Gold Self-Relay Catalysis Enabling Regioselective Bicyclization toward [5]Azahelicenes.

A gold self-relay catalysis driving a double annulation cascade starting from soft electron-biased 1,2-di(-aminoaryl)alkynes and aldehydes is reported, enabling regioselective access to produce a series of [5]azahelicenes depending on the substitution pattern in generally good yields under mild conditions. This protocol exploits and unifies the π- and σ-Lewis acid capability of gold catalysts, featuring high molecular convergence, broad substrate flexibility, and good functional group compatibility and regioselectivity.

Construction of central and axial chirality Pd(II)/Bim-catalyzed asymmetric dearomative Michael reaction of polycyclic tropones.

A highly enantioselective Pd/Bim-catalyzed dearomative Michael reaction applying polycyclic tropones as non-benzenoid aromatic Michael acceptors and arylboronic acids as aryl pronucleophiles has been developed. The bridged biaryls bearing central and axial chirality, including pentacyclic cyclohepta[]indoles and 6,7-dihydrodibenzo[,][7]annulen-5-ones, are generally generated in good to high yields and excellent enantioselectivities and can be readily transformed into useful derivatives.

Pd(II)/,'-Disulfonyl Bisimidazoline-Catalyzed Enantioselective Synthesis of Cyclic Quaternary Centers and Mechanistic Investigations.

A Pd(II)/,'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available βsubstituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.

Photocatalytic Bicyclization of Indole-Tethered 1,6-Enynes for Diastereoselective Synthesis of Pyrrolo[3,2,1-]carbazoles.

A visible-light-driven photocatalytic protocol is established for the diastereoselective synthesis of pyrrolo[3,2,1-]carbazoles via a radical-triggered multicomponent bicyclization reaction starting from readily available indole-tethered 1,6-enynes and α-benzyl-α-bromomalonates under mild conditions. This photocatalytic approach exhibits a wide substrate compatibility and excellent tolerability toward various functional groups and boasts the benefit of efficient ring formation and chemical bond creation.

Olefin skeletal rearrangement enabling access to multiarylated -sulfonyl amidines.

A base-promoted olefin skeletal rearrangement strategy from -quinone methides (-QMs) and -fluoroarenesulfonamides is reported, enabling direct nitrogen insertion of olefins to produce a series of multiarylated ()--sulfonyl amidines with complete stereoselectivity and generally good yields. Using -QMs without -hydroxy substituents gave triarylated -sulfonyl amidines, whereas tetraarylated ,'-disulfonyl amidines were synthesized with the existence of -hydroxy groups.

Copper(II)/DBU Relay Catalyzed Annulation of α-Carbonyl-γ-alkynyl Sulfoxonium Ylides for Accessing -Sulfonamido 2-Isoindoles.

A copper(II)/DBU relay catalyzed annulation of α-carbonyl-γ-alkynyl sulfoxonium ylides as a new class of sulfoxonium ylide reagents with sulfonyl hydrazides is reported, enabling intramolecular oxygen migration to produce a series of -sulfonamido 2-isoindoles with good yields. The present annulation proceeded readily by combining the Cu(II)-catalyzed 6- oxo-cyclization with the DBU-catalyzed isochromene skeletal rearrangement, resulting in the formation of multiple new chemical bonds.

PhI(OAc)-mediated aminoacyloxylation of β,γ-unsaturated hydrazones using Togni reagent II as an acyloxyl precursor.

A metal-free protocol for the direct construction of C(sp)-N and C-O bonds a PhI(OAc)-mediated dehydrogenative aminoacyloxylation of β,γ-unsaturated hydrazones with Togni reagent II is reported. Initiated by the carboxyl-containing species generated from Togni reagent II, this method offers a new solution for regioselective functionalization at a remote site on β,γ-unsaturated hydrazones, thus providing a straightforward method for the synthesis of acyloxyl-substituted pyridazines. This reaction features a broad substrate scope and mild conditions.

Pd-Catalyzed Asymmetric Annulative Dearomatization of Phenols for Regio- and Enantioselective Synthesis of Spirocyclohexadienones.

A palladium-catalyzed asymmetric annulative dearomatization of phenols with butene dicarbonate is reported, enabling twofold decarboxylative allylation to regioselectively produce a range of spirocyclohexadienones with 29-95% yields and 74-99% ee. A catalytic dearomative formal [4 + 2] cyclization of 1,1'-biphenyl-2,4'-diols delivered spiro[chromane-4,1'-cyclohexane]-2',5'-dien-4'-ones with high enantioselectivity, whereas enantioenriched spiro[cyclohexane-1,4'-quinoline]-2,5-dien-4-ones were generated starting from 2'-amino-[1,1'-biphenyl]-4-ols as 1,4-dinucleophiles.

