Metal-free direct C-6-H alkylation of purines and purine nucleosides enabled by oxidative homolysis of 4-alkyl-1,4-dihydropyridines at room temperature.

Herein we report the application of 4-alkyl-1,4-dihydropyridines (DHPs), which are easily prepared from inexpensive aldehydes in one step, for the direct site-specific C-H alkylation of purines and purine nucleosides. Despite there being three active C(sp2)-H bonds (C-2-H, C-6-H, and C-8-H) in the structure, the reactions still show high regioselectivity at the purinyl C-6-H position. Importantly, the reactions successfully avoid the use of transition metal catalysts and additional acids. Meanwhile, the protocols are not sensitive to moisture and require only persulfate as an oxidant. Besides, this method displays broad functional group compatibility and is easy to scale up. Notably, pharmaceutical purines, e.g. the natural product 6-hydroxymethyl nebularine isolated from basidiomycetes, can be smoothly prepared using this protocol.

Regiospecificity C(sp2)-C(sp3) Bond Construction between Purines and Alkenes to Synthesize C6-Alkylpurines and Purine Nucleosides Using O2 as the Oxidant.

A highly site-selective and Markovnikov-type radical C6-H alkylation of purines with alkenes is achieved, allowing fast construction of the C(sp2)-C(sp3) bond at the C-6-position of purines and purine nucleosides using O2 as a green oxidant and alkenes as cheap alkylation reagents. The route was also a radical route to synthesize C6-alkyl-N7-substituted purines with potential steric hindrance between C6-alkyl groups and N7-substituted groups. This reaction is easily scaled up and has excellent functional group compatibility and broad substrate scopes. Moreover, the unstable intermediate was also separated, which was the key evidence for the reaction mechanism.

Gold-Catalyzed Cyclization/Hydroboration of 1,6-Enynes: Synthesis of Bicyclo[3.1.0]hexane Boranes.

The gold-catalyzed cyclization/hydroboration of 1,6-enynes offers facile, versatile, and atom-economical one-step access to bicyclo[3.1.0]hexane boranes. This new protocol proceeds in moderate to good yields under mild conditions. Different from bicyclo[3.1.0]hexane borates, these products are stable in air and during chromatography. Moreover, the borane moiety of the products can readily undergo a diverse array of transformations. The kinetic isotope effect experiment indicates that the hydrogen-transfer step is a fast process, which is not involved in the rate-limiting step.

Regioselective C6-H Hydroxyalkylation of Purines and Purine Nucleosides via α-C-H Functionalization of Alcohols at Room Temperature.

The highly regioselective C6-H hydroxylalkylation of purines and purine nucleosides within 10 min via the α-C(sp3)-H functionalization of alcohols at room temperature is reported here for the first time. The reaction tolerated various functional groups, which have the potential for further modification to afford other valuable molecules. The reported method avoids metal catalysts, light, and protecting groups, giving a direct strategy to access 6-substitued alkylated purines and nucleosides with pharmaceutical bioactivities.

Copper(I)-catalyzed tandem synthesis of 2-acylquinolines from 2-ethynylanilines and glyoxals.

An efficient one-step synthesis of 2-acylquinolines using a copper-catalyzed tandem reaction of 2-ethynylanilines with glyoxals in the presence of piperidine has been developed. This new protocol successfully avoids multi-step operation and the use of highly toxic cyanides required in traditional methods, and provides a practical tool for synthetic and pharmaceutical chemists. Various 2-acylquinolines are obtained with perfect regioselectivity in moderate to good yields (up to 86%). The potential synthetic utility of this method is exemplified by a large-scale experiment and synthetic transformation of the products.

One-step synthesis of mixed valence FeOX nanoparticles supported on biomass activated carbon for degradation of bisphenol A by activating peroxydisulfate.

A novel FeOX nanoparticles supported biomass activated carbon (BAC/FeOX) composite was prepared through one-pot calcination method with FeCl3 and cherry stone powder as precursors. The carbonization of biomass, reduction of Fe3+, and FeOX anchored on carbon substrate could be achieved at the same time. Characterization with transmission electron microscope (TEM) and scanning electron microscope indicated that nanoscale FeOX distributed uniformly on carbon substrate, and X-ray photoelectron spectroscopy, X-ray diffraction, and high resolution TEM characterization proved that the loaded FeOX was high crystallinity of Fe3O4 and α-Fe0. Bisphenol A (BPA) was used to investigate the degradation performance of BAC/FeOX activating peroxydisulfate (PDS). The ratio of raw materials affected degradation efficiency of BPA intensively through the content, valence state, and dispersibility of FeOX nanoparticles, and the optimal material could degrade 20 mg/L BPA completely in 5 min at 0.1 g/L in the presence of 1 g/L PDS. Free radical determination and quenching experiments indicated that both SO4•- and •OH were involved in BPA degradation. The degradation pathway was proposed based on the identification of degradation intermediates. The facile synthesis method, high activation efficiency, and low-cost and environmental friendly raw materials made the BAC/FeOX-50 an alternative catalyst for organic pollution water treatment.

Purinyl N(3)-Directed Palladium-Catalyzed C-H Alkoxylation of N(9)-Arylpurines: A Late-Stage Strategy to Synthesize N(9)-(ortho-Alkoxyl)arylpurines.

A palladium-catalyzed alkoxylation of N(9)-arylpurines with primary or secondary alcohols has been developed successfully, which is a rare C-H activation reaction of polynitrogenated purines and offers a late-stage strategy to synthesize N(9)-(ortho-alkoxyl)arylpurines. Although there are more than four nitrogen atoms present in the purine moiety, the reaction can be effectively conducted by sterically blocking the N(1) site for catalyst coordination and first employing the purinyl N(3) atom as a directing group.

Copper-Catalyzed Intramolecular Alkoxylation of Purine Nucleosides: One-Step Synthesis of 5'-O,8-Cyclopurine Nucleosides.

A novel copper-catalyzed intramolecular dehydrogenative alkoxylation of purine nucleosides has been developed successfully, providing the 5'-O,8-cyclopurine nucleosides in one-step with a yield up to 90%. The method, which utilized an inexpensive CuCl catalyst and a di-tert-butyl peroxide (DTBP) oxidant was suitable in a broad substrate scope and proceeded well even in gram scale.