether and its dimer from vindoline. This mechanism, which proposes an intermediate enamine-immonium ion species 54-55 produced by N-oxidation, followed by intramolecular attack of the C-l 6 hydroxyl oxygen, also accounts for the formation of 3-acetonyldihydro-vindoline ether 42 from vindoline by Streptomyces albogriseolus (49). Reduction of the immonium ion 55 thus leads directly to dihydrovindoline ether, whereas its capture by acetoacetate or the enamine 54 (79) leads to 42 and 45, respectively. 

Reaction of the immonium ion (157) with dihydrogen sulfide produces the l,3-dithiole-2-thione (158) while reduction of the ion (157) with sodium borohydride, followed by treatment with sulfuric acid, resulted in the formation of the 1,3-dithiolylium salt (48) (76S489). 

The first total synthesis of cinchonamine (277) and 2-epicinchonamine (278) proceeds via the epimers (279), which were prepared by two independent methods.169 Scheme 28 illustrates the more efficient of the two syntheses, which involves as its first stage the condensation of 2-lithio-iV-benzenesulphonyl-indole with N-benzoylmeroquinene aldehyde (280), itself obtained by reduction of the readily available JV-benzoylmeroquinene ester (281). The critical cyclization stage [(279)— (283)+ (284)] that occurs on prolonged heating at 155 °C presumably proceeds via the immonium ion (282), since separation of the epimers of (279) followed by dehydration and cyclization affords the same mixture of (283) and (284). Finally, the hydroxyethyl group was introduced by the reaction of the Grignard derivatives of (283) and (284) with ethylene oxide.169... 

This modification resulted in a yield improvement for the pentacyclization process from 47 % to 66 %. Treatment of the amino ether 192 with diisobutylaluminum hydride in refluxing toluene accomplished Eschenmoser-Grob fragmentation and reduction of the initially formed immonium ion, to give the unsaturated amino alcohol 193 in 86% yield. It was gratifying to find that 193 was the only product formed in this reaction. In the tetrahydropyran derivative, reduction of 192 to 193 is accompanied by about 15 % simple elimination. Displacement of the tosyl group in 196 gives sulfide 197, which is oxidized to sulfone 198. This material is metallated and coupled with enantiomerically pure aldehyde to secure the codaphniphylline skelton [74]. 

Triazolium salts (335) are not readily reduced by NBH. Indeed, 4-phenyl- and 4,5-diphenyl-1,3-dimethyl-1,2,3-triazolium iodides do not undergo reduction, yet l-methyl-2-phenyl-l,2,3-triazolium triflate (336) is reduced to the 4-triazoline 337. This reactivity pattern is explained by the need for an immonium ion for successful reaction. The presence of a C-2 substituent in 336 makes this possible the lack of such a substituent localizes the double bond joining C-4 and C-5. 

A new, stereospecific synthesis of (+)-isoretronecanol, by a transannular route, has been developed by Leonard et al. Dieckmann cyclisation of NN-bis-(y-ethoxycarbonylpropyl)benzylamine gave ethyl l-benzyl-5-oxo-l-azacyclo-octane-4-carboxylate (20), whose perchlorate was shown to possess a bicyclic structure. Hydrogenation of this perchlorate in ethanol, using palladised charcoal catalyst, afforded ethyl ( )-isoretronecanolate perchlorate (22) as sole product, presumably by stereospecific addition of hydrogen at the less hindered face of the intermediate debenzylated immonium ion (21). Reduction of the free base corresponding to (22), by means of lithium aluminium hydride, gave (+ )-isoretronecanol (23), the stereochemical purity of which was shown by g.l.c. analysis to be >98%. 

Synthetic work in this area includes a new, stereospecific synthesis of sparteine and a synthesis of isosophoramine. The reduction of quinolizidone (16) by means of lithium aluminium hydride affords, as noted previously, a dimeric product (17), presumably via condensation of the initially formed enamine (18) with the corresponding immonium cation (19). With di-isobutyl aluminium hydride the yield of (17) can be increased to 85%. Analogous reduction of the dilactam (20), prepared by base-catalysed condensation of the bromo-lactam (21) with a-piperidone, gave an intermediate (22), in which the enamine and immonium ion units are present within the same molecule. Intramolecular cyclization of (22), via a transition state derived from the conformation (23), spontaneously gave the... 

In contrast to the reductive cyclization, the indolo[2,3-a]quinolizidine structure can also be formed from 7V-)8-(3-indolyl)ethylpiperidine derivatives by oxidizing the piperidine moiety to an immonium ion followed by spontaneous cyclization. Unfortunately, chemical yields obtained from this oxidative cyclization tactic were extremely low in most cases <62JOC2283, 62JA4914). An alternative was to form the piperidine A-oxide and then to cyclize it into indolo[2,3-a]quinolizidine using trifluoroacetic anhydride <72CC930> or ferrous sulfate <72JOC1083>. 

In connection with partial synthesis in the ring-E-seco alkaloids and the heteroyohimbine group, several Nb-oxides have been prepared. Dihydrocory-nantheine, on oxidation with m-chloroperbenzoic acid, affords two epimeric Nb-oxides whereas its pseudo isomer, hirsutine, gives only one. Desmethyl-hirsuteine Nb-oxide (91), when treated with trifluoroacetic anhydride in methylene chloride, undergoes the Polonovski reaction reduction of the product by means of buffered sodium cyanoborohydride then affords a mixture of desmethylcorynantheine (92), 3-i5o-rauniticine (93), and akuammigine (94) (Scheme 12). Clearly, formation of an immonium ion can occur in the Polonovski reaction either towards C-3 [- (95)], which results in the ultimate epimeriza-... 

Evidence for the intermediacy of the enamine (138) and the immonium ion (140) derives from the condensation reaction in which potassium cyanide replaced sodium cyanoborohydride the immonium ion (140) was thus trapped by reaction with nucleophilic cyanide ion, with formation of 21-cyanotetrahydroalstonine (141a) and 21-cyanoakuammigine (141b). Both cyano-compounds suffered slow reduction to the parent alkaloid by sodium borohydride, and were re-converted (by silver acetate) into the precursor immonium ions (140), which could be rapidly reduced (NaBH4) to the alkaloids. Scheme 17 illustrates some, but not by any means all, of the numerous interconversions involved in these biomimetic experiments. 

The reduction of C=N bonds and immonium ions was suggested to be involved in the TV-alkylation of amines by CO + H2O with different rhodium catalysts like RhCU, [Rh(COD)Cl]2, RhCl(PPh3)3, and... 

The 2H- and 3//-pyrrolium cations are essentially immonium ions and as such are electrophilic they play the key role in polymerisation (section 13.1.8) and reduction (section 13.8) of pyrroles in acid. In the reaction of pyrroles with hydroxylamine hydrochloride, which produces a ring-opened 1,4-dioxime, it is probably the more reactive 3//-pyrrolium cation which is the starter. Primary amines, RNH2, can thus be protected, by conversion into l-R-2,5-dimethylpyrroles (section 13.18.1.1), the protecting group being removable by this reaction with hydroxylamine. ... 

Ayer et al. proposed the pathway for the biogenesis of macleanine (68) (47). Most of the Lycopodium alkaloids known to date possess functionality at C-5. Fawcettimine (93) readily forms a transannular carbinolamine 93a. Macleanine (68) might be derived from fawcettimine (93) through reductive amination to generate 94, formation of the internal immonium ion 95, and subsequent transannular cycUzation (47). 

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