Annulative Aminosulfonylation of Unactivated Alkenes for Accessing Pyrazolines via Multicomponent SO Insertion.

A direct arylsulfonylation of β,γ-unsaturated hydrazones method, in which sulfonated pyrazolines are accessed by a three-component reaction of β,γ-unsaturated hydrazones, DABSO, and aryldiazonium tetrafluoroborates, has been developed without external oxidants or catalysts. This transformation is triggered by the formation of arylsulfonyl radicals in situ from the reaction of aryldiazonium tetrafluoroborates and DABSO, and is enabled by controllable generation of C center radical, in which DABSO was utilized as the sulfone source and an oxidant in this radical-mediated cascaded reaction. A wide range of substrates can be applied in this process to afford pyrazolines in good yield, and it is amenable for gram-scale synthesis.

Azofuran activation for annulative rearrangement enabled by gold(I)/Brønsted acid relay catalysis.

A novel gold(I)/Brønsted acid relay catalysis enabling azofuran activation to induce annulative rearrangement from 3-yne-1,2-diols and aryldiazonium tetrafluoroborates is reported, producing a series of furan-2-yl-substituted pyrrol-2-ones bearing a quaternary carbon center with good yields. Exchanging aryldiazonium tetrafluoroborate for azofuran led to skeletally identical but substituent-diverse furan-2-yl-containing pyrrol-2-ones with good yields, supporting the key azofuran activation and annulative rearrangement by gold/Brønsted acid relay catalysis.

Gold self-relay catalysis enabling annulative oxygenation of propargylic alcohols with O-nucleophiles.

A new gold(I) self-relay catalysis reaction enabling the annulative oxygenation of propargylic alcohols with various O-nucleophiles, such as carboxylic acids, alcohols and TBHP, is reported, producing a series of functionalized benzofurans in moderate to good yields under mild conditions. This protocol benefits from the π- and σ-Lewis acid capability of gold complexes, demonstrating high molecular convergence, broad substrate flexibility, high functional group compatibility and mild conditions.

Lewis Acid-Catalyzed Remote Site-Selective Ring Deconstruction of Cyclobuteno[]naphthalene-4-ones to Access Unsymmetric 1,1-Diarylated Olefins.

A catalytic site-selective ring deconstruction of cyclobuteno[]naphthalene-4-ones with alcohols is reported, enabling the direct production of a wide range of unsymmetric 1,1-diarylated olefins with good yields and complete regioselectivity. The late-stage application of these resulting terminal olefins demonstrates great possibilities to apply this strategy to complex molecules. The protocol features good functional group compatibility, broad substrate scope, and controllable site selectivity.

Azoarene activation for Schmidt-type reaction and mechanistic insights.

The Schmidt rearrangement, a reaction that enables C-C or C-H σ bond cleavage and nitrogen insertion across an aldehyde or ketone substrate, is one of the most important and widely used synthetic tools for the installation of amides and nitriles. However, such a reaction frequently requires volatile, potentially explosive, and highly toxic azide reagents as the nitrogen donor, thus limiting its application to some extent. Here, we show a Schmidt-type reaction where aryldiazonium salts act as the nitrogen precursor and in-situ-generated cyclopenta-1,4-dien-1-yl acetates serve as pronucleophiles from gold-catalyzed Nazarov cyclization of 1,3-enyne acetates.

Regio- and Enantioselective Synthesis of Dihydropyrido[1,2-]indoles via Catalytic Asymmetric Annulative Allylic Alkylation.

A palladium-catalyzed asymmetric annulative allylic alkylation reaction of 2-[(1-indol-2-yl)methyl]malonates with ()-but-2-ene-1,4-diyl dicarbonates is described, leading to the regio- and enantioselective synthesis of dihydropyrido[1,2-]indoles with a chiral cyclic allyl stereocenter adjacent to the ring-junction nitrogen atom in moderate to good yields. The salient features of this protocol include mild conditions, a broad substrate scope, and good compatibility with substituents as well as high regio- and stereoselectivities, providing a catalytic asymmetric entry for fabricating chiral pyridoindole scaffolds.

Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation. Immune dysfunction is an essential mechanism in the pathogenesis of RA and directly linked to synovial inflammation and cartilage/bone destruction. Intermediate conductance Ca-activated K channel (KCa3.

Electrochemical selective annulative amino-ketalization and amino-oxygenation of 1,6-enynes.

A new electrochemical selective annulative amino-ketalization and amino-oxygenation of 1,6-enynes with disulfonimides and alcohols is reported, producing a series of functionalized benzofurans under catalyst- and oxidant-free conditions. The annulative aminoketalization proceeds with simple short-chain alcohols such as methanol, ethanol and -propanol as -nucleophilic reagents, while the reaction occurs in the annulative aminooxygenation direction in the presence of water and large steric -butyl alcohol (SBA).

