Iminium ions, and

Scheme 19 Asymmetric synthesis of 2-(l-aminoalkyl)pyrrolidines and 2,2 -dipyrrolidines from chiral imines and iminium ions...

Imines and iminium ions are nitrogen analogs of carbonyl compounds and they undergo nucleophilic additions like those involved in aldol reactions. The reactivity order is C=NR < C=0 < [C=NR2]+ < [C=OH]+. Because iminium ions are more reactive than imines, the reactions are frequently run under mildly acidic conditions. Under some circumstances, the iminium ion can be the reactive species, even though it is a minor constituent in equilibrium with the amine, carbonyl compound, and unprotonated imine. 

A variety of double bonds give reactions corresponding to the pattern of the ene reaction. Those that have been studied from a mechanistic and synthetic perspective include alkenes, aldehydes and ketones, imines and iminium ions, triazoline-2,5-diones, nitroso compounds, and singlet oxygen, 10=0. After a mechanistic overview of the reaction, we concentrate on the carbon-carbon bond-forming reactions. The important and well-studied reaction with 10=0 is discussed in Section 12.3.2. 

The starting material was prepared with the modification on the epibatidine bicychc ring system by repositioning the nitrogen atom to a methylene group. We carried out the Hetero-Diels Alder reaction of cyclopentadiene and iminium ion generated from ammonium chloride and formaldehyde in the aqueous medium and protected resulted unstable secondary amine with benzoyl chloride to provide (3) in good yields [5] (Scheme 38.1). 

We saw in Section 7.7.1 that imines and iminium ions could act as carbonyl analogues and participate in nucleophilic addition reactions. 

Scheme 35 Enamines and iminium ions in organocatalytic domino reactions...

The conjugate addition of nitroalkanes to a,P-unsaturated aldehydes (Sect. 2.2.2) has been investigated by Uggerud, who compared the uncatalysed, proton catalysed and iminium ion catalysed additions [232]. The results suggested that protonated acrolein was more activated towards addition than the iminium ion catalysed process and also indicated that an intermediate oxazolidin structure 183, unobserved experimentally, may be involved in the reaction pathway (Fig. 17) with the transition state resembling that of a [3+2] cycloaddition process. 

Enamine carbaldehyde 76 (Scheme 20) by sequential photochemical cycloaddition and iminium ion-propargylsilane cyclimtion furnishes allenes 77a-c in good yield and with high diastereoselectivity (92X2081). (Gas chromatographic fR values and thin-layer chromatographic Rp values have been reported.) Radical cyclization of ca-iodoalkyl isoquinolone 78a under... 

SECTION 2.2. ADDITION REACTIONS OF IMINES AND IMINIUM IONS... 

A quinazoline alkaloid skeleton has been synthesized by means of the Rh-catalyzed cyclohydrocarbonylation of diaminoalkenes. The reaction of 2-(A -allylaminomethyl)aniline 55 gave quinazoline 59 in excellent yield through the highly linear-selective hydroformylation of 55 to aldehyde 56, followed by the sequential formations of hemiaminal 57 and iminium ion 58 as intermediates and then the subsequent intramolecular amine addition (Scheme In the same manner, the reaction of A -allyl-2-aminomethylaniline 60 afforded 61 in 96% yield. ... 

This reaction is believed to proceed via nucleophilic combination of in situ generated Cu-acetylide and iminium ion. Mechanistic studies indicate a strong positive non-linear effect based on which a catalytic cycle is proposed that involves a dimeric Cu/quinap complex as the active catalytic species. 

Christie, B. D. Rapoport, H. Synthesis of optically pure pipecolates from L-asparagine. Application to the total synthesis of (+)-apovinc-amine through amino acid decarbonylation and iminium ion cyclization. J. Org. Chem. 1985, 50, 1239-1246. 

Despite the fact that the intermediates in this reaction are pictured by the authors as hydrogen sulfates, they perhaps would be better represented as the hydrogen sulfate salts of nitrilium and iminium ions, respectively. 

Electrophilic substitutions of alkenyl-, aryl-, and alkynylsilanes with heteroatom-stabilized cationic carbon species generated by the action of a Lewis or Brpnsted acid (acyl cation, oxocarbenium ion, etc.) provide powerful methods for carbon-carbon bond formation. Particularly, intramolecular reactions of alkenylsilanes with oxocarbenium and iminium ions are very valuable for stereoselective construction of cyclic ether and amine units.21-23 For example, the BFj OEt -promoted reaction of (E)- and (Z)-alkenylsilanes bearing an acetal moiety in the alkenyl ligand gives 2,6-disubstituted dihydropyrans in a stereospecific manner (Scheme l).23 Arylsilanes also can be utilized for a similar cyclization.24... 

In the forward synthesis, it turned out that the nitrile reduction was best done using hydrogen and a metal (Rh) catalyst, The final methylation of the primary amine had to be done via the imine and iminium ion (see Chapter 24) to prevent further unwanted alkylations. The reagent was an excess of formaldehyde (methanal CH2=0) in the presence of formic acid (HCO2H),... 

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