Sulfoxides are classical functional groups for directing the stoichiometric metalation and functionalization of C−H bonds. In recent times, sulfoxides have been given a new lease on life owing to the ...development of modern synthetic methods that have arisen because of their unique reactivity. They have recently been used in catalytic C−H activation proceeding via coordination of an internal sulfoxide to a metal or through the action of an external sulfoxide ligand. Furthermore, sulfoxides are able to capture nucleophiles and electrophiles to give sulfonium salts, which subsequently enable the formation of C−C bonds at the expense of C−H bonds. This Review summarizes a renaissance period in the application of sulfoxides arising from their versatility in directing C−H functionalization.
Classical sulfoxide directing groups have been given a new lease on life because of their unique ability to direct a variety of C−H couplings to form important C−C bonds. Sulfoxide direction operates through internal coordination to a metal (directing groups), through external coordination (ligands), or via sulfoxide capture of nucleophilic or electrophilic coupling partners (sulfonium‐directed).
A transition metal‐free one‐pot stereoselective approach to substituted (E,Z)‐1,3‐dienes was developed by using an interrupted Pummerer reaction/ligand‐coupling strategy. Readily available ...benzothiophene S‐oxides, which can be conveniently prepared by oxidation of the parent benzothiophenes, undergo Pummerer coupling with styrenes. Reaction of the resultant sulfonium salts with alkyllithium/magnesium reagents generates underexploited hypervalent sulfurane intermediates that undergo selective ligand coupling, resulting in dismantling of the benzothiophene motif and the formation of decorated (E,Z)‐1,3‐dienes.
Double couple, no trouble: A transition‐metal‐free stereoselective one pot synthesis of (E,Z)‐1,3‐dienes proceeds through an interrupted Pummerer reaction/ligand‐coupling sequence. Readily accessible yet underexplored benzothiophene S‐oxides couple with styrene partners, and the addition of an organometallic reagent triggers controlled dismantling of the benzothiophene scaffold by selective ligand coupling in rarely exploited sulfurane intermediates.
A highly enantio‐ and diastereoselective copper‐catalyzed three‐component coupling affords the first general synthesis of homoallylic amines bearing adjacent stereocenters from achiral starting ...materials. The method utilizes a commercially available NHC ligand and copper source, operates at ambient temperature, couples readily available simple imines, allenes, and diboranes, and yields high‐value homoallylic amines that exhibit versatile amino, alkenyl, and boryl units.
A copper‐catalyzed three‐component coupling affords homoallylic amines with adjacent stereocenters from achiral starting materials with high enantio‐ and diastereoselectivity. The method utilizes a commercially available NHC ligand and copper source, operates at ambient temperature, couples simple imines, allenes, and diboranes, and yields valuable homoallylic amines with versatile amino, alkenyl, and boryl units.
A dual vicinal functionalisation cascade involving the union of heterocycles and allyl sulfoxides is described. In particular, the approach provides efficient one-step access to biologically relevant ...and synthetically important C3 thio, C2 carbo substituted indoles. The reaction operates under mild, metal free conditions and without directing groups,
an interrupted Pummerer coupling of activated allyl sulfoxides, generating allyl heteroaryl sulfonium salts that are predisposed to a charge accelerated 3,3-sigmatropic rearrangement.
Copper catalyzed multi‐functionalization of unsaturated carbon‐carbon bonds is a powerful tool for the generation of complex molecules. We report a regiodivergent process that allows a switch between ...1,4‐borocupration and 4,1‐borocupration of 1,3‐dienes upon a simple change in ligand. The subsequently generated allyl coppers are trapped in an electrophilic cyanation to selectively generate densely functionalized and synthetically versatile 1,2‐ or 4,3‐borocyanation products.
A powerful tool for the generation of complex molecules is the copper catalyzed multi‐functionalization of unsaturated carbon‐carbon bonds. A regiodivergent process that allows a switch between 1,4‐ and 4,1‐borocupration of 1,3‐dienes upon a simple change in ligand is described.
We report a transition-metal-free synthesis of benzofurans from benzothiophenes and phenols that exploits the unique reactivity of sulfoxides. Through a sequence involving an interrupted Pummerer ...reaction and 3,3 sigmatropic rearrangement, phenols can be combined with readily accessible yet synthetically unexplored benzothiophene S-oxides to provide C3-arylated benzofuran products. The products from this approach can undergo subsequent functionalization to gain access to a range of important benzofuran derivatives.
The direct functionalisation of allenes under copper catalysis enables efficient access to enantioenriched, densely functionalised molecules. In this review we explore the breadth and depth of a ...versatile reaction manifold, which involves the element-cupration of allenes to generate allyl copper intermediates that are subsequently coupled with diverse arrays of electrophiles.
We explore the breadth of the copper catalysed functionalisation of allenes, which enables efficient access to enantioenriched, densely functionalised molecules.
The manipulation of amino C-H bonds has garnered significant interest from the synthetic community due to its inherently high atom, step and redox economy. This Tutorial Review summarises the ability ...of boranes to mediate hydride abstraction from α-amino and γ-amino conjugated C-H bonds. Borane-mediated hydride abstraction results in the generation of reactive iminium hydridoborate salts that participate in a variety of stoichiometric and catalytic processes. The reactions that have utilised this unusual reactivity include those that manipulate amino scaffolds (including dehydrogenation, racemisation, isomerisation, α- and β-functionalisation, and C-N bond cleavage) and those that use amine-based reagents (transfer hydrogenation, and alkylation).
Borane mediated hydride abstraction of amines efficiently generates useful iminium salts. This review explores this fascinating reactivity and discusses how the iminium intermediates are utilised in a variety of stoichiometric and catalytic processes.
A benzothiophene S‐oxide catalyst, generated in situ by sulfur oxidation with H2O2, mediates the oxidative coupling of 2‐naphthols. Key to the catalytic process is the capture and inversion of ...reactivity of a 2‐naphthol partner, using an interrupted Pummerer reaction of an unusual benzothiophene S‐oxide, followed by subsequent coupling with a second partner. The new catalytic manifold has been showcased in the synthesis of the bioactive natural products, (±)‐nigerone and (±)‐isonigerone. Although Pummerer reactions are used widely, their application in catalysis is rare, and our approach represents a new catalytic manifold for metal‐free C−C bond formation.
Metal‐free coupling: A benzothiophene S‐oxide catalyst, generated in situ using H2O2, mediates the oxidative coupling of 2‐naphthols. Key to the catalytic process is the capture and inversion of reactivity of one partner, using an interrupted Pummerer reaction, followed by coupling with a second partner. The new catalytic manifold has been showcased in the synthesis of bioactive natural products.
Metal-free C-H thioarylation of arenes and heteroarenes using methyl sulfoxides constitutes a general protocol for the synthesis of high value diaryl sulfides. The coupling of arenes and heteroarenes ...with in situ activated sulfoxides is regioselective, uses readily available starting materials, is operationally simple, and tolerates a wide range of functional groups.
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