Current Organocatalysis - Volume 3, Issue 2, 2016

Organocatalytic reactions are now becoming powerful tools in the construction of simple to complex molecular skeletons and this field is growing rapidly with new concepts and designs. During the recent past, sulfamic acid (NH2SO3H) has emerged as an efficient organocatalyst in the formation of both carbon-carbon and carbon-heteroatom bonds, thereby resulting different classes of organic compounds of potential interest. Sulfamic acid is commercially readily available, inexpensive and highly stable, and finds applications as an organocatalyst in organic chemistry. It can catalyze a variety of organic transformations such as many named reactions, protection of different functional groups, one-pot multi-component reactions, condensations, oxidations, ring openings, and the synthesis of various pharmaceutically important heterocyclic compounds. The present review summarizes the latest developments on sulfamic acid-catalyzed organic transformations reported during the last decade with a focus on carbon-carbon and carbonheteroatom bond forming reactions among others.

A simple, straightforward and eco-friendly protocol for the synthesis of pharmaceuticallyinteresting aryl/heteroaryl-substituted bis(6-aminouracil-5-yl)methane derivatives has been developed using sulfamic acid (NH2SO3H) as a cost-effective and non-toxic organo-catalyst via pseudomulticomponent reaction of 6-amino-1,3-dimethyluracil with aromatic/heteroaromatic aldehydes in aqueous ethanol at room temperature. Mild reaction conditions, good to excellent yields, ecofriendliness, easy isolation of products and avoidance of column chromatographic separation are some of the notable features of this protocol.

Considerable number of nitrogen containing active pharmaceutical ingredients and natural products are frequently synthesized from optically pure β-amino ketones, aldehydes, esters, and alcohols. Synthesis of 1,3-amino ketones, aldehydes, alcohols and esters engages Mannich-type reactions, the most important basic reaction-types in organic chemistry. The current trend in the development of asymmetric Mannich-type reaction is to employ unmodified ketones and aldehydes as starting materials in the presence of simple and easily accessible metal-free organocatalysts under mild and convenient reaction conditions. Although L-Proline and its derivatives are commonly and extensively studied organocatalysts in Mannich reactions, many other organocatalysts based on bifunctional thiourea, chiral Bronsted acids and some other organocatalytic systems are also equally effective. The present review comprehensively describes an overview of asymmetric Mannich reactions under different organocatalytic systems in both organic and aqueous media.

Cellulose nanoribbons obtained from bacterial fermentation have been esterified by means of a solventless organocatalytic route. The esterification methodology involves acetic anhydride as acylant and three different α-hydroxy acids were tested as organocatalysts. By tuning the acetylation interval, bacterial nanocellulose (BNC) with varying degree of substitution could be obtained (i.e. DS=0.27-0.90). Esterified BNC has been characterized in terms of its morphology, chemical structure, crystallinity, wettability and dispersibility in different solvents. The results indicate the efficacy of the present methodology for the smooth acetylation of cellulose nanoribbons at moderate conditions, thereby expanding the role of organocatalysts in reducing the hydrophilicity of bacterial cellulose nanoribbons.

An efficient, simple and environmentally benign methodology has been developed for the synthesis of 5,6-unsubstituted 1,4-dihydropyridine derivatives by a three-component condensation of β-keto esters, amines and α,β-unsaturated aldehydes under solvent-free conditions catalyzed by an aprotic imidazole-based zwitterionic salt. The key advantages of this protocol are metal-free reaction conditions, short reaction time, high yields, reusability of the catalyst, and easy work-up. A variety of dihydropyridine derivatives have been synthesized with high yields at room temperature and only water is formed as a green by-product.

The multicomponent reactions involving the use of environmentally benign solvents, and non-toxic, and recyclable organocatalysts require special attention as with such significant characters, the multicomponent reactions satisfy the green chemistry’s principles to a greater extent. The environmentally benign synthetic protocols with the amalgamation of multicomponent reactions, characterized by synthetic efficiency and structural diversity with bio-relevance offered by natural products, facilitate the generation of high quality leads for drug discovery. In the present review, the significant research work relating to the L-proline catalyzed multicomponent reactions has been presented. Moreover, the reactions catalyzed by tagged L-proline or modified L-proline based organocatalysts have also been included with a view to incorporate recent research trends in L-proline organocatalysis.

This is the first report on the organocatalytic activity of simple unsubstituted p-tertbutylcalix[ 8]arene, C8 towards multi-ring heterocycles. We thereby account an expeditious, ecofriendly, high throughput procedure of the synthesis of some biologically active cores xanthenes and acridines along with spiro-derivatives of both with the aid of the organocatalyst C8. The catalyst is recyclable for at least six cycles without substantial loss of activity.

A DBU-catalyzed one-pot multicomponent reaction involving indane-1,3-dione, aldehydes, and 1,4-dithiane-2,5-diol for the synthesis of spirocyclic tetrahydrothiophene derivatives has been developed. A series of spirocyclic tetrahydrothiophene derivatives were obtained in generally good to excellent yields with high diastereoselectivity via this synthetic strategy. Importantly, this methodology has several advantages, such as mild reaction conditions, broad scope of substrates, easy operations and so on.