Cascade system aldehydes

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.

Using the catalyst system described above in combination with a rhodium phosphine catalyst Lebel reported the de novo synthesis of alkenes from alcohols [100]. They developed a one-pot process, avoiding the isolation and purification of the potentially instable aldehyde intermediate. They combined the oxidation of alcohols developed by Sigman [89] with their rhodium-catalyzed methylenation of carbonyl derivatives. The cascade process is compatible with primary and secondary aliphatic as well as benzyUc alcohols in good yields. They even added another reaction catalyzed by a NHC complex, the metathesis reaction, which has not been addressed in this review as there are many good reviews, which exclusively and in great depth describe all aspects of the reaction. 

Moreover, a controlled number of anionic zirconocene units can be selectively introduced into the internal layers of a polydendritic macromolecule. The reaction of the multidendritic system 24-G3G2, constituted by a central dendrimer of generation 3 and by six internal dendrimers of generation 2 possessing 24 internal aldehyde groups, with 16 a (excess) clearly leads to the polyzwitterionic zirconocene polydendritic structure 25-G3G2 in which all the early transition metal anions are located within the cascade structure (Scheme 6). 

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. 

Similar conformational preferences are expected to apply to iminium ions, one of the key intermediates in many organocatalytic cascades. When snch iminium ions undergo deprotonation, the reactive conformation is the one where the breaking C-H bond is aligned with the iminium jt-system. In the presence of additional stereocenters that make the two sides of the Jt-system diastereotopic, the proton abstraction occurs from the stericaUy more accessible face opposite to the catalyst sidechain. As a result, the opposite enantiomers of chiral aldehydes are transformed into opposite enamine stereoisomer (E- or Z-, Figure 6.39). This stereochemical relationship is maintained in the reverse process which involves protonation on the less hindered face of the enamine. Eventual equihbration of the E and Z enamines is possible but relatively slow. ... 

The one-pot synthesis of 2-substituted-3-carboxychromones is readily attained by the reaction of 3-oxo-3-(2,6-di luorophenyl)propanoates and acyl chlorides (13CC5313) and of 3-[2-(methoxymethoxy)phenyl]propio-lates and aldehydes followed by DDQ oxidation of the formed chroma-nones (13T647), via transition metal-free approaches. Palladium(II) -catalyzed cascade carbonylative cyclization of 2-bromophenols and terminal alkenes gives chromones 44 in moderate to good yields. Variation on the amine used in the catalytic system led to aurones 45 as major products (Scheme 74) (13TL1802). 

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... 

Coldham and coworkers reported a tandem condensation/cyclization/intramolec-ular cycloaddition cascade process to form fused tricychc amines, using azomethine ylides (derived from a-amino-acids or esters). This chemistry was apphed for the constmction of the pyrrolo[l,2-a]azepine ring system of the Stemona alkaloids (Scheme 4.20) [39]. Condensation of the aldehyde 96 bearing a dipolarophile (an... 

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... 

Af-alkyl-Af-phenylacrylamides and aryl aldehydes undergo oxidative cascade coupling reaction to 3-(2-oxo-2-arylethyl)mdolin-2-ones in good yields using CUCI2/TBHP as catalyst and oxidant, respectively. Both the C(sp2)-H of the Af-alkyl-Af-phenylacrylamides and C(sp )-H bonds of the aldehyde were activated in one step under this oxidative system. The acyl radical which is generated from... 

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