Current Organic Chemistry - Volume 13, Issue 18, 2009

After nearly 20 years of extensive study and rapid development, multicomponent reactions have already been an commonly used and powerful tool for the construction of novel and complex target molecules. Up to now, numerous literatures on the development of novel MCRs have been reported and several reviews have summarized the progress on MCRs before the end of 2005 thoroughly. Recently, with the development of new methodologies of organic synthesis, MCRs have penetrated into various aspects of organic synthesis. This special thematic issue includes five reviews which devote to the research on multicomponent reaction of the specific compound classes, new catalysts and the most commonly used green reaction media, respectively. The first review, written by E. J. Yoo and S. Chang, Department of Chemistry, Korea Advanced Institute of Science and Technology, focuses on authors' and other groups' recent progresss on the new type of Cu-catalyzed multicomponent reactions which have been developed relying on the in situ generation of N-sulfonyl- or N-phosphorylketenimine intermediates. They comprehensively summarize this facile and versatile route to ketenimines which has led to the development of a range of highly efficient multicomponent reactions by employing diverse nucleophiles such as amines, alcohols, water, pyrroles, and thiolates. Alkynones are versatile three-carbon building blocks in heterocyclic chemistry and are easily prepared by a modified Sonogashira coupling of acid chlorides and terminal alkynes. The second review provided by B. Willy and T. J. J. Muller, Institute of Organic Chemistry and Makromolecular Chemistry, Heinrich-Heine University, is dedicated to their achievements in multicomponent synthesis of heterocycles initiated by Pd-catalyzed generation of alkynones as established (by themselves) within the past years. Thus, isoxazoles, indolizines, pyrazoles, pyridimines, 1,5-benzoheteroazepines, furans, oxazoles and pyrroles are readily accessible by this novel multicomponent reactions under the mild reaction conditions. P. J. Tambade, Y. P. Patil and B. M. Bhanage, Department of Chemistry, Institute of Chemical Technology (Autonomous), contribute to the third review, including more than 84 references, which deals with recent development in the fields of multicomponent reactions catalyzed by lanthanides. Some named reactions such as Biginelli, Hantzsch, Ugi, Mannich, and Povarov reaction catalyzed by various lanthanides are dicussed. The combination of water as an environmentally benign solvent for chemical transformations with multicomponent reactions has been receiving much attention. K. Kumaravel and G. Vasuki, Department of Chemistry, Pondicherry University, make a thorough literature survey of multicomponent reactions performed in water or aqueous solutions, are including nearly 108 references.

A new type of Cu-catalyzed multicomponent reaction has been developed relying on the in situ generation of N-sulfonyl- or N-phosphorylketenimine intermediates, which are obtained from the cycloaddition of 1-alkynes and sulfonyl- or phosphoryl azides followed by ring-opening rearrangement of the initially formed copper triazole species. This facile and versatile route to ketenimines has led to develop a range of highly efficient multicomponent reactions by employing diverse nucleophiles such as amines, alcohols, water, pyrroles, and thiolates. Additionally, intramolecular version and cycloadditions of the ketenimines with imines or their derivatives have also been developed on the basis of the same strategy. (This article is dedicated to Professor Bong Rae Cho of Korea University on the occasion of his 60th birthday).

Alkynones are versatile three-carbon building blocks in heterocyclic chemistry. They are easily and efficiently prepared by a modified Sonogashira coupling of acid chlorides and terminal alkynes. As a consequence of the mild reaction conditions the stage is set for new diversity-oriented routes to heterocycles by sequential and consecutive transformations. Hence, isoxazoles, indolizines, pyrazoles, pyridimines, 1,5-benzoheteroazepines, furans, oxazoles, pyrroles, tetrahydro- β-carbolines, 4H-thiochromen-4-ones and 4H-thiopyrano[2,3-b]pyridin-4-ones are readily accessible by multicomponent coupling-cycloaddition, coupling-addition-cyclocondensation, or coupling-addition-substitution reactions in a one-pot fashion.

Fluorinated compounds play a unique role in the development of novel lead compounds in both medicinal chemistry and modern crop protection. The introduction of fluorine atom always produces significant changes in the physical properties and often improves the biological activity of target moleculars. Multicomponent reactions (MCRs) are becoming a vastly more powerful tool for the creation of molecule libraries due to their highly convergent diversity, efficiency, selectivity, and atom economy. This paper reviewed growing applications of the trifluoromethyl, difluoromethyl, and fluoroalkyl building blocks as one of components in the multicomponent reactions for the construction of complex and diverse fluorinated molecules, respectively.

This review covers some important developments in the field of multicomponent reactions catalyzed by lanthanides. Various aspects of well known multicomponent reactions such as Biginelli, Hantzsch synthesis, Ugi reaction, Mannich reaction, Povarov reaction, Kabachnik-Fields reaction and other reactions catalyzed by various lanthanides, role of catalyst, its recyclability, and reaction conditions were discussed in detail.

Multi-component reactions (MCR) performed in water or aqueous medium are surveyed in this review. Several named and new MCR which are mechanistically different have been successfully performed in water or aqueous medium creating diverse molecular skeletons. This protocol couples the benefits of MCR with that of water as solvent for organic transformations, thus facilitating efficient chemical production in environmentally benign way.

The considerable biological and medicinal activities of purine nucleoside derivatives have simulated the recent interest in the synthesis of some new purine nucleosides. The present work described the reaction of inosine (1) with triphenylphosphine which led to the formation of 5'-chloro-5'-deoxy inosine (2), which on reaction with methylamine and morphorine afforded the compounds (3) and (4) respectively. The benzoylation of inosine (1) with benzoylchloride led to the formation of 1-benzoyl inosine (5) followed by reaction with sodium hydroxide affording compound (6). While the treatement of inosine (1) with dichlorodimethylsilane gave the compound (7), which on reaction with ethylacrylate gave 1-etheoxycarbonylethyl-3, 5-O-(di-methylsilanediyl) ether inosine (8). Treatment of inosine (1) with methane sulfonylchloride led to the formation 3',5'-dimethanesulfonylinosine (9) which reacted with bormine to give 8-bromo-3',5'- dimethanesulfonylinosine (10) was allowed to react with thiourea to give 8-mercapto -3',5'-dimehanesulfonylinosine (11). The biological activities of the prepared compounds were also described.

Ethyl-4-thienyl-6-phenyl-2-oxo-1,2,3,4-tetrahydropyrimidine carboxyl ate (4) was obtained by the reaction of thiophene-2-carbaldehyde, urea and ethylbenzoylacetate. Reaction of (4) with phosphorous oxy chloride followed by hydrazine hydrate afforded the hydrazide (6), condensation of (6) with D-glucose followed by acetylation gave the acetylated compound (8), which cyclized into triazolopyrimidine derivatives (9) in presence of bromine/acetic acid the deprotection of compound (9) in presence of TEA/MeOH afforded the deprotected compound (10). Selected members of the compounds were screened for antimicrobial activity.