Project description:Aziridines are important structural motifs and intermediates, and several synthetic strategies for the direct aziridination of alkenes have been introduced. However, many of these strategies require an excess of activated alkene, suffer from competing side-reactions, have limited functional group tolerance, or involve precious transition metal-based catalysts. Herein, we demonstrate the direct aziridination of alkenes by combining sulfonyl azides as a triplet nitrene source with a catalytic amount of an organic dye functioning as photosensitizer. We show how the nature of the sulfonyl azide, in combination with the triplet-excited state energy of the photosensitizer, affects the aziridination yield and provide a mechanistic rationale to account for the observed dependence of the reaction yield on the nature of the organic dye and sulfonyl azide reagents. The optimized reaction conditions enable the aziridination of structurally diverse and complex alkenes, carrying various functional groups, with the alkene as the limiting reagent.
Project description:Herein, a metal-free electrochemical dihydroxylation of unactivated alkenes is described. The transformation proceeds smoothly under mild conditions with a broad range of unactivated alkenes, providing valuable and versatile dihydroxylated products in moderate to good yields without the addition of costly transition metals and stoichiometric amounts of chemical oxidants. Moreover, this method can be applied to a range of natural products and pharmaceutical derivatives, further demonstrating its synthetic utility. Mechanistic studies have revealed that iodohydrin and epoxide intermediate are formed during the reaction process.
Project description:Chiral aziridines are important structural motifs found in natural products and various target molecules. They serve as versatile building blocks for the synthesis of chiral amines. While advances in catalyst design have enabled robust methods for enantioselective aziridination of activated olefins, simple and abundant alkyl-substituted olefins pose a significant challenge. In this work, we introduce a novel approach utilizing a planar chiral rhodium indenyl catalyst to facilitate the enantioselective aziridination of unactivated alkenes. This transformation exhibits a remarkable degree of functional group tolerance and displays excellent chemoselectivity favoring unactivated alkenes over their activated counterparts, delivering a wide range of enantioenriched high-value chiral aziridines. Computational studies unveil a stepwise aziridination mechanism in which alkene migratory insertion plays a central role. This process results in the formation of a strained four-membered metallacycle and serves as both the enantio- and rate-determining steps in the overall reaction.
Project description:Transition metal-catalyzed cross-coupling reaction between organometallic reagents and electrophiles is a potent method for constructing C(sp2)-C(sp3) bonds. Given the characters of organometallic reagents, cross-reductive coupling is emerging as an alternative strategy. The resurgence of electrochemistry offers an ideal method for electrochemical reductive of cross-coupling electrophiles. Inspired by the mechanism of electrochemical metal hydride, our study proposed that Ni-H electrochemically catalyze the hydroarylation coupling of unactivated alkenes with aryl halides. 1,1-Diarylalkanes can be produced effectively. This method have advantages including mild conditions, excellent regioselectivity, and satisfactory yields.
Project description:A UV-mediated hydrophosphinylation of unactivated alkenes with H-phosphinates and hypophosphorous acid under radical free conditions is presented. The reaction affords selectively a large number of structurally diverse organophosphorous compounds in moderate to good yields under mild reaction conditions in the presence of an organic sensitizer as catalyst irradiated by UV-A LEDs. Furthermore, the high yielding hydrophosphinylation in continuous flow is disclosed.
Project description:Asymmetric alkene hydroamination could be a direct route to valuable chiral amines from abundant feedstocks. However, most asymmetric hydroaminations have limited synthetic value because they require a large excess of alkene, occur with modest enantioselectivity, and proceed with limited tolerance of functional groups. We report an enantioselective, intermolecular hydroamination of unactivated terminal alkenes that occurs with equimolar amounts of alkene and amine, tolerates many functional groups, and occurs in high yield, with high enantioselectivity and turnover numbers. Mechanistic studies revealed factors, including reversibility of the addition, reversible oxidation of the product amine, competing isomerization of the alkene reactant, and unfavorable replacement of sacrificial ligands in standard catalyst precursors by the chiral bisphosphine, that needed to be addressed to achieve enantioselective N-H additions to alkenes.
Project description:Catalytic asymmetric sulfenylation of double bonds has been achieved using a BINAM-based phosphoramide catalyst and an electrophilic sulfur source. Simple alkenes as well as styrenes afforded sulfenylated tetrahydrofurans and tetrahydropyrans by closure with pendant hydroxyl or carboxyl groups. Intermolecular thiofunctionalizations were also achieved with simple alcohols or carboxylic acids as the nucleophiles.
Project description:A mild, versatile, and convenient method for the efficient oxytrifluoromethylation of unactivated alkenes based on a copper-catalyzed oxidative difunctionalization strategy has been developed. This methodology provides access to a variety of classes of synthetically useful CF(3)-containing building blocks from simple starting materials.
Project description:Iminoiodinanes comprise a class of hypervalent iodine reagents that is often encountered in nitrogen-group transfer (NGT) catalysis. In general, transition metal catalysts are required to effect efficient NGT to unactivated olefins because iminoiodinanes are insufficiently electrophilic to engage in direct aziridination chemistry. Here, we demonstrate that 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) activates N-arylsulfonamide-derived iminoiodinanes for the metal-free aziridination of unactivated olefins. 1H NMR and cyclic voltammetry (CV) studies indicate that hydrogen-bonding between HFIP and the iminoiodinane generates an oxidant capable of direct NGT to unactivated olefins. Stereochemical scrambling during aziridination of 1,2-disubstituted olefins is observed and interpreted as evidence that aziridination proceeds via a carbocation intermediate that subsequently cyclizes. These results demonstrate a simple method for activating iminoiodinane reagents, provide analysis of the extent of activation achieved by H-bonding, and indicate the potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis.
Project description:The base-induced reaction of aryl diazonium salts with commercially available CF3SO2Na/CF2HSO2Na allows for the generation of the corresponding diazene radicals along with fluoromethyl radicals. The addition of fluoromethyl radicals to alkenes with subsequent diazene trapping provides the azofluoromethylation products in good to excellent yields. This metal-free method under mild reaction conditions has broad functional group compatibility and is applicable in the late-stage modification of various natural products and bioactive molecules.