资源环境科技发展态势分析平台

Multicomponent reactions are relied on in both academic and industrial synthetic organic chemistry owing to their step- and atom-economy advantages over traditional synthetic sequences(1). Recently, bicyclo[1.1.1]pentane (BCP) motifs have become valuable as pharmaceutical bioisosteres of benzene rings, and in particular 1,3-disubstituted BCP moieties have become widely adopted in medicinal chemistry as para-phenyl ring replacements(2). These structures are often generated from [1.1.1]propellane via opening of the internal C-C bond through the addition of either radicals or metal-based nucleophiles(3-13). The resulting propellane-addition adducts are then transformed to the requisite polysubstituted BCP compounds via a range of synthetic sequences that traditionally involve multiple chemical steps. Although this approach has been effective so far, a multicomponent reaction that enables single-step access to complex and diverse polysubstituted drug-like BCP products would be more time efficient compared to current stepwise approaches. Here we report a one-step three-component radical coupling of [1.1.1]propellane to afford diverse functionalized bicyclopentanes using various radical precursors and heteroatom nucleophiles via a metallaphotoredox catalysis protocol. This copper-mediated reaction operates on short timescales (five minutes to one hour) across multiple (more than ten) nucleophile classes and can accommodate a diverse array of radical precursors, including those that generate alkyl, alpha-acyl, trifluoromethyl and sulfonyl radicals. This method has been used to rapidly prepare BCP analogues of known pharmaceuticals, one of which is substantially more metabolically stable than its commercial progenitor.

A one-step, three-component radical coupling of [1.1.1]propellane by a photoredox reaction mediated by a copper catalyst produces drug-like bicyclopentanes.

A synthetic approach is described, for efficiently converting non-van der Waals solids into two-dimensional van der Waals transition-metal chalcogenide layers with specific phases, enabling the high-throughput production of monolayers.

Although two-dimensional (2D) atomic layers, such as transition-metal chalcogenides, have been widely synthesized using techniques such as exfoliation(1-3) and vapour-phase growth(4,5), it is still challenging to obtain phase-controlled 2D structures(6-8). Here we demonstrate an effective synthesis strategy via the progressive transformation of non-van der Waals (non-vdW) solids to 2D vdW transition-metal chalcogenide layers with identified 2H (trigonal prismatic)/1T (octahedral) phases. The transformation, achieved by exposing non-vdW solids to chalcogen vapours, can be controlled using the enthalpies and vapour pressures of the reaction products. Heteroatom-substituted (such as yttrium and phosphorus) transition-metal chalcogenides can also be synthesized in this way, thus enabling a generic synthesis approach to engineering phase-selected 2D transition-metal chalcogenide structures with good stability at high temperatures (up to 1,373 kelvin) and achieving high-throughput production of monolayers. We anticipate that these 2D transition-metal chalcogenides will have broad applications for electronics, catalysis and energy storage.