Gold(I)-Catalyzed Benzylic C(sp3)−H Functionalizations: Divergent Synthesis of Indole[a]- and [b]-Fused Polycycles**

Phenyl azides substituted by an (alkylphenyl)ethynyl group facilitate benzylic sp³(C−H) functionalization in the presence of a JohnPhosAu catalyst, resulting in indole-fused tetra- and pentacycles via divergent N- or C-cyclization. The chemoselectivity is influenced depending on the counter-anion, the electron density of the α-imino gold(I) carbene, and the alkyl groups stabilizing the benzylic carbocation originating from a 1,5-hydride shift. An isotopic labeling experiment demonstrates the involvement of an indolylgold(I) species resulting from a tautomerization that is much faster than the deauration. The formation of a benzylic sp³(C−H) functionalization leading to an indole-fused seven-membered ring is also demonstrated.     

Synthesis of Highly Substituted Pyridines through Copper-Catalyzed Condensation of Oximes and α,β-Unsaturated Imines

A copper-catalyzed condensation reaction of oxime acetates and α,β-unsaturated ketimines to give pyridine derivatives is reported. The reaction features mild conditions, high functional-group compatibility, and high regioselectivity with respect to unsymmetrical oxime acetates, thus allowing the preparation of a wide range of polysubstituted pyridines, many of which are not readily accessible by conventional condensation methods.     

Copper(I)-Catalyzed Enantioselective Nucleophilic Borylation of Aliphatic Ketones: Synthesis of Enantioenriched Chiral Tertiary α-Hydroxyboronates

A new method was developed for the first catalytic enantioselective borylation of aliphatic ketones. A variety of substrates reacted efficiently with bis(pinacolato)diboron in the presence of a copper(I)/chiral N-heterocyclic carbene complex catalyst to furnish optically active tertiary α-hydroxyboronates with moderate to high enantioselectivities (up to 94 % ee). Notably, the product could be converted into the chiral tertiary alcohol derivative using a stereospecific boron functionalization process. The theoretical study of the mechanism for the enantioselectivity is also described.     

Rhodium(III)-Catalyzed Enantio- and Diastereoselective C−H Cyclopropylation of N-Phenoxylsulfonamides: Combined Experimental and Computational Studies

Cyclopropane rings are a prominent structural motif in biologically active molecules. Enantio- and diastereoselective construction of cyclopropanes through C−H activation of arenes and coupling with readily available cyclopropenes is highly appealing but remains a challenge. A dual directing-group-assisted C−H activation strategy was used to realize mild and redox-neutral Rh^III-catalyzed C−H activation and cyclopropylation of N-phenoxylsulfonamides in a highly enantioselective, diastereoselective, and regioselective fashion with cyclopropenyl secondary alcohols as a cyclopropylating reagent. Synthetic applications are demonstrated to highlight the potential of the developed method. Integrated experimental and computational mechanistic studies revealed that the reaction proceeds via a Rh^V nitrenoid intermediate, and Noyori-type outer sphere concerted proton-hydride transfer from the secondary alcohol to the Rh=N bond produces the observed trans selectivity.     

Gold(I)-Catalyzed and PTSA-Promoted Cycloisomerization of Ynamides to Access Pyrrole Substituted α,β-Unsaturated Ketones**

Substituted pyrroles are prevalent aromatic ring systems encountered in numerous natural products and bioactive molecules. Herein, a novel ynamide scaffold has been designed, synthesized and subsequently applied to an unprecedented gold-catalyzed and para-toluenesulfonic acid (PTSA)-assisted cascade cycloisomerization reaction for the synthesis of β-pyrrole substituted α,β-unsaturated ketones. Notably, the reaction is stereoselective, offering E-isomer as major product with low to moderate yield.     

Rh(I)-Catalyzed Enantioselective Hydrogenation of α-Substituted Ethenylphosphonic Acids

A class of chiral Rh(I) catalysts containing monodentate phosphorous acid diesters tautomerized from the corresponding secondary phosphine oxides was discovered by serendipitous hydrolysis of phosphoramidite ligands. The evolved catalysts demonstrated unprecedented enantioselectivities (98-99% ee) and high catalytic activities (as low as 0.01 mol% catalyst loading) in asymmetric hydrogenations of a wide variety of α-aryl-/alkyl-substituted ethenylphosphonic acids, providing a facile approach to the corresponding enantiopure phosphonic acids with significant biological importance.     

