Graphene Oxides as Organocatalyst

Nanosheets of graphene oxides display outstanding physical, chemical and electrical charasteristics and this is why this material has attracted a lot of interests in the chemical community. The presence of OH and free caroboxyl moieties on the surface renders this material water soluble, and this is a great pratical advantage.  

In a short Chem Comm paper (DOI: 10.1039/c1cc15230k), indian researchers reported the use of graphene oxide as organocatalyst for an aza-Micheal reaction. The graphene oxide was synthesized by oxidation of graphene powder and fully characterized from the spectroscopical point of view (XRD, FTIR, UV-Vis). Subsequently the catalytic potential of graphene oxide nanosheets was examined for the aza-Michael addition of amine to activated olefines.

 

The reaction was defenitly influenced by the presence of grapgene oxide in catalytic amount and the full conversion could be obtained after only 5 minute of reaction time. The responsible for this huge activation are the oxigen containing functionalities on the surface of graphene oxide: in fact, the same reaction carried out in presence of reduced graphene was completed after a longer period of time (30 min). 

Moreover, by a simple extraction, the graphene oxide could be recovered from the reaction mixture and reused for the same reaction without loss in yield or ee.

This discovery opens new horizons in the application of graphene oxide os organocatalyst. 

 

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Oxindoles Again!

 Spirooxindoles in one step!

 DOI: 10.1021/ol300441z

If you just leaf through an organic chemistry journal, from JOC to Organic Letters, from EJOC to OBC, there is a huge number of papers describing synthesis of oxindoles! Indeed, the interest in the oxindoles scaffold rapidly increased in the last years and several methodologies have been published for the asymmetric synthesis of 3,3’-disubstituted oxindoles.

Cascade organacatalysis is a powerful tool for the for the asymmetric synthesis of very complex structures containing several stereogenic centers and oxindoles are optimal templates for the applications of these wonderful catalytic methodologies. For example, prof. Paolo Melchiorre, one the most expert in the organocatalysis field, published several works in the application of organocascade catalysis for the synthesis of quaternary oxindoles.

In this communication, Carlos Barbas, another pioneer of organocatalysis, reported a quindine-catalyzed synthesis of spirooxindoles through sequential Michael-Henry reactions.

They first performed a preliminary methodological study aimed at finding the most efficient catalyst, which turned out to be quindine derivative depicted below.

Subsequently the scope of the reaction has been expanded, by employing a wide range of substituted oxindoles, as well as different nitrostyrens. Performing the reaction at 0°C in CH2Cl2 as solvent in presence of quinidine derivative 1 permitted the isolation of the products in very high yield and optimal enantiomeric excess and diastereoisomeric ratio.

It is noteworthy to mention that this simple methodology permits the straightforward construction of the spirooxindole moiety containing four stereogenic centers,, with full control of the stereochemical outcome. This is another demonstration of the powerful of organocatalysis. 

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Asymmetric Knoevenagel

The Catalytic Asymmetric Knoevenagel Condensation

Anna Lee, Anna Michrowska, Sarah Sulzer-Moss, Benjamin List

Angew. Chem. Int. Ed. 2011, 50, 1707 –1710

The Knoevenagel condensation is a powerful method for the formation of C-C bonds. Up to now there wasn’t any asymmetric version, neither by using chiral auxiliaries nor with catalysts. Recently List et al reported the first asymmetric Knoevenagel condensation that proceeds through dynamic kinetic resolution of alpha-branched aldehydes and is catalyzed by a newly designed cinchona-derived primary amine catalyst.

At the onset the authors hypothesized the mechanism shown below.

The alpha-branched aldehyde (such as hydratropaldehyde (1a)) undergoes racemization in the presence of an aminocatalyst such as proline, through an equilibrium between an iminium ion and an enamine. An enantioselective reaction might be the performed by using the hypothetical difference of reactivity of the intermediary diastereomeric iminium ions A or Mannich products B, to give the Knoevenagek adduct.

Indeed, the authors found that proline is able to catalyze the reaction of aldehyde 1a with diethyl malonate to afford the corresponding Knoevenagle adduct, bu only with moderate enantioselectivity. Moreover, the formation in big amount of the byproduct  5 made the situation even more complicate.

A broader  screening of organocatalyst have been made by the author, in order to come up with good enantioselectivity and to reduce the formation of byproduct 5. In the scheme below the catalyst which have been tested are shown.

 

The catalyst J, with R=OMe, turned out to be the best one in terms of enantioselectivity, even if still a significant amount of byproduct 5 was formed. Therefore, using a large excess of malonate (50 equivalents) resulted in a big enhancement of enantioselectivity and formation of the byproduct only in slight amount.

In conclusion, List’s group has developed the first catalytic asymmetric Knoevenagel condensation. Racemic a-branched aldehydes can be converted in a dynamic kinetic resolution into the corresponding enantiomerically enriched products with enantiomeric ratios of up to >95:5.

 

 

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