Current Organic Synthesis - Volume 13, Issue 2, 2016

Tetrahydroquinoline (THQ) subunits are present in many natural products and biologically active agents, such as anti-viral, anti-biotic, and anti-tumour medications. The synthesis of THQs is described extensively in literature due to the search for a general, simple, efficient and low-cost preparation method. The retrosynthetic analysis for THQ synthesis has many strategies involving the formation of one or two C-C or C-N bonds. In 1963, Povarov et al. published two studies named “A new type of diene condensation reaction” and “Reaction of benzylideneaniline with some unsaturated compounds". These studies described a converging reaction for the formation of two C-C bonds. However, in addition to using easily available starting material, this route remained unexplored for thirty-two years as the result of a small product yield, the need of previous formation of the precursor imines, and the use of stoichiometric amounts of the catalyst. However, in 1995, Kobayashi et al. performed the one-pot multi-component version of the Povarov reaction among anilines, aldehydes and alkenes acting as dienophiles, and this reaction was catalysed by Lewis acids and resulted in reasonable yields. Thus, the Povarov reaction was reborn to researchers. Currently, the Povarov reaction is classified into three wellstudied categories as follows: i) the original one-pot ABC using aniline, aldehydes and activated alkenes; ii) the ACC' using anilines and two equivalents of dienophile; and iii) AA'BB' involving the use of two equivalents of aniline and two equivalents of enolisable aldehyde.

Organocatalysts are small organic molecules that accelerate a reaction when used in sub-stoichiometric amounts. Their utility in various synthetically useful transformations have increased enormously in the past decade. Representing a link between two major forms of catalysis: metal complex mediated catalysis and enzymatic catalysis, the term ‘organocatalysis’ establishes connectivity between synthetic and bioorganic chemistry. Despite the enormous utility and selectivity of organocatalysts, there are very few selected basic substrates which have proven to be potent scaffolds for organocatalyts. Carbohydrate moiety due to its ready availability, high functionality, several stereogenic centers and other fascinating structural aspects, provides accessibility for the synthesis of series of chiral ligands that are highly selective for particular reactions. Hence, chirality and functional diversity are the key features due to which sugar moiety might prove to be a potent scaffold for metal free catalysis. A number of stereospecific reactions can be accelerated by carbohydrate based chiral molecules. Due to these reasons carbohydrate moiety has recently emerged from relative obscurity to prominence as highly efficient substrates for the synthesis of organocatalysts which furnishes products with high enantioselectivity. This review highlights the basic aspects and recent impressive progress in the area of carbohydrate based organocatalysts as well as organo-catalytic reactions. The different carbohydrate based organocatalysts have been classified on the basis of their chemical structures and functionalities.

Pyridinium chlorochromate (PCC) is an important reagent in organic synthesis used primarily for the selective oxidation of alcohols to give carbonyl compounds. Although a variety of related compounds are known with similar reactivity, PCC offers exclusively the advantage of the selective oxidation of alcohols to aldehydes, whereas many other reagents were less selective. Disadvantages of using PCC are the tedious reaction workup and its toxicity, very well compensated by selective oxidation, observed using this reagent as an oxidant. This useful oxidant was first synthesized and used by E. J. Corey and J. William Suggs in 1972.

Advances in the application of aluminum-based metal alloys in the hydrogenation as well as deuteration of a broad range of organic compounds are reviewed. The use of the Al-based alloys allows, and in fact favors, the reaction to be carried out in aqueous medium, which is a major step forward for reduction reactions given the recent need for environmentally benign reaction design. The Al content of the alloy, used as reductant, reacts with water in situ providing hydrogen and a Raney-type catalyst, thus the alloy serves as both a hydrogen generator as well as a hydrogenation catalyst. The applications can easily be extended to the preparation of isotope labeled materials by the simple use of D2O. The simpilicity and efficacy of the method is illustrated by the reduction of a variety of compound groups including carbonyl compounds, aromatic and heteroaromatic rings, aryl halides, phenols, nitriles, nitroso or nitro compounds, just to name a few. The work includes three chapters; (i) the major types of commercially available Al-based alloys and their basic characteristics and condition for their use, (ii) the discussion of recent results related to the hydrogenation of major functional group types and finally (iii) the application of these alloys in the preparation of deuterium labeled compounds.

A unified convergent strategy has been developed for the facile synthesis of a series of novel fused azines bearing a phenothiazine moiety based on the aza-Michael addition reaction of an enaminone derivative to a variety of different heterocyclic amines under microwave irradiation conditions. The results of this study revealed that new methods are required to allow for the simple and efficient analysis of the fused azine products of this reaction other than single-crystal X-ray crystallography. With this in mind, 1H–15N HMBC experiments were used in the current study to allow for the unambiguous structural characterization of the fused azine products. These results provided further support in favor of the proposed structures and allowed for the resolution of several discrepancies reported in the literature regarding the structural characterization of these compounds.

A series of novel cyclohepta[1,2-d][1,2,4]triazolo[4,3-a]pyrimidines was prepared by reaction of 9- arylmethylene-cycloheptapyrimidine-2-thione with hydrazonoyl halides in dioxane in the presence of triethylamine. Also, a series of fused cycloheptapyrimidines was synthesized via reaction of 2,7-diarylmethylenecycloheptanone with heterocyclic amines. The products 14a-c of the latter reaction were used as starting materials since they contain an olefinic exocyclic C=C and endocyclic C=N bonds. 1,3-Dipolar cycloaddition reaction of these products with hydrazonoyl halides in benzene in the presence of triethylamine afforded novel spiropyrazolines. All the above reactions proceeded site and regio-selectively, and the structures of the products were established based on both elemental and spectral analysis data (IR, 1H NMR, MS). In addition, the biological activity of some of the new products was evaluated and the results obtained revealed medium to high activity against some bacteria and fungi species.

A new aci-quinone compound, 4-(aci-nitro)-2-(methoxy)-5-(3-nitro-2-(nitrooxy)propyl)-cyclohexa-2,5- dienone (2), an analog to 4-(aci-nitro)-2-(carboxymethoxy)-5-(3-nitro-2-(nitrooxy)propyl)-cyclohexa-2,5-dienone (1), was successfully synthesized and fully characterized by spectroscopic methods. The reactions of 1 and 2 with various reagents such as hydroxylamine, acetic anhydride, semicarbazide and thiosemicarbazide were examined. The structure of 11 obtained new compounds was established by IR, 1H NMR, 13C NMR, HMBC and MS spectra. It was shown that the unstable, sensitive aci-quinone structure of compounds 1 and 2 can exist in anhydrous organic solvents such as AcOEt, EtOH but in the presence of water, H+, HO- or at high temperatures, the aci-quinone structure of both 1 and 2 tendentiously transformed into the more stable nitro-phenol form.