Copper(I)-Catalyzed Click Chemistry-Based Synthesis and Antimicrobial Evaluation of Triazolopyridine–Triazole Congeners

Russian Journal of Organic Chemistry - In an effort to find a new pharmacologically dynamic molecule, we report here the synthesis and in vitro antimicrobial activity of...     

Synthesis of 1,3-dioxo-substituted allenes via copper(I)-catalyzed coupling of α-oxo-alkynes and α-oxo-diazos by controlling the sequence of adding substrates

A novel direct synthesis of 1,3-dioxo-substituted allenes was developed by copper(I)-catalyzed coupling of α-oxo-alkynes and α-oxo-diazos. It was a sequence of adding substrates-controlled method and the desired products were synthesized chemoselectively by adding α-oxo-alkyne terminally.     

Copper (I) Iodide-Catalyzed Solvent-Free Synthesis of α-Aminophosphonates

Abstract

A method for the synthesis of α-aminophosphonates through the three-component coupling reaction of aldehydes, amines, and diisopropyl phosphite using copper (I) iodide salt catalyst is demonstrated, The reaction is highly efficient, economic, and also environment friendly.

[Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Table S1, Figures S1–S9.]

GRAPHICAL ABSTRACT      

Cu(II) Complexes with Optically Active α-Alkylamino Oximes of Caryophyllene Type: Synthesis,Structure, and Properties

Paramagnetic complexes Cu(HL¹)Cl₂ (I), Cu(HL²)Cl₂ · 2H₂O (II), and Cu(HL¹)Br₂ (III) are synthesized by the reaction of copper(II) halides with the optically active -alkylamino oximes HL¹ and HL² of caryophyllene type. Crystal and molecular structures of complex I are determined. The crystals are orthorhombic: a = 9.038(2) Å, b = 11.990(2) Å, c = 11.990(2) Å, V = 2004.8(7) ų, space group P2₁2₁2₁, Z = 4, (calcd) = 1.812 g/cm³, R ₁ = 0.0632. In a mononuclear complex I, the coordination polyhedron of CuCl₂N₂ is a distorted square. The structures of complexes II and III are suggested on the basis of EPR, IR and Raman spectroscopy data.     

Gold(I)-Catalyzed Intramolecular C(sp3)−H Insertion by Decarbenation of Cycloheptatrienes

A novel synthesis of indanes and dihydronaphtalenes based on the intramolecular insertion into C(sp³)−H bonds of gold(I) carbenes generated by retro-Buchner reaction (decarbenation) has been developed. Deuterium-labeling and kinetic isotope effect experiments, DFT calculations, and generation of the proposed carbene intermediate from a well-characterized gold(I) carbenoid support the involvement of a three-center concerted mechanism for the C(sp³)−H functionalization process.     

1,3-Sulfinate Migration Triggered by α-Imino Carbene and Divergent Zwitterion Cyclization: Synthesis of Cyclopropane,Dihydropyrrole, and Azepane Ring Systems

Cyclopropane, dihydropyrrole, and azepane ring systems were synthesized conveniently from sulfinate-tethered triazoles. The divergent synthetic strategy started with the unique 1,3-sulfinate migration of an α-imino carbene. The efficient reaction allowed control of the zwitterion bearing multiple reactive sites depending on the increased stability of the resulting carbocation and anion. The sulfinate was converted to a sulfone after the group migration, and a stable anion bearing two electron-withdrawing groups was thus formed. Catalytic amounts of iodide acted as a switch for the synthesis of cyclopropanes and dihydropyrroles. The reaction merits including readily available substrates, mild reaction conditions, and excellent functional group compatibility qualified this protocol a possible synthetic tool for cyclic compounds, especially for N-heterocycles.     

Asymmetric Synthesis of Chiral 1,3-Disubstituted Allylsilanes via Copper(Ⅰ)-Catalyzed 1,4-Conjugate Silylation of α,β-Unsaturated Sulfones and Subsequent Julia-Kocienski Olefination

Main observation and conclusion A general synthesis of chiral 1,3-disubstituted allylsilanes is established through copper(Ⅰ)-catalyzed asymmetric 1,4-conjugate...     

