Regional Issue "Organic Chemistry in Argentina" ARKIVOC 2011 (vii) 182-194
R1 R3 R1R3 H+H2O R1 R3 R1 R3
[H] O
N R2 R4
HN R2 NN
R4 R2R4 R2R4
OH
H+ H2O
Scheme 1. Reductive amination reaction.
The reaction can be carried out either in a “one-pot” system, where the formation of the imine and its reduction product occur in only one operational stage, or stepwise, where the intermediate imine is isolated, and reduced in a second stage.
The selection of reducing agents in this type of reactions is critical, since they must reduce selectively the imine without affecting significantly the original carbonyl compound or other reducible groups present. A large number of reducing agents have been developed, though many of them present unwanted properties in terms of selectivity, secondary reactions, reaction conditions, safety hazards, and toxicity.
The catalytic hydrogenation is the most employed reductant for imines in large scale syntheses,3 although it is limited to molecules which do not carry double bonds or other reducible groups under hydrogenation conditions. For laboratory scale, sodium cyanoborohydride (NaBH3CN), among other hydrides, is the reagent most employed for reductive amination:4 it is highly selective, soluble in many solvents, and stable in acid medium (up to pH 2).1 Cases et al.5 found that the optimum pH for the reductive aminations of galactose and 1-amino-2-propanol was 4. Nevertheless, NaBH3CN generates highly toxic products such as HCN or NaCN during the reaction or work-up, and thus should not be recommended for medium or large scale reactions, and even less in the actual context of “green chemistry”. Sodium triacetoxyborohydride (NaBH3(OAc))6 has also been employed, but mostly in non-protic solvents, since in methanol or water it reduces the carbonyl groups, decomposes, and gives flammable subproducts.7 Pyridine borane (Pyr-BH3)8-10 was the most representative aminoborane employed, but it is unstable, and decomposes causing fire; even explosions were reported.11
Following an initial finding of Oshima and coworkers,12 we have developed in our lab a technique for the chromatographic resolution of enantiomeric sugars by reductive amination with chiral amines (i.e. by generation of diastereomers), using NaBH3CN as the reducing agent.5,13 However, we decided now to try another less toxic reductant: the substitute chosen was the •picoline borane (Pic-BH3, Scheme 2). This reagent appeared on the market in 2004.11 Sato et al. showed its smooth working conditions in different solvents (including water), no generation of toxic wastes, stability up to 150ºC, high selectivity and low cost.11 The use of water in the reaction medium would be a remarkable advantage, especially at an industrial level.
Herein, we introduce the use of •-picoline borane as a replacement of sodium cyanoborohydride in the reductive amination employed for the determination of the absolute configuration of the monosaccharides present in polysaccharides or glycosides, and its extension to the synthesis of aminodeoxyalditols in larger amounts.
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