Hydride transfer reduction

It should be noted that compounds of this type " have been of interest as models for hydride transfer reductions in biological systems. Van Bergen and Kellogg state clearly their hope, if not expectation, that when ions such as H, Zn , Mg, etc. are com-plexed in the vicinity of the donor, beneficial catalytic effects might be forthcoming . ... 

Probably the first non-covalent immobilization of a chiral complex with diazaligands was the adsorption of a rhodium-diphenylethylenediamine complex on different supports [71]. These solids were used for the hydride-transfer reduction of prochiral ketones (Scheme 2) in a continuous flow reactor. The inorganic support plays a crucial role. The chiral complex was easily... 

In the same study, several ligands variously functional on both the nitrogen and the sulfur atoms have been developed, providing a new class of cyclo-hexylamino sulfide ligands derived from cyclohexene oxide. All the ligands depicted in Scheme 9.7 were evaluated for the Ir-catalysed hydride-transfer reduction of acetophenone in the presence of i-PrOH as the hydrogen donor, providing enantioselectivities of up to 70% ee. 

Little is known of the details of these processes. The most extensive investigations have been done with NaBH4. Studiesof the kinetics31,32,48,95 show that the reaction is first order in ketone and in hydride, that transfer of the first hydride is the slowest step, and that the alkoxyborohydrides formed in in the first step react very quickly.69 The kinetics are compatible with direct reaction between ketone and hydride or with reversible formation of a complex between the reactants folllowed by a slow hydride transfer. Reduction rates do not depend on pH,90,95 provided the solution is sufficiently alkaline for the reagent to be stable. 

Finally, the last few years have seen the first examples of the use of molecular-imprinted, polymer-supported catalysts for achieving product selectivity. The imprinted cavities are tailored in such a way that the course of a chemical reaction is directed towards one of the possible products. In the previous section it has already been shown that molecularly imprinted polymers used as microreactors are able to impart to a given reaction a different regio- and stereo-selectivity with respect to the same reaction in solution. Attempts towards an imprinted enantio-selective catalyst were reported by Gamez and co-workers who employed as template monomer an optically active, polymerisable ruthenium complex bearing in its coordination sphere an enantiomerically pure alkoxide [121]. After polymerisation, the alkoxide was split off and the resulting polymer-supported catalyst was used for enantio-selective hydride transfer reductions. The obtained selectivity was higher than for a polymer prepared without the optically active alkoxide but lower than for the same ruthenium complex in solution. 

Table 22.2 Catalytic activities for hydride transfer reduction of acetophenone and ethyl phenyl-ketone [52]...

The target reaction in this study is the reduction of prochiral ketones. In order to do this, we chose to use hydride transfer reduction to reduce phenyl alkyl ketones. This technique is attractive because high pressure and the use of H2 can be avoided. 

Figure I hydride transfer reduction of phenyl alkyl ketone...

Table I Hydride transfer reduction of different substrates ...

Kirby, A. J. Walwyn, D. R. 1987 Gazz. Chim. Ital. 117, 667—680 Effective molarities for intramolecular hydride transfer. Reduction by 1,4-dihydropyridines of the neighbouring a-ketoester group. 

Recent refinements in hydride transfer reductions have enhanced the utility of oxazaborolidine- and BINAP-Ru (II) complex-catalyzed reductions. A review by Wills describes the development of catalysts for the syntheses of chiral nonracemic secondary alcohols from aryl ketones [5]. Among the more interesting catalysts discussed were f/ -arene ruthenium complexes, which utilize diamine and monotosylated diamine ligands. 

Locatelli et al. [13] investigated the hydride transfer reduction of prochiral ketones using a rhodium based catalyst on a polyurea support. The homogeneous reduction of acetophenone using a rhodium catalyst with two equivalents of (1 S, 2 5 )-iV,iV -dimethyl-l,2-diphenylethane diamine was conducted to establish an appropriate comparison for the imprinting studies. This control reaction resulted in formation of 1-(J ) -phenyl ethanol with 67% ee (Scheme 6). The low enantioselectivity was attributed to a poor coordination sphere surrounding the metal center. The selectivity from the hydride transfer is proposed to arise from the approach of the substrate to the metal center, as shown in Scheme 7. The metal... 

Scheme 6 Homogeneous catalytic hydride transfer reduction of acetophenone. Two equivalents of a diamine ligand (L ) were added to the homogeneous reaction to serve as coordinating ligands on the rhodium center.

The synthesis of j3-ketosulphides from a-diketones is reported a key step is hydride-transfer reduction of an a-chloro-j5-ketosulphide with tri-ethylsilane (Scheme 147). 

---