Sodium/ions cyanoborohydride

To a solution of 5 g of sisomicin in 250 ml of water add 1 N sulfuric acid until the pH of the solution is adjusted to about 5. To the solution of sisomicin sulfuric acid addition salt thereby formed, add 2 ml of acetaldehyde, stir for 10 minutes, then add 0.B5 g of sodium cyanoborohydride. Continue stirring at room temperature for 15 minutes, then concentrate solution In vacuo to a volume of about 100 ml, treat the solution with a basic ion exchange resin [e.g., Amberlite IRA401S (OH )], then lyophilize to a residue comprising 1-N-ethyl-sisomicin. 

Rather than preforming the a-amino ketimines to be reduced, it is often advantageous to form in situ the more reactive iminium ions from a-aminoketones and primary amines or ammonium salts in the presence of the reducing agent, e.g., sodium cyanoborohydride. Use of this procedure (reductive amination) with the enantiopure a-aminoketone 214 and benzylamine allowed the preparation of the syn diamines 215 with high yields and (almost) complete diastereoselectivities [100] (Scheme 32). Then, the primary diamines 216 were obtained by routine N-debenzylation. Similarly, the diamine 217 was prepared using ammonium acetate. In... 

Indolines are produced in good yield from 1-benzenesulfonylindoles by reduction with sodium cyanoborohydride in TFA at 0°C (Equation 5) (89TL6833). If acyl groups are present at C-2 or C-3 in the substrate, they are reduced to alkyl groups. Indole is also reduced to 2,3-dihydroindole by sodium cyanoborohydride and acetic acid or triethylamineborane and hydrochloric acid. An alternative method for preparing indolines involves treatment of indoles with formic acid (or a mixture of formic acid and ammonium formate) and a palladium catalyst (82S785). Reduction of the heterocyclic ring under acidic conditions probably involves initial 3-protonation followed by reaction with hydride ion. 

This rationalization indicates that internal delivery of a hydride is not a requisite for the observed stereospecificity. Reduction of the oxonium ion with an external hydride reagent should also give equatorially oriented bicyclic ether only. Accordingly (112), reduction of tricyclic spiroketal 145 with sodium cyanoborohydride at pH =3-4 yields only the equatorial bicyclic ether alcohol (J47, CHO=CH2OH). Eliel and co-workers (113) have previously suggested that the orientation of the electron pairs of oxygen atoms influence the course of the reduction of 2-alkoxytetrahydropyran with lithium aluminium hydride-aluminium trichloride. 

Stevens and Lee (16) have recently completed a stereospecific synthesis of ( )-monomorine (28). In the last step of this synthesis, the piperidinium ion 27 was reduced with sodium cyanoborohydride to give only (t)-monomorine (28). 

Reduction of vinylogous carbamate 36 with sodium cyanoborohydride in acidic methanol gave exclusively the equatorial aminoester 38. Eschenmoser and co-workers (181 have explained this result by invoking a stereoelectroni-cally controlled anti peri planar addition of hydride ion on the iminium ion 37. 

This can be done in two steps, provided the intermediate is stable, but, because the instability of many imines makes them hard to isolate, the most convenient way of doing it is to form and reduce the imine in a single reaction. The selective reduction of iminium ions (but not carbonyl compounds) by sodium cyanoborohydride makes this possible. When NaCNBH3 is added to a typical imine-formation reaction it reacts with the products but not with the starting carbonyl compound. Here is an example of an amine synthesis using reductive amination. 

Catalytic hydrogenation reduces the imine (as the protonated iminium ion) but not the ketone from which it is formed. This chemoselectivity (reduction of iminium ions but not ketones) is also displayed by sodium cyanoborohydride and we can add NaCNBH3 to complete our table of reactivity, if we insert imines at the left-hand end. 

In the laboratory of J. Kobayashi, the biomimetic one-pot transformation of serratinine into serratezomine A was accomplished using the Polonovski-Potier reaction Serratinine was first treated with m-chloroperbenzoic acid to obtain the A/-oxide, and then excess TFAA was added. The iminium ion was formed in the following fashion the C13 hydroxyl group formed a hemiacetal with the C5 carbonyl group and simultaneously with the formation of the C5-C13 lactone the C4-C5 bond was broken. The iminium ion was then reduced with sodium cyanoborohydride to afford the tertiary amine functionality. Besides serratezomine A, another lactone (between the C8 hydroxyl and C5 carbonyl) was formed in 27% yield. 

LACTAMS Di-n-butyltin oxide. Hy-droxylamine-O-sulfonic acid. Iodine azide. Sodium cyanoborohydride. (3-LACTAMS Cyanuric chloride. Grignard reagents. Ion-exchange resins. Lithium phenylethynolate. Sodium dicarbonyl-cyclopentadienylferrate. Titanium(III) chloride. Titanium(IV) chloride. Tri-phenylphosphine-Carbon tetrachloride. Triphenylphosphine-Diethyl azodicar-boxylate. Triphenylphosphine-2,2 -Dipyridyl disulfide. 

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