Reduction of iminium salts

The reduction was studied in more detail by Cook and Schulz (52). They demonstrated conclusively that reduction of iminium salts by secondary amines is possible as illustrated in Eqs. (7) and (8). The oxidation... 

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. 

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

Reduction of Iminium Salts with Complex Hydrides... 

Quaternary ammonium cyanoborohydrides have been used for the reduction of iminium salts [14] and in the reductive amination of aldehydes and ketones [15]. 

Illustrative examples of the reductive alkylation of support-bound amines are listed in Table 10.7. Further examples have been reported [134-138]. Closely related to the reduction of iminium salts is the reduction of A-alkylpyridinium salts, which has been successfully accomplished on Wang resin using NaBH4 as the reducing agent (DMF/ MeOH (1 1), 2 x 4 h Entry 11, Table 15.23 [139]). 

Bohlmann and co-workers (11, 12) have shown that the borohydride reduction of iminium salts of type 20 gave product Q in preference to its isomer 22. These results indicate that there is stereoelectronic control in these reductions as discussed by Toromanoff (13). 

Another methods for the electrochemical formation of the active carbanion is the cathodic reduction of iminium salts. When an iminium salt is reduced in the presence of a suitable alkylating agent, an alkyl group is introduced to the carbon atom of the imine. Some isoquinoline and indole type alkaloids are synthesized by using this substitution method as exemplified bellow by the synthesis of laudanosine 51 37>. 

Yields for such reductions are in the range S0-8S %. This ready reduction of iminium salts makes possible reductive amination of aldehydes and ketones at pH 6 ... 

Reduction of iminium salt (77) is illustrated in equation (34). On hydrolysis (78) is obtained in good yield. ... 

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. 

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 major feature of interest in these borohydride reductions is that the conjugated iminium ions 118 and 120 undergo reduction exclusively by a sequential 1 6->1 4 1 2 hydride addition pathway. Since a previous report (66) on reduction of iminium salts led to the observation of exclusive 1,2-addition and no conjugate addition, further study on these systems is warranted. 

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]. 

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