Reduction, of iminium salts, with

Reduction of iminium salts with diborane and by the Meerwein-Ponndorf method have been reported (89). 

Reduction of Iminium Salts with Complex Hydrides... 

Table 6. Enantiomeric excess in 3,3,5-trimethylcyclohexanone from the reduction of iminium salts with 1,4-dihydronicotinamide sugar...

Baba N, Nishiyama K, Oda J, Inouye Y (1976) Asymmetric reduction of iminium salt with chiral dihydropyridines. Agric Biol Chem 40 1441-1 443... 

The reduction of iminium salts can be achieved by a variety of methods. Some of the methods have been studied primarily on quaternary salts of aromatic bases, but the results can be extrapolated to simple iminium salts in most cases. The reagents available for reduction of iminium salts are sodium amalgam (52), sodium hydrosulfite (5i), potassium borohydride (54,55), sodium borohydride (56,57), lithium aluminum hydride (5 ), formic acid (59-63), H, and platinum oxide (47). The scope and mechanism of reduction of nitrogen heterocycles with complex metal hydrides has been recently reviewed (5,64), and will be presented here only briefly. 

Synthesis of tertiary amines. Mercuric acetate reacts with an enamine (1) in DMF by attack at the J3-carbon atom to afford an iminium salt (2). Reduction of the salt with sodium borohydride gives the corresponding tertiary amine (3). Yields are in the range 50-90%. 

Reduction of iminium salts. 1,3-Diamines can be elaborated via reduction of the monoiminium species which arise from condensation of enamines with aldiminium salts. The subsequent reduction is carried out with NaBH, in methanol. Oximes of a-aminocycloalkanones undergo fragmentation and reduction, furnishing co-amino nitriles. A route to substituted ureas involves reductive alkylation, condensation with aldehydes in the presence of MejSiCl followed by treatment with NaBH. The borohydride reduction of P-amino-a,P-unsaturated esters in the presence of isobutanoic acid may also proceed via iminium species. 

The ability to reduce compounds under acidic conditions is ideal for the reduction of enamines. Protonation of nitrogen gives an iminium salt in acidic media that is then reduced with cyanoborohydride to an amine.Imines can be reduced in acidic media in the presence of many other functional groups, as shown by Cook s reduction of imine 165 to give 166 in 79% yield in a synthesis of substituted tetrahydro-P-carbolines. 2 This reagent is excellent for the reduction of iminium salts at neutral pH as well,l 3 and it is also useful for the reductive alkylation of amines. Dimethylamino derivatives such as 168 can be prepared from the amine (167 in this case) by treatment with formaldehyde and cyanoborohydride, even in the presence... 

In 1982, Ohga and Mariano first reported the photoallylation of iminium salts. The photoreaction of iminium salts with allyl-trimethylsilane in acetonitrile affords allylated compounds via the addition of an allyl radical to an a-aminomethyl radical. Allyl radicals are produced via the cleavage of C-Si bonds of allylsilane radical cations and the a-aminomethyl radicals are generated by one-electron reduction of iminium salts as shown in Scheme 4. 

In addition, good results were reported for the synthesis of new mono-N-tosylated diamine ligands based on (/f)-(+)-limonene and their application to ATH of cyclic imines and iminium salts, with up to 98 % e.e. in some cases [69]. Reductions of iminium salts have been described with the use of 1.2 mol% of a Ru(II) catalyst, using sodium formate with cetyltrimethylammonium bromide (CTAB) in aqueous solution, with the addition of silver hexamethylantimonate [38]. 

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... 

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 intermediate formation of iminium salts is postulated in the reduction of (x-amino ketones by the Clemmensen method, occurring with concomitant ring enlargement or contraction (244-246). Reduction of l,2,2-trimethyl-3-piperidone (154) in this manner gave l-methyl-2-iso-propylpyrrolidine (155). 

Recently, Malpass et al. reported a synthesis of epibatidine isomers also under reductive Heck conditions [134, 135]. 2-Azabicyclo[2.2.1]heptene 167 was assembled by cycloaddition of an iminium salt with cyclopentadiene. Treatment of 167 with 2-chloro-5-iodopyridine provided a mixture of exo-5-(6-chloro-3-pyridyl) derivative 168 and exo-6-(6-chloro-3-pyridyl) derivative 169. 

One application of lactone 140 as a chiral synthon may be found in the asymmetric synthesis of (+)-12b-epidevinylantirhine (143), a cleaved product of geissoschizol (Scheme 28) [62-63]. Treatment of 140 with tryptamine in hot toluene afforded 142, which cyclized to lactam 142 by mesylation and an Sn2 displacement. Hie Bischler-Napieralski reaction of 142, followed by reduction of the resulting iminium salt with NaBH4, produced stereoselectively, the indolo[2,3-a]quinolizine as a single isomer, which was further reduced with DIBAL to give (+)-12b-epidevinylantirhine (143). 

Oxidative cyclization. The final step in a synthesis of racemic ajmalicine (2) required oxidative cyclization of (I). This reaction was carried out in 2.5% aqueous acetic acid with an excess of 1 1 mercuric acelale-ethylenediaminetetraacetic acid disodium salt (EDTA, I, 373-374) followed by sodium borohydride reduction of iminium intermediates. 

Table 6 Stereochemistry of Reduction of 2-MethylcyclohexyI Imines and Iminium Salts with Hydride Reagents... 

Addition to cyclic iminium salts has been utilized in alkaloid synthesis. A zinc-promoted reductive coupling reaction of iminium salts and alkyl halides has been reported by Shono et al. (Scheme 8). Evidence delineating the mechanistic course (organozinc addition or electron transfer reaction) of the addition has not been established. In contrast to organolithium or Grignard additions, aromatic halogen and alkoxycarbonyl substituents are compatible with this methodology. The intramolecular version of this reaction has been employed for the synthesis of tricyclic amines (53 equation 9). 

As summarized already in the introduction these iminium salts of fluoral are readily available either with trifluoroacetic acid anhydride (TFAA) and N-oxide of trifluoroethylamine (Potier-Polonowsky reaction, ref. 15) or from N-0 or N-S acetals formerly accessible by electrochemical amine oxidation and now by hydride reduction of thioamidinum salts (ref. 11). 

The biomimetic reduction of other iminium salts with NAD+ coenzymes has also been studied30-32. 

Baba N, Makino T, Oda J, Inouye Y (1980e) Asymmetric reduction of a,3-unsaturated iminium salts with 1,4-dihydronicotinamide sugar pyranosides. Can J Chem 58 387-392... 

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