Iminium substitution with

A wide variety of organoalkynyl derivatives of cotarnine hydrochloride, a cyclic iminium salt with rich biological activity, were prepared from the direct alkynylation of cotarnine hydrochloride using silver(l) alkynyls.180 Substituted enynes were prepared from the coupling reactions of silver alkynyls with the palladium allyl intermediates, which was... 

Perhydrooxazolo[3,2- ]pyridines 338 are excellent precursors of iminium ions 339 obtained after treatment of the oxazolidine with either a Bronsted or Lewis acid. Trapping of these intermediate iminium ions with nucleophiles then allows for substitution at the C-8a position together with ring opening, yielding functionalized piperidines 340 (Scheme 93). 

Accentuation of the p-acceptor of an enone by substitution with an iminium moiety greatly contributes to the facile intramolecular Michael addition involving an enolate. The reactive components are generated from an enollactone and an ynamine [133],... 

The stereochemistry with respect to the ketene iminium salt in cases of monosubstituted or unsymmetrically disubstituted derivatives in cycloadditions to alkenes show differences from the ketene counterpart. In contrast to ketene cycloadditions of monosubstituted ketenes with alkenes where the substituent in the bicyclic derivative ends up in the endo position, the cycloaddition of two monosubstituted ketene iminium salts with cyclopentene and cyclohexenc gives the e.wp-substituted derivatives 4.6... 

Other alkylation reactions are observed in the condensation of cyclo-propanium ions (generated in situ) with ketones 89.92)> enamines6, nitroalkanes 93>, dimethylmalonate 92>, and phenol. 92> Thus, 7-hydroxy-7-pyrrolidinobicyclo[4.1.0]heptane (56) as well as the 7,7-dipyrrolidino derivative (54) react with acetone to give the amino ketone 113. 89> This reaction may be pictured as an addition of the enol form of the ketone to the reactive iminium salt formed from the carbinol amine. In like manner, phenol undergoes ortho substitution with the carbinol amine 114 formed from cyclopropanone and dimethyl amine. 

Treatment of either the pyrrole (20) or 1-methylpyrrole (21) complex with methylacetonitrilium triflate gives the iminium-substituted 1//-pyrrole complexes 41 and 42, respectively (Figure 10).llb,12b These complexes are surprisingly resistant to deprotonation with Proton Sponge ... 

Iodo-li/-pyrrole-2-carbaldehyde, used in the synthesis of nucleoside derivatives, was prepared via protection of the aldehyde group in l//-pyrrole-2-carbaldehyde with an iminium salt for the efficient w f -directed electrophilic substitution of the starting pyrrole followed by a treatment of the iminium salt with N-iodosuccinimide in acetonitrile then with sodium bicarbonate (57% two-step total yield) <2003BML4515>. 

It was demonstrated that indole and substituted pyrroles undergo electrophilic substitution with al-kylmercaptochloromethyleneiminium chlorides giving heterocyclic iminium chlorides (122 equation Probably this reaction type is of more general applicability. 

Lateral lithiation of 244 and intramolecular electrophilic substitution with iminium ions derived from the partly reduced phthalimide 247 in acidic solution leads to the polycyclic derivatives37 such as 248. The 4-Me compound cyclises with some regioselectivity favouring para to OMe. 

Asymmetric synthesis of N-methyl-a-amino esters.2 This morpholine can be used as a chiral template for synthesis of N-methyl-a-amino esters. Thus reaction with an alkylcopper involves displacement of the phenylthio group by an alkyl group by the usual Sn2 process with inversion (about 90 10). In contrast, reaction with an alkylzinc iodide involves substitution with essentially complete retention, possibly via an iminium intermediate. The alkylated product (2) is then oxidized to an oxazinonc (3), which on treatment with vinyl chloroformate followed by hydrolysis provides N-methyl-a-amino esters (4) in high optical purity. This approach to chiral amino acids is unusual in that eiiher enantiomer can be formed from the same template depending on the choice of the organometallic reagent. Unfortunately, the chiral auxiliary (expensive) is not recovered for reuse. 

Anthrones [204] and 3-substituted oxindoles [205] possess activated methylenes which have been able to react under asymmetric iminium catalysis with a,p-unsaturated aldehydes. The reaction with 3-substituted oxindoles is especially attractive, since chiral quaternary stereocenters are generated. For this purpose, chiral primary amine thiourea catalyst 132 has been demonstrated as a very efficient promoter for the addition of 3-alkyl substituted oxindoles to P-aryl substituted enals in the presence of benzoic acid as cocatalyst in toluene at rt to afford the corresponding Michael adducts in good diastereoselectivities (dr up to >19/1) and good enantioselectivities (73-93% ee) (Scheme 2.75) [205a], P-Alkyl substituted enals are not suitable partners for the reaction affording very low diastereo- and enanti-... 

The appropriately substituted vinylogous amides can imdergo an intramolecular photocycloaddition-retro-Mannich-Mannich sequence. This sequence is analogous to the photocycloaddition-retro-aldol-aldol sequence shown in the formation of 19 from 15 (vide supra). Thus, irradiation of 110 leads to the formation of ketoimine 112, the product of photoaddition followed by rerra-Mannich fragmentation. Reaction of 112 with 1 equiv of trimethyloxonium tetrafluoroborate, followed by treatment of the resulting iminium ketone with aqueous hydrochloric acid, provides the photocycloaddition-re/ro-Mannich-Mannich product 113 in 50% yield from the acyclic photosubstrate 110. ... 

Maas, G., Rahm, R., Mayer, D. and Baumann, W., Charge dispersal in iminium-substituted alkynes - synthesis, spectral characterization, and crystal structure determination of CO2(CO)0-conplexed propyne iminium salt and structural conparison with its unconplexed counterpart, Organometallics 14 (2), 1061-1066 (1995). 

Ugi multi-component reactions of an amine, aldehyde, carboxylic acid and isocyanide (or the three-component variant with preformed imines) involve a Mumm rearrangement of an imidate in the final step, often considered the stereoselective step. However, experimental and computational evidence for kinetic control has now been reported in Ugi reactions of a o-pentose-derived pyrroline (52). The selective step is the formation of the imidate by the addition of isocyanide to the intermediate iminium ion, with the conformation of the latter determined by its substitution pattern. 

The Lewis acid promoted (typically boron trifluoride) condensation of cyclic iminium ions with TMSOF provides a facile route to a variety of substituted butenolide products. In this manner, the Lewis acid promoted condensation of pyrrolidine derived iminium ions with TMSOF provides the desired threo-product as the major isomer (eq 26). This step is pivotal in the synthesis of a tachykinin NK-2 receptor antagonist, the C1-C32 fragment of aza-solamin and various biologically active indolizidinones. ... 

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