Amine-Free, Directing-Group-Free and Redox-Neutral α-Alkylation of Saturated Cyclic Ketones.

The activation of the α-C-H bond of ketones typically requires an amine and a directing group to guide the reaction selectivity in amine-catalysis carbonyl chemistry. For an α-C-H bond activation of ketone, directing groups are also required to control the reaction selectivity. Reported herein is the first α-alkylation of cyclic ketones in the absence of an amine catalyst and directing group. 1 H NMR, XPS, EPR studies and DFT calculations indicate that an α-carbon radical intermediate is formed through direct and selective activation of the inert α-C-H bond of ketones chelating on the surface of colloidal quantum dots (QDs). Such an interaction is essential for weakening the C-H bond, as exemplified, using CdSe QDs as the sole photocatalyst to execute α-C-H alkylation of cyclic ketones under visible-light irradiation. Without an amine catalyst and directing group, the high step- and atom-economy transformation under redox-neutral condition opens a new way for α-C-H functionalization of ketones in carbonyl chemistry.

Direct N-H Activation to Generate Nitrogen Radical for Arylamine Synthesis via Quantum Dots Photocatalysis.

Represented herein is the first example of N-radical generation direct from N-H bond activation under mild and redox-neutral conditions. The in situ generated N-radical intercepts a reduced heteroarylnitrile/aryl halide for C-N bond formation under visible-light irradiation of quantum dots (QDs). A series of aryl and alkylamines with heteroarylnitriles/aryl halides exhibit high efficiency, site-selectivity and good functional-group tolerance. Moreover, consecutive C-C and C-N bond formation using benzylamines as substrates is also achieved, producing N-aryl-1,2-diamines with H2 evolution. The redox-neutral conditions, broad substrate scope, and efficiency of N-radical formation are advantageous for organic synthesis.

Direct C(sp)-H/Si-H Cross-Coupling via Copper Salts Photocatalysis.

Reported herein is the first example of C(sp)-H/Si-H cross-coupling by photocatalysis. In terms of cheap and readily available starting materials, a series of alkynylsilanes are prepared in good to excellent yields upon visible-light irradiation of CuCl and alkynes with silane. The large scale reaction with flow chemistry and late-stage functionalization of natural products shows the potential of the transformation in practical organic synthesis of the alkynylsilanes intermediates.

Site-Selective N-1 and C-3 Heteroarylation of Indole with Heteroarylnitriles by Organocatalysis under Visible Light.

Site-selective N-1 and C-3 arylation of indole has been sought after because of the prevalent application of arylindoles and the intricate reactivities associated with the multiple sites of the N-unsubstituted indole. Represented herein is the first regioselective heteroarylation of indole via a radical-radical cross-coupling by visible-light irradiation. Steady and time-resolved spectroscopic and computational studies revealed that the hydrogen-bonding interaction of organic base and its conjugated acid, namely with indole and heteroarylnitrile, determined the reaction pathway, which underwent either proton-coupled electron-transfer or energy-transfer for the subsequent radical-radical cross-coupling, leading to the regioselective formation of C-3 and N-1 heteroarylation of indoles, respectively. The parallel methodologies for regioisomeric N-1 and C-3 heteroaryl indoles with good functional group compatibility could be applied to large-scale synthesis and late-stage derivatization of bioactive compounds under extremely mild reaction conditions.

Affinity ultrafiltration and UPLC-HR-Orbitrap-MS based screening of thrombin-targeted small molecules with anticoagulation activity from Poecilobdella manillensis.

This study aims to screen potential anticoagulant components from leeches, a representative animal-sourced traditional Chinese medicine using thrombin (THR)-targeted ultrafiltration combined with ultrahigh performance liquid chromatography and high-resolution Orbitrap mass spectrometry (UPLC-HR-Orbitrap-MS). As a result, five small molecules in leech extract were discovered to interact with THR for the first time. Among them, two new compounds were isolated and their structures were identified by IR, HR-MS and NMR data. Furthermore, their THR inhibitory activity was confirmed with IC50 values of 4.74 and 8.31 µM, respectively. In addition, molecular docking analysis showed that the active (catalytic) site of THR might be the possible binding site of the two hits. Finally, reverse screening analysis indicated that LTA4-H, ACE and ALOX5AP were potential anticoagulant targets of the two new compounds. This study will broaden our understanding of the medicinal substance basis in leeches and further contribute to the discovery and development of clinical anticoagulant drugs from leeches.

Photoredox Oxo-C(sp3)-H Bond Functionalization via in Situ Cu(I)-Acetylide Catalysis.

A unified strategy for the synthesis of 2-vinyl heterocycles is reported. With visible light irradiation, simple and cheap CuCl is able to functionalize a terminal alkyne, giving Cu(I)-acetylide in situ. Unlike the case of noble metals or organic dye photocatalysts, this critical Cu(I)-acetylide not only activates the C-H bond of terminal alkynes but also serves as a photocatalyst to achieve varieties of 2-vinyl heterocycles in good to excellent yields, even for large scale and late-stage functionalization of natural product.