Iminium salts, reaction with

The previous sections have dealt with stable C=N-I- functionality in aromatic rings as simple salts. Another class of iminium salt reactions can be found where the iminium salt is only an intermediate. The purpose of this section is to point out these reactions even though they do not show any striking differences in their reactivity from stable iminium salts. Such intermediates arise from a-chloroamines (133-135), isomerization of oxazolidines (136), reduction of a-aminoketones by the Clemmensen method (137-139), reductive alkylation by the Leuckart-Wallach (140-141) or Clarke-Eschweiler reaction (142), mercuric acetate oxidation of amines (46,93), and in reactions such as ketene with enamines (143). 

The key intermediate 21 is in principle accessible in any of several ways. Thus reaction of thiophenecarbox-aldehyde with amninoacetal would lead to the Schiff base treatment with acid would result in formation of the fused thiophene-pyridine ring (21). Alkylation of that intermediate with benzyl chloride gives the corresponding ternary iminium salt. Treatment with sodium borohydride leads to reduction of the quinolinium ring and thus formation of ticlopidine (24). ... 

However, under our conditions20,35,37 as well as a variety of other conditions,53,54 the formal [3 + 3] cycloaddition reaction of the iminium salt 51 with pyrone 12 failed to provide any desired pentacycle 52. This failure prompted us to think that 51 might be sterically too demanding, thereby obstructing the reaction pathway. 

Reversibility of 67t-Electron Electrocyclic Ring-Closure. The high diastereoselectivity obtained in these reactions here is likely a result of the reversible 67t-electron electrocyclic ring-closure.20,37 41 The best evidence for the reversibility of this ring-closure is described in Scheme 12. We were able to isolate both the desired major isomer 10 and the minor isomer 44 from the formal cycloaddition reaction of the iminium salt 56 with pyrone 12. 

The same methodology was employed by Tiecco to effect the cyclizations of 0-allyl oximes 164 indicated in Scheme 25. Treatment of the intermediate iminium salt 165 with sodium borohydride affords M-alkyl isoxazolidines 166 [95]. Alternatively, 165 can be treated with water to produce M-unsubstituted isoxazolidines 167 [96]. This synthesis of M-alkyl isoxazolidines represents a valid alternative to that described in Scheme 23. Moreover, the present cyclization reaction is much more stereoselective than the cyclization of 0-allyl hydro-xylamines. In fact, when the methyl derivative 168 was employed, the two isomeric isoxazolidines 153 and 154 were obtained in a ratio of 95 5. The same two products were, in contrast, formed in a 1 1 ratio when the reaction was carried out starting from the corresponding 0-allyl hydroxylamines. Clearly, the steric requirements for the selenium-induced cyclization of the 0-allyl oximes are much greater than those for the corresponding 0-allyl hydroxylamines. 

Few reactions of alkynes with C—X bonds are valuable for the preparation of four-membered hetero-cycles. Ynatnines react with aldehydes and ketones in the presence of Lewis acids to give unstable oxetene derivatives which undergo electrocyclic opening (Scheme 43). Open-chain products are also obtained with thiocarbonyl compounds,Schiff bases and iminium salts. Reactions of ynamines with carbon dioxide, ketenes, - ketenimines and isocyanates " often give mixtures of products and are of little preparative value. 

Treatment of the phosphino-iminium salts (169) with potassium hydroxide in THF affords the formylphosphines (170), which are remarkably stable in solution compared with the related phosphine oxides Phosphines bearing aminoyl radical substituents, e.g. (171), have also been prepared. The phospha[3]triangulane, (172), has been obtained from the reaction of bicyclo-propylidene with a metal complexed phenylphosphinidene. " The phosphino-trithiacyclophane (173) has been prepared by the base-promoted reaction of... 

Addition Reactions.- The photoelectron transfer process of the iminium salt (38) with the 3-butenoate anion results in the formation of the allylated product (39). The reaction involves decarboxylation of the 3-butenoate followed by a radical coupling reaction. The photoaddition of halogenated alkenes to the tetraraza phenanthrene (40) yields products (41) of (2+2)-addition. The Eu(III)/Eu(II) photoredox system has been studied with regards to its reactivity toweu ds a-methylstyrene. Irradiation of the system at > 280 nm in methanol yielded the products (42) and(43). ... 

A similar mechanism is thought to be involved in the formation of a-trilluoromethyl ketone 7 instead of expected amine 6 during the reaction of iminium salt 5 with CF3Br under Barbier conditions (equation 4) . It was proposed that pyridine probably transforms iminium ion 5 into the enamine (l-pyrrolidino)-l-cyclohexene by elimination of HQ, which then undergoes a radical chain reaction with CF Br as shown in Scheme 1 to give 7. This is supported by the observation that no condensation products are observed when iminium salts lacking removable a-hydrogens are used. 

In a regiochemical investigation of the reaction of iminium salt (32) with a series of unsymmetrical methyl ketones, Jasor et al. have observed that the site of aminomethylation is solvent dependent (equation 7, Table S). It is found that in MeCN, reaction occurs exclusively at the least-substimted position, while in TFA it occurs mainly at the most-substituted position. Yields are good (70-90%) in TFA but are somewhat reduced in MeCN due to dialkylation, which can be overcome if the more bulky NA -diisopro-pyliminium salt is used. How the solvent influences the two possible rate-determining steps, enolization versus aminomethylation, and the extent of reversibility of the reaction need further investigation in order to determine the basis for the observed dichotomy in regiochemistry. 

Electron-rich oxygenated dienes react readily with iminium salts and with imines under Lewis acid catalysis.49-51 Some examples are shown in Table 2-VI. In all cases, only one regioisomer was detected in the reaction, and in every instance product structure is in agreement with predictions based on Scheme 2-1. 

Amides are converted to iminium salts 98 with oxaly chloride. Selenolysis of 98 with the reagent 99 generated from lithium aluminum hydride and elemental selenium will give selenoamides (Eq. 35) [66]. The reaction is effective... 

Ynamines (27) are formed in the reaction of di-iminium salts (28) with t-butoxide anion or triethylamine. ... 

The simplest stable singlet carbene derived from a cyclic precursor is cyclo-propylidene. Like other carbocyclic carbenes, it does not contain a heteroatom within the ring and is therefore not further discussed here. The first cyclic carbene based on a four-membered heterocycle was described in 2004. Deprotonation of iminium salt 87a with KHMDS gave carbene dimer 88a=88a while the same reaction with 87b, bearing even bulkier N,N -substituents, led to the isolation of 88b (Scheme 1.11). Attempts to deprotonate 87a with KOt-Bu resulted in the opening of an endocyclic P-N bond, demonstrating the electrophilic character of the phosphorus atom in this compound. 

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