A method for the regiodivergent and stereoselective hydrosilylation of the basic industrial feedstock isoprene with unactivated silanes has been developed using earth‐abundant iron catalysts. The ...manipulation of regioselectivity relies on fine modification of the coordination geometry of the iron center. While a bidentate pyridine imine ligand promoted the formation of allylic silanes through 4,1‐addition, selectivity for the 3,4‐adduct homoallylic silanes was observed with a tridentate nitrogen ligand. Experimental studies and analysis were carried out to elucidate the reaction mechanism and the factors enabling manipulation of the regioselectivity. This study contributes to the art of regioselectivity control in alkene hydrofunctionalization.
A ligand‐regulated regiodivergent and stereoselective hydrosilylation of terpenes has been developed using earth‐abundant iron catalysts. Various silanes and terpenes were transformed with excellent selectivity into the corresponding allylic silanes and homoallylic silanes through 4,1‐ and 3,4‐addition, respectively.
Skeletal reorganization reactions have emerged as an intriguing tool for converting readily available compounds into complicated molecules inaccessible by traditional methods. Herein, we report a ...unique skeleton‐reorganizing coupling reaction of cycloheptatriene and cycloalkenones with amines. In the presence of Rh/acid catalysis, cycloheptatriene can selectively couple with anilines to deliver fused 1,2‐dihydroquinoline products. Mechanistic studies indicate that the retro‐Mannich type ring‐opening and subsequent intramolecular Povarov reaction account for the ring reorganization. Our mechanistic studies also revealed that skeleton‐reorganizing amination between anilines and cycloalkenones can be achieved with acid. The synthetic utilization of this skeleton‐reorganizing coupling reaction was showcased with a gram‐scale reaction, synthetic derivatizations, and the late‐stage modification of commercial drugs.
An unusual catalytic coupling reaction of cycloheptatriene and cycloalkenones with amines proceeds through a skeleton‐reorganization process for the selective synthesis of fused 1,2‐dihydroquinolines. Mechanistic studies indicate that the reactions proceed through a retro‐Mannich‐type ring‐opening and a subsequent intramolecular Povarov process.
The basic industrial feedstock isoprene was employed as a building block to install prenyl and reverse‐prenyl groups onto indoles. The regioselectivity can be manipulated by the choice of metal ...hydride. Reverse‐prenylated indoles were attained with high selectivity when using Rh−H. By switching to a Pd−H catalyst, selectivity toward prenylated indoles was achieved. This regiodivergent method also features high atom economy without stoichiometric byproduct formation.
Backwards and forwards: A metal hydride mediated regiodivergent coupling of indoles with the industrial feedstock isoprene was developed for which the regioselectivity for prenylation versus reverse prenylation is determined by the choice of metal hydride. This method enables the installation of prenyl and reverse‐prenyl motifs onto indoles with high atom economy.
Depending on the reactant property and reaction mechanism, one major regioisomer can be favored in a reaction that involves multiple active sites. Herein, an orthogonal regulation of nucleophilic and ...electrophilic sites in the regiodivergent hydroamination of isoprene with indazoles is demonstrated. Under Pd‐hydride catalysis, the 1,2‐ or 4,3‐insertion pathway with respect to the electrophilic sites on isoprene could be controlled by the choice of ligands. In terms of the nucleophilic sites on indazoles, the reaction occurs at either the N1‐ or N2‐position of indazoles is governed by the acid co‐catalysts. Preliminary experimental studies have been performed to rationalize the mechanism and regioselectivity. This study not only contributes a practical tool for selective functionalization of isoprene, but also provides a guide to manipulate the regioselectivity for the N‐functionalization of indazoles.
The Pd‐catalyzed regiodivergent coupling reactions between indazoles and isoprene have been developed through the orthogonal regulation of nucleophilic and electrophilic sites.
In nature, prenylation and geranylation are two important metabolic processes for the creation of hemiterpenoids and monoterpenoids under enzyme catalysis. Herein, we have demonstrated bioinspired ...unnatural prenylation and geranylation of oxindoles using the basic industrial feedstock isoprene through ligand regulation under Pd catalysis. Pentenylated oxindoles (with C5 added) were attained with high selectivity when using a bisphosphine ligand, whereas upon switching to a monophosphine ligand, selectivity toward geranylated oxindoles (with C10 added) was achieved. Moreover, the head‐to‐head product could be further isomerized to an internal skipped diene under Pd−H catalysis. No stoichiometric by‐product was formed in the process.
