Iminium addition

The 7-formyl- and 7-acetyl- pyrrolizines are formed by an iminium carboxylate intermediate followed by decarboxylation to the cyclic iminium ion which underwent nucleophilic addition followed by aldol ring closure. This pathway accounts for the 7-formyl-5-methyl [vi] and 7-acetyl-5-methyl [vii] depending if the iminium addition is by OHCCH2OH or CH3COCH2O. 

Chirality in the /V-acyl substituent can also induce stereoselectivity in the iminium addition process (equation 86). The chiral auxiliary in (115) appears to be one of the best chiral inductors and reacts with the silyl enol ether from acetophenone in 90% diastereoselectivity. It is argued that the A -acylim-inium intermediate in this reaction adopts the s-trans conformation. Similar methodology is used for the asymmetric synthesis of tetrahydroisoquinolines (equation 87). The reactive intermediate is generated through hydride abstraction from the amide by using the triphenylmethane cation. 

The formation of 88 is postulated to be occurring by the nucleophilic attack of a hydride ion (47), abstracted from the secondary amine, on the a-carbon atom of the iminium salt (89). The resulting carbonium ion (90) then loses a proton to give the imine (91), which could not be separated because of its instability (4H). In the case of 2-methyIhexamethylenimine, however, the corresponding dehydro compound /l -2-methylazacyclo-heptene (92) was isolated. The hydride addition to the iminium ion occurs from the less hindered exo side. 

A hypsochromic shift of 20-50 cm is observed in the double-bond stretching region, when the enamines are converted to the corresponding iminium salts by the electrophilic addition of a proton at the /3-carbon atom. The shift is accompanied by an enhancement in the intensity of the band. Leonard and co-workers (68,71-74) have used this absorption shift as a diagnostic tool for the determination of the position of the double bond... 

The reaction has been applied to more complex enamines 13) and to dienamines 19). The reduction may be rationalized by initial protonation at the enamine carbon and subsequent decarboxylation of formate ion and addition of the hydride ion to the iminium cation. This mechanism has been given support by the reaction of the enamine (205) with deuterated formic acid 143) to give the corresponding amines. The formation of 206 on reaction with DCOOH clearly indicates that protonation at the enamine carbon is the initial step. 

The reduction of the double bond of an enamine is normally carried out either by catalytic hydrogenation (MS) or by reduction with formic acid (see Section V.H) or sodium borohydride 146,147), both of which involve initial protonation to form the iminium ion followed by hydride addition. Lithium aluminum hydride reduces iminium salts (see Chapter 5), but it does not react with free enamines except when unusual enamines are involved 148). 

In most reviews of enamine chemistry the reactions of iminium salts are scattered throughout the review and are consequently not covered in a comprehensive manner. This chapter will be an attempt to look at reactions that, at one stage or another, proceed by nucleophilic addition to the iminium intermediate. The subject of enamines has been reviewed 1-4) and certain aspects of iminium salt chemistry such as reduction of aromatic quaternary salts have been treated in detail (5). Consequently, the reduction of aromatic quaternary salts with complex hydrides will be presented here only briefly. Although the literature (especially 1950-1967) has been checked with care, the author can make no claim to completeness. The... 

It should be noted that the products from addition to conjugated iminium salts occur primarily by 1,2-and not 1,4-addition (14). 

Another class of nucleophilic addition to iminium salts can be found in the addition of diazoalkanes. These are of great interest since they were known to add and then reaet further to form three-membered rings as in the case of C=S, C=0, and C=C functions 103). Leonard and Jann 104-106) found that treatment of iminium perchlorates with diazomethane and other diazoalkanes yielded aziridinium salts. Treatment of an iminium salt such as N-cyclohexylidinepyrrolidinium perchlorate (66) with diazomethane yielded a new product whose structure was established by spectral and chemical means to be 5-azoniadispiro[4.0.5.1]dodecane perchlorate (67). The UV spectrum was devoid of any absorption above... 

The addition of cyanide was first examined by Kaufmann(//5-7/9), who found that aromatic iminium compounds such as quinolinium methiodide (77) added potassium cyanide to give 1,4-addition product 78. 

Azides have been shown to react with itniniutn salts to give addition products. The same product is obtained if the iminium salt is treated with azide ion or if the enamine is treated with hydrazoic acid 14). The yields of the products were all very high (85-95 %). The interest in this reaction centers on the fact that the azides react with isonitriles to give substituted tetrazoles (83) 44). 

The reaction of iminium salts such as 66 with salts of trichloroacetic acid has been shown to yield amides such as 84 on hydrolysis 126). It was suggested that the reaction proceeds by addition of dichlorocarbene to give an aziridinium intermediate (85), which was opened by trichloroacetate followed by hydrolysis to give the observed products 126). The observed products from the reaction can be accounted for by formation of CCI3,... 

The reaction of enamines with ketene (146) and sulfene (147) are presumed to proceed by a two-step process involving an iminium intermediate such as 99. In fact, reaction with all electrophilic olefins such as acrylonitrile and related reagents could be thought of as going through an iminium intermediate similar to 99. Another example is given by addition to an enamine... 

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