Heteroaromatic N-Oxides Modified with a Chiral Oxazoline Moiety

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Interesting properties of N-oxides and pyridine oxazoline compounds have become the starting point to synthesize compounds connecting both groups. A multi-step synthesis of a series of chiral oxazoline substituted pyridine N-oxides, alkyl derived of pyridine N-oxides, bipyridine N-oxides, and isoquinoline N-oxides, based on amino alcohols derived from natural amino acids or other previously prepared, is presented herein. Various synthetic pathways have been designed and tested according to the properties and limitations imposed by the target products. The encountered problems related to the stability of the products were discussed. The resulting compounds (eighteen structures) were tested as catalysts in th e allylation of benzaldehyde (obtaining up to 79% ee) as well as in nitroaldol reaction (obtaining up to 48% ee).Get more news about Oxide Deoxidizing Catalyst,you can vist our website!
1. Introduction
An increasing interest in the development of the chemistry and applications of N-oxides has been observed in the last decade. Apart from the fact that azaaromatic N-oxides can be found in nature [1] and their biological activity is recognized, due to their unique properties being a consequence of the N-O moiety presence, they have found various applications. They can serve as oxidants [2], intermediates having significant synthetic value en route to diversely functionalized N-heterocycles, and in industrial syntheses of pharmaceuticals [3]. N-oxides are key components for ubiquitously used materials such as detergents, toilet soaps, toothpaste, shampoos, and cosmetics [4]. N-oxidation dramatically alters the reactivity of the parent base by activating the heteroaromatic ring towards both nucleophilic and electrophilic reagents
2. Results and Discussion
In general, heteroaromatic N-oxides have been easily obtained via oxidation of heterocycles. The procedure for the methyltrioxorhenium (MTO) mediated oxidation of pyridines was developed by Sharpless [18], but despite its simplicity and efficiency it has several limitations. Procedures using m-chloro-peroxy-benzoic acid (m-CPBA) in mild conditions seem to be more universal [19]. There are two general approaches to obtain an oxidized nitrogen atom in the designed bifunctional compounds, shown in Scheme 1. The first assumes oxidation before oxazoline ring closure (A), while the second consists of the oxidation of previously received heteroaromatic-oxazoline-type compounds (. The introduction of an oxazoline ring into the molecule can be accomplished by reacting the chiral amino alcohol with an oxidized or non-oxidized aromatic nitrile or carboximidate.
3. Materials and Methods
3.1. General
Solvents were distilled, and other reagents were used as received. Reactions were monitored by thin-layer chromatography (TLC) on silica gel 60 F-254 precoated plates (Merck, Darmstadt, Germany), and spots were visualized with a UV lamp. Products were purified by standard column chromatography on silica gel 60 (230–400 mesh) (Merck). Optical rotations at 578 nm were measured using an Optical Activity Ltd. (Huntington, UK) Model AA-5 automatic polarimeter. Melting points were determined using a Boëtius hotstage apparatus (PHMK VEB Analytic, Dresden, Germany). 1H and 13C NMR (400 MHz and 100 MHz, respectively) spectra were recorded in CDCl3 on Jeol 400yh and Bruker Avance II 600 instruments (Karlsruhe, Germany). High-resolution mass spectra (HRMS) were recorded using electrospray ionization mode on the Waters LCT Premier XE TOF spectrometer (Waters Corporation, Milford, MA, USA). The enantiomeric ratios of the samples were determined by chiral high-performance liquid chromatography (HPLC) measurements (Thermo Fisher Scientific, Waltham, MA, USA) using Chiracel OD-H, OB-H, or Chiralpak AS-H chiral columns. The configuration of the products was assigned by comparison to literature data. 1HNMR and 13C NMR spectra of all newly obtained compounds are shown in Supplementary Materials (Figure S1–S29).