A practical strategy has been developed for the bioinspired and ligand‐regulated chemoselective unnatural prenylation and geranylation of oxindoles with isoprene under Pd catalysis. The selectivity was governed by modulating the coordination geometry of the Pd catalyst.
By exploiting the reactivity of a vinyl-Pd species, we control the regioselectivity in hydroallylation of alkynes under Pd-hydride catalysis. A monophosphine ligand and carboxylic acid combination ...promotes 1,5-dienes through a pathway involving isomerization of alkynes to allenes. In contrast, a bisphosphine ligand and copper cocatalyst favor 1,4-dienes
via
a mechanism that involves transmetalation. Our study highlights how to access different isomers by diverting a common organometallic intermediate.
Through rational evaluation of ligands and promoters, the reactivity of a key Pd(
ii
) species towards transmetalation or β-H elimination is manipulated.
Thiophene‐based rings are one of the most widely used building blocks for the synthesis of sulfur‐containing molecules. Inspired by the redox diversity of these features in nature, we demonstrate ...herein a redox‐divergent construction of dihydrothiophenes, thiophenes, and bromothiophenes from the respective readily available allylic alcohols, dimethyl sulfoxide (DMSO), and HBr. The redox‐divergent selectivity could be manipulated mainly by controlling the dosage of DMSO and HBr. Mechanistic studies suggest that DMSO simultaneously acts as an oxidant and a sulfur donor. The synthetic potentials of the products as platform molecules were also demonstrated by various derivatizations, including the preparation of bioactive and functional molecules.
We report herein a redox‐divergent construction of dihydrothiophenes, thiophenes, and bromothiophenes from readily available allylic alcohols, dimethyl sulfoxide (DMSO), and HBr, respectively. This strategy can serve for the programmable and concise synthesis of bioactive and functional molecules.
Terpenes, consisting of isoprene monomer units, represent a family of naturally abundant compounds. The difunctionalization of terpenes is highly appealing yet remains challenging, since the multiple ...unbiased C&z.dbd;C bonds of terpenes lead to difficulty in controlling the regioselectivity. Herein, a cobalt(
iii
)-catalyzed C-H activation strategy has been developed to facilitate hydroxymethylarylation of terpenes with formaldehyde and arenes with high chemo- and regio-selectivities. These (chemo- and regio-) selectivities are governed by the coordination abilities of isoprene, directing groups and the steric effect. This terpene difunctionalization also features high atom and step economy through a C-H addition pathway.
A cobalt(
iii
)-catalyzed C-H activation strategy has been developed to facilitate hydroxymethylarylation of terpenes with formaldehyde and arenes with high chemo- and regio-selectivities.
The Mizoroki-Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Here we report an ...atom-economical cross-coupling of halopyridines and unactivated alkenes under photoredox catalysis to afford a series of alkene halopyridylation products. This protocol with mild and redox neutral conditions contributes broad substrate scope. As a complement to conventional Heck-type reaction, this radical process avoids the involvement of β-H elimination and thus useful pyridyl and halide groups could be simultaneously and regioselectively incorporated onto alkenes. The success depends on TFA-promoted domino photocatalytic oxidative quenching activation and radical-polar crossover pathway. Plausible mechanism is proposed based on mechanistic investigations. Moreover, the reserved C - X bonds of these products are beneficial for performing further synthetic elaborations.
An acid‐catalyzed regiodivergent formal 3+3 annulation of 4‐hydroxycoumarins with isoprene is developed. A variety of pyranocoumarins were obtained exclusively in the presence of strong Brønsted ...acid, while varying to Lewis acid delivered pyranochromones as main products. The protocol also features high atom‐economy, wide substrate scope, easy scale‐up, and good applications in natural product synthesis.
An acid‐catalyzed regiodivergent annulation of biomass‐derived 4‐hydroxycoumarins with isoprene is developed, providing a facile access to pyranocoumarins and pyranochromones.
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