Cascade system unsaturated aldehydes

In 2011, Enders et al. reported a sequential organocatalytic cascade reaction between a,p-unsaturated aldehydes and p-oxosulfones, using a combination of a chiral diaiylprolinol trimethylsilyl ether and an achiral N-heterocyclic carbene as a catalytic system. This sequential... 

Two C-C Bond-Forming Events In 2008, Frechet and coworkers described an impressive asymmetric cascade reaction promoted by soluble star polymers with core-confined catalytic entities [10]. The encapsulation of catalysts into soluble star polymers allowed the use of incompatible catalysts and prevented undesired interactions between these catalytic systems. The organocascade corresponded to a nucleophilic addition of Af-methylindole to a,p-unsaturated aldehydes followed by a Michael addition of the adduct to methylvinylketone (MVK) in the presence of H-bonding additive (Scheme 12.5). Each catalyst - imidazolidinone 8 for the nucleophilic addition and diphenylprolinol methyl ether 9 for the Michael addition - or their combination cannot mediate both reaction steps. In particular, p-toluenesulfonic acid (p-TSA) diminished the ability of the chiral pyrrolidine 9 to effect enamine activation. Therefore, p-TSA and 9 were encapsulated in the core of star polymers, which cannot penetrate each other. Imidazolidone 8 was added to the acid star polymer and diffused to the core to form the salt, which allowed the iminium activation and catalyzed the first step. The second step was catalyzed by the pyrrolidine star polymer in presence of the H-bonding additive 10, which... 

The combination of a chemoselective enzymatic reduction step with another second enzymatic reaction is another opportunity to overcome limitations, for example, in the case of the enantiosdective reduction of prochiral unsaturated aldehydes by coupling a reduction step with an isolated ene reductase (OYE 2 or OYE3) together with an oxidation step with HLADH in a cascade system, which allowed both yields and enantioselectivities to be improved [136]. 

Scheme 11.11 Bioreduction of prochiral unsaturated aldehydes to either saturated aldehydes (left) or saturated alcohols (right) by either an isolated ene reductase (OYE2) or a OYE2-ADH cascade system, respectively.

The Kim group envisioned that the saturated aldehydes 19 might also be used as viable substrates for asymmetrie [l,5]-hydride transfer/cyelization reactions by coupling the in situ generation of the o,p-unsaturated imin-ium intermediate 22 by oxidation (Seheme 4.11a). IBX (2.0 equiv.) was found to be the suitable organie oxidant compatible with the established catalytic system (20 mol% of C3 and 20 mol% of DNBS) for the asymmetric [l,5]-hydride transfer reactions. This novel cascade reaction also allows the efficient synthesis of ring-fused tetrahydroquinoline products with high enantioseleetivity. 

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