Transfer hydrogenation of a,P-unsaturated aldehydes

Yang JW, Fonseca MTH, Vignola N, List B (2005) Metal-Free, Organocatalytic Asymmetric Transfer Hydrogenation of a,P-Unsaturated Aldehydes. Angew Chem Int Ed 44 108... 

Ru/tppms catalysts exhibited excellent yields (98%) in the transfer hydrogenation of unsaturated aldehydes such as cinnamaldehyde or crotonaldehyde, to the corresponding unsaturated alcohols under mild reaction conditions (30-80°C), with HCOONa in an aqueous/organic two phase system. Similarly, ruthenium modified with the water soluble, air stable phosphine 100 (pta Table 5) is an effective catalyst for the chemoselective transfer hydrogenation of a,P-unsaturated aldehydes to unsaturated alcohols using formate in an aqueous/ organic two phase system. In contrast, Rh/pta afforded the cor-... 

High catalytic activities, with turnovers of up to 9(X) cycles min , is displayed in the transfer hydrogenation of a,p-unsaturated ketones, such as benzylideneacetone and chalcone, using 2-propanol and catalytic amounts of [Ir(3,4,7,8-Me4-phen)COD]Cl (phen = 1,10-phenanthroline COD = 1,5-cyclo-octadiene) in a weakly alkaline medium. Other Ir-chelated complexes are also active catalysts in this reaction, with over 95% selectivity for the 1,4-reduction mode. Divalent lanthanide derivatives, such as Sml2 or Ybh in stoichiometric quantities, in THF and t-butyl alcohol or methanol reduce ethyl cinnamate and cinnamic acid to give the saturated derivatives. " Similarly, 3-methylcyclohexenone is reduced to 3-methylcyclohexen-l-ol in 67% yield, but a,p-unsaturated aldehydes are nonselectively reduced with these systems. 

List was the first to explore this possibility, examining the Hantzsch ester mediated reduction of a,P-unsaturated aldehydes [209], Using 20 mol% of the binaphthyl derived phosphonate salt of morpholine (153) in dioxane at 50 °C, a series of P-aryl a,P-unsaturated aldehydes underwent transfer hydrogenation with Hantzsch ester 154 with excellent levels of absolute stereocontrol (96-98% ee) (Scheme 63). The method was also applied to the aliphatic substrates ( )-citral and famesal to give the mono-reduced products in 90% and 92% ee, respectively. Significantly, in line with many of the chiral secondary amine catalysed transformations described above the reactions follow a simple and practical procedure without the need for exclusion of moisture and air. 

Various a,P-unsaturated aldehydes were also selectively reduced to give allylic alcohols by this catalytic system (Scheme 5.19). The transfer hydrogenation of ali-... 

Aromatic aldehydes and DMF can serve as hydrogen donors and transfer their formyl hydrogen to a,p-unsaturated ketones in the presence of RuCl2(PPh3)3. However, in some cases, decarbonylation of the aldehyde is so severe that no transfer hydrogenation is observed. 

Nature makes use of NADH (reduced nicotinamide adenine dinucleotide) as a cofactor for enantioselective biochemical hydrogenations, which are typical hydride-transfer reactions. Dihydropyridines and benzimidazolines derivatives are active hydride donors due to the presence of the nitrogen atom and the ability of the molecule to undergo aromatisation. Organocatalytic enantioselective reductions carried out using hydride donors has been studied, and effective reductions have been achieved with imidazoli-dinone organocatalysts, both with a,p unsaturated aldehydes and ketones. Generally, a stoichiometric quantity of reductant (Hantzsch ester 4) is required for these transformations (Scheme 18.5). 

On the other hand, the use of chiral anions in conjunction achiral or chiral ammonium ion catalysts has been pioneered by List and co-workers. In 2006, Mayer and List [ 166] hypothesized that catalytic salts of achiral amines and chiral phosphoric acids could induce asymmetry in the transfer hydrogenation of p,p-disubstituted-a,p-unsaturated aldehydes, in a process that would be complementary to the previously developed chiral iminium catalysis (see Section 2.2.1.4) of this process [68,167]. The experimental verification of this hypothesis demonstrated that excellent yields and enantioselectivities (90-98% ee) could be achieved in these hydrogenations. The fact that with an achiral secondary amine such as morpholine the process was highly stereoselective led the authors to postulate that ion-pairing and not Brpnsted acid... 

Transfer hydrogenation followed by alkylation of oc,P-unsaturated aldehydes mediated by a combination of cycle-specific catalysts of 115 and ent-196 was also developed [135]. 

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