Polymer-supported borohydride reduction

The N-substituted aminoacids required could be prepared by microwave-assisted reductive amination of aminoacid methyl esters with aldehydes, and although in the Westman report soluble NaBH(OAc)3 was used to perform this step, other reports have shown how this transformation can be performed in using polymer-supported borohydrides (such as polymer-supported cyanoborohydride) under microwave irradiation [90]. An additional point of diversity could be inserted by use of a palladium-catalyzed reaction if suitably substituted aldehydes had been used. Again, these transformations might eventually be accomplished using supported palladium catalysts under microwave irradiation, as reported by several groups [91-93]. 

Aryl azides are converted into the corresponding anilines by polymer-supported borohydride [33]. Simple aliphatic azides are not reduced under similar conditions and the reduction of benzyl azides is slow. 

In addition, supported reagents have been demonstrated to be effective under reaction conditions when either thermal or microwave heating - is employed. They have also been utilised in traditional batch synthesis, stop-flow methods and continuous flow processes. ° However, one caveat is that the immobilisation of reagents can change their reactivity. For example, polymer-supported borohydride selectively reduces a,P-unsaturated carbonyl compounds to the a,P-unsaturated alcohoF in contrast to the behaviour of the solution-phase counterpart, which additionally causes double bond reduction. 

One of the most widely used supported reagents for reduction is polymer-supported borohydride. An interesting example is the final step of the total synthesis of polysphorin 55, an anti-malarial natural product (Scheme 4.15) [62]. The stereoselective reduction of ketone 54 occurred with excellent diastereomeric excess when PS-BEMP was used, affording the 55 in 90% yield. 

Devaky and Rajasree have reported the production of a polymer-bound ethylenediamine-borane reagent (63) (Fig. 41) for use as a reducing agent for the reduction of aldehydes.87 The polymeric reagent was derived from a Merrifield resin and a 1,6-hexanediol diacrylate-cross-linked polystyrene resin (HDODA-PS). The borane reagent was incorporated in the polymer support by complexation with sodium borohydride. When this reducing agent was used in the competitive reduction of a 1 1 molar mixture of benzaldehyde and acetophenone, benzaldehyde was found to be selectively reduced to benzyl alcohol. 

A polymer-supported lipoamide-ferrous chelate system was used as catalyst for the reduction of diphenylacetylene to cis-stilbene with sodium borohydride the dithiol-iron(II) (1 1) complex formed was suggested to be the active species. The chitosanlipoamide system has the highest activity among various insoluble polymers investigated 95,96). 

The use of numerous polymer-supported optically active phase transfer catalysts was further extended by Kelly and Sherrington11351 in a range of phase transfer reactions including a variety of displacement reactions, such as sodium borohydride reductions of prochiral ketones, epoxidation of chalcone, addition of nitromethane to chalcone and the addition of thiophenol to cyclohexanone. Except in the chalcone epoxidation, all the examined resin catalysts proved to be very effective. However, with none of the chiral catalyst system examined was any significant ee achieved. The absence of chiral induction is a matter of debate, in particular over the possible reversibility of a step and the minimal interaction within an ion pair capable of acting as chiral entities in the transition state and/or the possible degradation of catalysts and leaching. 

Although the catalytic asymmetric borane reductions mentioned above are a powerful tool to obtain highly enantio-enriched alcohols, these require the use of a rather expensive and potentially dangerous borane complex. Sodium borohydride and its solution are safe to handle and inexpensive compared to borane complexes. Thus sodium borohydride is one of the most common industrial reducing agents. However its use in catalytic enantioselective reductions has been limited. One of the most simple asymmetric catalysts is an enantiopure quaternary armnonium salt that acts as phase-transfer catalyst. For instance, in the presence of the chiral salt 81 (Fig. 9), sodium borohydride reduction of acetophenone gave the secondary alcohol in 39% ee [124]. The polymer-supported chiral phase-transfer catalyst 82 (Fig. 10) was developed for the same reduction to give the alcohol in 56% ee [125]. 

In a more recent study, polymer-bound borohydride was used for reductive ami-nation of tetrameric isoquinolines [116]. These tetrameric isoquinolines, serving as lead compounds in research to find antibacterial distamicyn A analogues, have been prepared from the corresponding isoquinoline, imidazole, and pyrrole building blocks by standard amide bond formation reactions. The final derivatization by reductive amination was efficiently accelerated by microwave irradiation in the presence of Merrifield resin-supported cyanoborohydride (Scheme 16.76). 

The TOP sequence can also be carried out in the presence of a heterogeneous reductant to effect an oxidation-imination-reduc-tion process leading from activated alcohols to amines (eqs 86 and 87). Polymer-supported cyanoborohydride (PSCBH) or sodium borohydride can be used as the reductant. The use of an oxidant and reductant in the same one-pot procedure is noteworthy. 

The first observation in the plicamine synthesis of note is that the polymer-supported hyper-valent iodine reagent, mentioned earlier, again performed well to convert phenol 28 to spirodienone 29. Nafion-H (fluorosulfonic acid resin) catalyzed the final cyclization of 29 to form the tricyclic core of the natural product in virtually quantitative yield. After stereo- and regioselective reduction of 30 using supported borohydride, the highly hindered intermediate alcohol was methylated by... 

Hyperbranched PEI or functionalized PEIs with glycidol (PEI-GLY), glu-conolactone (PEI-GLU) or lactobionic acid (PEI-LAC) have been used as support materials for metal nanoparticles in water. Polymer-stabilized metal nanoparticles were prepared in a two-step process. After complexation of the metal ions with the respective polymer in a first step, a chemical reduction with sodium borohydride was performed in a second step to obtain the metal... 

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