Current Organic Synthesis - Volume 13, Issue 5, 2016

Hydroxamic acids attracted much attention due to their ability to coordinate a range of transition metal ions. Siderophores can be highlighted due to their role as iron carriers in biological systems. This chelation ability joined to their occurrence in living organisms lead to their possible use as drugs. One of the most important pharmacological properties is their ability to inhibit enzymes, activity that can give them properties such as antiinflammatory and anti-cancer agents. Another important feature resulting from their ability to form stable chelates is their use as ligands in asymmetric synthesis. In this review, we will discuss the most recent published results covering the above mentioned aspects.

This review covers the recent advances in the synthesis of enantiomerically pure hydroxylamine’s employing nitrones as starting materials. Nucleophilic additions of organometallic reagents to nitrones are the most common way for introducing a hydroxyamino group into carbon skeletons with the concomitant formation of a new carbon-carbon bond. Addition of nucleophiles derived from enolates, cyanide or fluorinated derivatives allows the preparation of complex structures. Radical additions and, in particular samarium diiodidemediated reductive coupling of nitrones with carbonyl compounds and α,β-unsaturated esters have also been considered. All these approaches provide efficient methods of preparation of enantiomerically pure hydroxylamine’s that are valuable synthetic intermediates.

The formation of C-C and C-X bonds is a fundamental process in synthesis. In recent years organocatalysis has become a powerful tool to achieve these steps in a highly stereoselective manner and the nitro-Michael reaction was frequently used. From the functionalization of simple aldehydes, ketones or dicarbonyl compounds to the synthesis of privileged heterocyclic structures often found present in naturally occurring bioactive compounds and pharmaceuticals, several developments are being continuously documented. This review is focused on the period Jan 2014-Mar 2015 and it highlights the novel prospects for targetoriented synthesis, including many novel domino and cascade processes initiated by nitro-Michael reactions.

This review is focused on the synthesis of isoxazolidines as the core of biologically active compounds having anti-cancer, antiviral, antibacterial and anti-inflammatory properties. The isoxazolidine ring, as mimetic of ribose, has been principally synthesized with high regio-, stereo- and enantioselectivity, applying the methodology of 1,3-dipolar cycloaddition, involving nitrones and alkenes as dipoles and dipolarophiles, respectively. The easy accessibility of this ring by this approach, then, makes this heterocycle, particularly suitable for the synthesis of small molecules useful in the design of new and modified drugs.

The substrate of the classical Claisen rearrangement is ether containing double bonds in α and β positions. Both double bonds can belong to the aromatic system. There are about half a dozen known rearrangements in which one or more carbon atoms of the starting allyl vinyl ether were replaced with hetero-atoms such as sulfur, nitrogen or phosphorus. Such processes can be considered versions of the Claisen rearrangement. It seemed worthwhile to determine which of the possible versions can offer valuable products or useful alternatives to existing synthetic methods. Surprisingly, the literature data are very scarce. The article looks into plausible rearrangements of 3-oxa-1,5-hexadienes in which one or more carbon atoms were replaced with atoms different than carbon. We call these reactions heterooxa-Claisen-rearrangements (HOCR). Particularly interesting are processes forming: • A new bond between an aromatic ring and a hetero-atom, • A sequence containing several (various) hetero-atoms, • Aliphatic α-amino, α-thio and α-hydroxy-carbonyl compounds. It is worth noting that (like in the classical Claisen rearrangement) the driving force for many of the described processes is the formation of the thermodynamically stable carbonyl (or P=O) group. Additionally, transition state optimizations for selected example reactions show similar gas phase activation energies to known Claisen rearrangements, indicating their plausibility in the laboratory.

Five new unsymmetrically substituted salts containing a benzimidazole backbone were synthesized in high yields and their structures were verified via spectroscopic and analytical methods such as HRMS, 1D and 2D NMR spectroscopy, FT-IR and elemental analysis. The catalytic properties of all the synthesized salts were tested in a homogeneous Suzuki-Miyaura cross-coupling reaction to get coupling products in high efficiencies with low amounts of in situ formed catalysts. In this reaction, the couplings of boronic acid derivatives with different aryl chlorides were made in the presence of palladium acetate, 2-6 and base at various times and temperatures. According to the obtained results, the benzimidazolium salts which are N-heterocyclic carbene (NHC) ligand precursors were found to have high catalytic activity. In particular, the coupling of 4-chlorotoluene with phenylboronic acid was obtained in very high yield and conversion in the catalyzed Pd-NHC complexes which were in situ formed from compounds 3 and 6 and Pd(OAc)2.

Some acidic functionalized ionic liquids were evaluated for catalytic properties in synthetic reaction of peracetylated thiosemicarbazones having D-glucose moiety. For the first time, the ionic liquid, namely, 2-hydroxyethylammonium acetate proved to be an efficient, environment-friendly and easy catalyst for synthesis of these thiosemicarbazones in water as solvent under microwave irradiation, with high yields. The greener feature was found to be fairly general and the aqueous reaction media was reused in subsequent reactions with consistent activity. A series of N-(tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazones of substituted acetophenones and benzaldehydes have been synthesized based on these investigated results.

The coumarin derivatives have the anabolic, antioxidant, hepatoprotective, anticoagulant, HIV-proteases’ inhibitory, CNS depressant, hypnotics, sedative, diuretic, analgesic and antitubercular activities. In the present study, the synthesis of some 4-methylcoumarin derivatives in appreciably good yields has been achieved by the photo-irradiation of th e 2-methyl-3-(prop-2-ynyloxy)-4H-chromen-4-ones with pyrex filtered UV-light from 125W Hg lamp. The reaction is unprecedented and proceeded under mild and eco-friendly conditions within 60 minutes and may become an important tool for obtaining the 4-methylcoumarin derivatives.