Current Organic Synthesis - Volume 10, Issue 6, 2013

The present review summarizes the synthetic application of trichloroisocyanuric acid [1,3,5-trichloro-1,3,5-triazine-2,4,6- (1H,3H,5H)-trione] as a convenient reagent for the electrophilic chlorination of unsaturated carbon-carbon bonds and focuses on its green aspects. Chlorination reactions involving alkenes, alkynes, arenes, and (di)carbonyl compounds and the chlorodecarboxylation of cinnamic acids (Hunsdiecker reaction) are presented and discussed. Trichloroisocyanuric acid is a safe, stable, easily handled, inexpensive and commercially available solid. At the end of the reactions, cyanuric acid is obtained as by-product and can be reused to produce trichloroisocyanuric acid. In accordance with green chemistry principles, the use of trichloroisocyanuric acid enables chlorination without chlorine or other harmful or dangerous reagents.

It is difficult to imagine organic chemistry without organo-halogen compounds and the molecular halogens needed for their preparation. In fact, It is implied that halogenation of organic compounds is a key industrial process; for example, the halogenated products are used in the synthesis of many pesticides and pharmaceuticals. Conventional halogenation methods typically use pollutant, toxic and corrosive elemental halogens (X2), which also generate hydrohalic acid as byproduct and effectively reduce the atom efficiency. Hence, to avoid their use, various modified reagents (N-halo reagents such as trichloisocyanuric acid, haloglycolurils, N-halosuccinimid and …), methods such as oxidative halogenation in the presence of alkali halogen salts, biohalogenations, solid phase and ionic liquid have been developed. In this review article, we will focus on strategies that are much greener and more sustainable than those using elemental halogens.

The review highlights applications of bromide-bromate couple in organic synthesis. The couple having 5:1 mole ratio of bromide to bromate is useful for preparation of dibromo derivatives from alkenes/alkynes. The 2:1 couple affects substitution with high bromine atom efficiency. Vicinal functionalization of olefins has also been studied. The 1:8 bromide-bromate couple has proved promising in several oxidation reactions, the performance exceeding that of bromate alone. This reagent was also the most effective for deiodination of styrene-based iodohydrins with concomitant rearrangement by a novel pathway. In all the cases the reagents were activated through in situ acidification. The 5:1 reagent is obtained as intermediate during liquid bromine manufacture and the other reagents were prepared from it using ClO-. Liquid bromine could be avoided in the product life cycle.

1,3-Diol motif is of particular interest due to its prominence within many classes of natural products. In this field, β,δ-diketo sulfoxides are specially attractive because both syn- and anti-1,3-diols can be prepared from these key compounds by two successive high diastereoselective reductions of both carbonyls. Thus, β-carbonyl reduction requires DIBAL-H or the ZnX2/DIBAL-H system. The resulting stereochemistry of the corresponding hydroxyl is fully controlled by the chiral sulfoxide group. Then, the reduction of δ-carbonyl leads to syn or anti 1,3-diols depending on the hydride reagents employed and the stereoselectivity is directed by the newly formed β- hydroxylic center. In this paper, emphasis is given to the use of valuable β,δ-diketo sulfoxides in the total synthesis of selected natural products.

The present review compiles significant advances in different synthetic strategies to obtain various nucleoside triphosphates, which are indispensable materials for variety of important biological applications such as DNA sequencing, PCR, therapeutic nucleoside inhibitors of polymerase, to prepare apatamers by in vitro transcription methods, and ingredients in numerous biological assay kits. Modified nucleoside triphosphate analogs are increasingly evaluated as potential diagnostic and therapeutic agents as well as tools for reengineering DNA. This review covers literatures after the year 2000. The intent of this review is to summarize the most useful approaches that have been applied for nucleoside triphosphates syntheses with their advantages, limitations, and generality of methods. The present review will highlight most practical approaches to access nucleoside triphosphates and also research areas wherein further work might lead to superior and general approach. It will enable researchers to choose the right method for synthesizing their nucleoside triphosphates of interest by understanding pros and cons of many available methodologies. It will keep the researchers well informed of the state-of-the-art in the nucleoside triphosphate syntheses and the pressing needs.

Smiles rearrangement, an organic intramolecular nucleophilic aromatic substitution reaction, provides a powerful access to the synthesis of a variety of heterocyclic compounds. In contrast with the conventional protocols for the preparation of complex molecular structures, Smiles rearrangement, through the conversion of an easily-synthesized precursor into a desired “difficult-to-make’’ product, presents to be an extremely useful tool in organic synthesis. In the reactions, the yields of the Smiles rearrangement are profoundly influenced by electronic effect, steric effect and even the pH value. In this review, the detailed preparations of numerous molecules by taking advantage of Smiles rearrangement are discussed.

An unexpected three components reaction was developed for acridine synthesis in solvent free medium. The reaction is carried out with commercial reagents using of microwaves in a heterogeneous medium in presence of zinc chloride and 2,2-dimethoxypropane (DMP) as water scavenger. Principal advantages of the method are: short time, high yields and easy work-up.

1,2-Diaza-1,3-dienes bearing electron withdrawing groups react with α,β-unsaturated carbonyl compounds by means of an uncommon aza-Diels-Alder reaction furnishing functionalized tetrahydropyridazines. The regioselectivity of the process is governed by the nature of the β substituent of the α,β-unsaturated carbonyl compounds. In the case of β aryl-α,β-unsaturated carbonyl compounds the formed tetrahydropyridazines present the carbonyl group in a suitable position to undergo a further cyclization process that furnish new 2’-oxo-imidazo[1’,5’-f]tetrahydropyridazine derivatives.

A series of sulfides was successfully synthesized from nitroarenes by SNAr reaction via elimination of a nitro or phenylsulfonyl group. The SNAr reaction mechanism is found to depend on the position and type of substituents, and the effect of two-electron withdrawing groups was also examined.

An efficient preparation of the girgensohnine and its close analogs with α-aminonitrile structure, and their spectral characterization were reported for the first time. The piperidine α-aminonitriles were obtained through 5 mol% InCl3-catalyzed one-pot Strecker reaction, and tested for antioxidant activity and AChE inhibitory properties. It was found that girgensohnine possesses a moderate AChE inhibitory property while its spiroanalog shows good antioxidant capacity.

A novel and facile Biginelli-like assembly employing enaminones, aldehydes and 3-amino-1,2,4-triazole has been developed, which provides a novel synthesis of new 5-unsubstituted-6-aroyl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives.