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Abstract We report a highly enantioselective intermolecular C−H bond silylation catalyzed by a phosphoramidite‐ligated iridium catalyst. Under reagent‐controlled protocols, propargylsilanes resulting from C(sp³)−H functionalization, as well the regioisomeric and synthetically versatile allenylsilanes, could be obtained with excellent levels of enantioselectivity and good to excellent control of propargyl/allenyl selectivity. In the case of unsymmetrical dialkyl acetylenes, good to excellent selectivity for functionalization at the less‐hindered site was also observed. A variety of electrophilic silyl sources (R₃SiOTf and R₃SiNTf₂), either commercial or in situ‐generated, were used as the silylation reagents, and a broad range of simple and functionalized alkynes, including aryl alkyl acetylenes, dialkyl acetylenes, 1,3‐enynes, and drug derivatives were successfully employed as substrates. Detailed mechanistic experiments and DFT calculations suggest that an η³‐propargyl/allenyl Ir intermediate is generated upon π‐complexation‐assisted deprotonation and undergoes outer‐sphere attack by the electrophilic silylating reagent to give propargylic silanes, with the latter step identified as the enantiodetermining step. 

Abstract Methods that can simultaneously install multiple different functional groups to heteroarenes via C−H functionalizations are valuable for complex molecule synthesis, which, however, remain challenging to realize. Here we report the development of vicinal di‐carbo‐functionalization of indoles in a site‐ and regioselective manner, enabled by the palladium/norbornene (Pd/NBE) cooperative catalysis. The reaction is initiated by the Pd(II)‐mediated C3‐metalation and specifically promoted by the C1‐substituted NBEs. The mild, scalable, and robust reaction conditions allow for a good substrate scope and excellent functional group tolerance. The resulting C2‐arylated C3‐alkenylated indoles can be converted to diverse synthetically useful scaffolds. The combined experimental and computational mechanistic study reveals the unique role of the C1‐substituted NBE in accelerating the turnover‐limiting oxidative addition step. 

Due to the scarcity of C–F bond-forming enzymatic reactions in nature and the contrasting prevalence of organofluorine moieties in bioactive compounds, developing biocatalytic fluorination reactions represents a pre-eminent challenge in enzymology, biocatalysis and synthetic biology. Additionally, catalytic enantioselective C(sp3)–H fluorination remains a challenging problem facing synthetic chemists. Although many non-haem iron halogenases have been discovered to promote C(sp3)–H halogenation reactions, efforts to convert these iron halogenases to fluorinases have remained unsuccessful. Here we report the development of an enantioselective C(sp3)–H fluorination reaction, catalysed by a plant-derived non-haem enzyme 1-aminocyclopropane-1-carboxylic acid oxidase (ACCO), which is repurposed for radical rebound fluorination. Directed evolution afforded a C(sp3)–H fluorinating enzyme ACCOCHF displaying 200-fold higher activity, substantially improved chemoselectivity and excellent enantioselectivity, converting a range of substrates into enantioenriched organofluorine products. Notably, almost all the beneficial mutations were found to be distal to the iron centre, underscoring the importance of substrate tunnel engineering in non-haem iron biocatalysis. Computational studies reveal that the radical rebound step with the Fe(III)–F intermediate has a low activation barrier of 3.4 kcal mol−1 and is kinetically facile. 

Herein we disclosed an unprecedented photochemically driven nickel‐catalyzed carboxylative Buchwald–Hartwig amination to access a wide range of aryl carbamate derivatives. This reaction is performed under mild condition of temperature and atmospheric pressure of CO2 starting from commercially available (hetero)aryl iodides/bromides derivatives and alkyl amines preventing the formation of hazardous and/or toxic waste. Moreover, preliminary mechanistic investigations including stochiometric experiments as well as DFT calculations allow us to shed light on the reaction mechanism.