Chemo- and Site-Selective Alkyl and Aryl Azide Reductions with Heterogeneous Nanoparticle Catalysts

Abstract

Site-selective modification of bioactive natural products is an effective approach to generating new leads for drug discovery. Herein, we show that heterogeneous nanoparticle catalysts enable site-selective monoreduction of polyazide substrates for the generation of aminoglycoside antibiotic derivatives. The nanoparticle catalysts are highly chemoselective for reduction of alkyl and aryl azides under mild conditions and in the presence of a variety of easily reduced functional groups. High regioselectivity for monoazide reduction is shown to favor reduction of the least sterically hindered azide. We hypothesize that the observed selectivity is derived from the greater ability of less-hindered azide groups to interact with the surface of the nanoparticle catalyst. These results are complementary to previous Staudinger reduction methods that report a preference for selective reduction of electronically activated azides.

Design, Synthesis, and the Biological Evaluation of a New Series of Acyclic 1,2,3‐Triazole Nucleosides

“…The starting 3‐azidopropanol 27 was prepared from 3‐chloropropanol in 90% yield according to the literature procedure . Reaction of 3‐azidopropanol 27 with benzyl bromide gave 28 in 80% yield . Initially, we considered the respective N 3 ‐benzoylated quinazoline‐2,4‐diones as convenient substrates for the preparation of N 3 ‐benzoyl‐ N 1 ‐propargylquinazoline‐2,4‐diones 30a (Scheme ).…”

“…3‐Azidopropan‐1‐ol 27 , (3‐azidopropoxy)methylbenzene 28 , N 1 ‐(prop‐2‐yn‐1‐yl)isatoic anhydride , and N 3 ‐benzoyl‐ N 1 ‐(prop‐2‐yn‐1‐yl)quinazoline‐2,4‐dione 30a were obtained according to the literature procedures.…”

Nickel Boride Catalyzed Reductions of Nitro Compounds and Azides: Nanocellulose-Supported Catalysts in Tandem Reactions

“…The developed procedure enlarges the portfolio of azidereduction protocols providing organic chemists with a practically-convenient method that is superior, or complementary, to already existing protocols present in literature to perform the azide to amine conversion via hydrogenation. 32,35,37,45 With the aim of designing a sustainable reaction, the catalyst loading was successfully lowered to 0.5 mol%, representing a substantial improvement on respect of already existing methodologies catalyzed by cheap and abundant transition metal. 36,37 The reaction system was proved to be general for both aliphatic and aromatic azide and a wide range of azides were tested in an attempt to highlight the limits of the reaction system as well as its functional-group tolerability.…”

“…These low catalyst loading represent an important improvement on respect of previously reported transition metal-catalyzed hydrogenation of azides. 34,35,36,37 A series of organic azides were evaluated with the optimized reduction protocol, aliphatic azides showed high conversions and were isolated as the corresponding carbamate after subsequent in situ Boc-protections (Table 2). The reaction resulted also suitable for less accessible azides, and indeed, both secondary and tertiary azides were converted into their reduced products in good yields (Table 2, entries 4 and 5).…”

A Highly Efficient Ga(OTf)3/KI-Catalysed Transformation of aryl azides to aryl amines using low catalyst loading

“…6 There are a variety of synthetic methods reported in the literature for the reduction of azides to their corresponding amines. [7][8][9][10][11][12][13][14][15][16][17] Although the available methods are generally valuable, some of them have limitations such as harsh reaction conditions, toxicity of reagents, poor chemoselectivity, high catalyst loading, and convenience. Thus, there is a continuous need to explore new methods that can overcome these drawbacks and effectively achieve this reductive transformation.…”