Enantioselective Synthesis of N−N Biaryl Atropisomers through Iridium(I)-Catalyzed C−H Alkylation with Acrylates

Enantioselective synthesis of N−N biaryl atropisomers is an emerging area but remains underexplored. The development of efficient synthesis of N−N biaryl atropisomers is in great demand. Herein, the construction of N−N biaryl atropisomers through iridium-catalyzed asymmetric C−H alkylation is reported for the first time. In the presence of readily available Ir precursor and Xyl-BINAP, a variety of axially chiral molecules based on indole-pyrrole skeleton were obtained in good yields (up to 98 %) with excellent enantioselectivity (up to 99 % ee). In addition, N−N bispyrrole atropisomers could also be synthesized in excellent yields and enantioselectivity. This method features perfect atom economy, wide substrate scope, and multifunctionalized products allowing diverse transformations.     

Gold(I)-catalyzed cycloisomerization of β-alkynylpropiolactones to substituted α-pyrones

Substituted α-pyrones were straightforwardly synthesized in good to excellent yields by a new gold(I)-catalyzed rearrangement of β-alkynylpropiolactones.     

Rhodium(III)-Catalyzed Asymmetric Access to Spirocycles through C−H Activation and Axial-to-Central Chirality Transfer

Axial-to-central chirality transfer is an important strategy to construct chiral centers, where the axially chiral reagents are mostly limited to atropomerically stable ones. Reported herein is a Rh^III-catalyzed enantioselective spiroannulative synthesis of nitrones. The coupling proceeds via C−H arylation to give an atropomerically metastable biaryl, followed by intramolecular dearomative trapping under oxidative conditions with high degree of chirality transfer.     

Synthesis of Axially Chiral Biaryls through Cobalt(II)-Catalyzed Atroposelective C−H Arylation

Highly efficient synthesis of axially chiral biaryl amines through cobalt-catalyzed atroposelective C−H arylation using easily accessible cobalt(II) salt and salicyloxazoline ligand has been reported. This methodology provides a straightforward and sustainable access to a broad range of enantioenriched biaryl-2-amines in good yields (up to 99 %) with excellent enantioselectivities (up to 99 % ee). The synthetic utility of the unprecedented method is highlighted by its scalability and diverse transformations.     

Escaping from Flatland: Stereoconvergent Synthesis of Three-Dimensional Scaffolds via Ruthenium(II)-Catalyzed Noyori–Ikariya Transfer Hydrogenation

Noyori–Ikariya-type ruthenium(II)-catalysts for asymmetric transfer hydrogenation (ATH) have been known for 25 years and have proved as a well-behaved and user-friendly platform for the synthesis of chiral secondary alcohols. A progress has been made in the past five years in understanding the asymmetric reduction of complex ketones, where up to four stereocenters can be controlled in a single chemical transformation. Intriguing multi-chiral molecular architectures are therefore available in few well understood and robust synthetic steps from commercially available building blocks and possess handles for additional functionalization. The aim of this Review is to showcase the availability of three-dimensional scaffolds and homochiral lead-like compounds via ATH and inspire their direct use in drug discovery endeavors. Basic mechanistic insights are provided to demystify the stereo-chemical outcomes, as well as examples of diastereoselective transformations of enantiopure alcohols to give a feeling of how these rigid non-planar molecules can be further elaborated.     

Multigram Synthesis of α- and γ-((Hetera)cyclo)alkylpyridines through α-Arylation of (Hetero)aliphatic Nitriles

A systematic study on the S_nAr reaction of halogenated fluoropyridines and (hetero)aliphatic nitrile anions as an approach to the synthesis of functionalized pyridines bearing a (cyclo)alkyl or saturated heterocyclic substituent by is described. The scope of the method was demonstrated on a wide range of (hetero)aliphatic nitriles (including three- to six-membered cycloalkane derivatives and N-, O-, S-containing saturated heterocycles) and all isomeric halogenated 2-and 4-fluoropyridines. High chemo- and regioselectivity (i. e., exclusive substitution of the fluorine atom), as well as excellent scalability of the proposed reaction sequence were demonstrated (up to 450 g for the arylation step or up to 77 g of cycloalkylpyridine over two steps in a single run). The utility of the synthesized products was illustrated in the additional functional group transformations resulting in synthetically valuable pyridine-containing building blocks.