Nitrative bicyclization of 1,7-diynes for accessing skeletally diverse tricyclic pyrroles.

A novel metal-free nitrative bicyclization of 1,7-diynes with BuONO in the presence of HO is reported, producing three types of skeletally diverse tricyclic pyrroles, namely pyrrolo[3,4-]quinolines, chromeno[3,4-]pyrroles and benzo[]isoindoles, with moderate to good yields by simply tuning the linkers of the 1,7-diynes. This domino protocol demonstrates remarkable compatibility regarding 1,7-diynes with different linkers, such as nitrogen and oxygen atoms and a hydroxymethyl group, and BuONO plays dual roles as a nitro precursor as well as a nitrogen atom source.

Diastereoselective Generation of C-Azlactonized 2-Chromenes via Brønsted Acid-Catalyzed Oxo-Cyclization of Propargyl Alcohols.

A new Brønsted acid-catalyzed oxo-cyclization of propargyl alcohols with azlactones to synthesize C-azlactonized 2-chromenes has been established that uses 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BiNPOH) as the catalyst and gives excellent diastereoselectivities (≥19:1 dr) in most cases. This protocol has a high compatibility with various substituents of substrates, offering a catalytic and useful entry to the fabrication of the synthetically important C-functionalized 2-chromene scaffold.

Cyclic Oxime Esters as Deconstructive Bifunctional Reagents for Cyanoalkyl Esterification of 1,6-Enynes.

A concise copper catalysis strategy for the addition-cyclization of cyclic oxime esters across 1,6-enynes with high stereoselectivity to generate 1-indanones bearing an all-carbon quaternary center is reported. In this process, single-electron reduction of cyclic oxime esters enables deconstructive carbon-carbon cleavage to provide a key cyanopropyl radical poised for the addition-cyclization. This reaction is redox-neutral, exhibits good functional group compatibility, and features 100% atomic utilization.

Copper/silver -mediated three-component bicyclization for accessing indeno[1,2-]azepine-3,6-diones.

A new copper/silver-co-mediated three-component bicyclization of benzene-linked 1,6-enynes with ICF2CO2Et with TMSN3 was reported, and used to produce a wide range of hitherto unreported difluorinated tetrahydroindeno[1,2-c]azepine-3,6-diones with moderate to good yields. The mechanistic pathway consists of radical-induced 1,6-addition-cyclization, oxidative addition, reductive elimination, nitrene insertion and N-O cleavage, resulting in continuous multiple bond-forming events including C-C and C-N bonds to build up a 6/5/7 tricyclic framework.

Enantio- and Regioselective CuH-Catalyzed Conjugate Reduction of Yne-Allenones.

A new asymmetric catalytic conjugate reduction of yne-allenones to synthesize enantioenriched cyclobuta[]naphthalen-4(2)-ones has been established that uses copper-bisphosphine complexes as catalysts and gives excellent regio- and enantioselectivities (≥99% ee) in most cases. This protocol tolerates a broad scope of substrates, exhibits high compatibility with various substituents, and gives excellent stereoselectivity, providing a catalytic and efficient entry to fabrication of synthetically important chiral 6-6-4 tricarbocyclic scaffolds.

Engaging yne-allenones in tunable catalytic silane-mediated conjugate transfer reductions.

New tunable catalytic [2+2] cycloaddition/silane-mediated conjugate transfer reductions of yne-allenones have been developed, by which substituent-diverse cyclobutarenes with generally good yields were selectively synthesized by adjusting Fe-H and Cu-H catalytic systems. Use of the Fe-H system triggers 1,6-conjugate reduction to dihydrocyclobuta[a]naphthalen-4-ols whereas the Cu-H complex enables 1,4-conjugate reduction to cyclobuta[a]naphthalen-4(2H)-ones.

Diastereoselective Synthesis of 1,2-Dihydrobenzofuro[3,2-]pyridines via a Carbon-Carbon Double-Bond Cleavage/Rearrangement Cascade.

A new Lewis acid-catalyzed [2 + 2] cycloaddition/retroelectrocyclization (CA-RE)/1,6-addition relay of aurone-derived 1-azadienes and 1-alkynylnaphthalen-2-ols has been reported, leading to the regio- and diastereoselective synthesis of 1,2-dihydrobenzofuro[3,2-]pyridine with a chiral carbon center and an axial chirality in good yields. This protocol enables the C-C double-bond scission/recombination to rapidly construct aza-heterocyclic architectures and features 100% atom utilization, a wide substrate scope, good compatibility with substituents, and excellent diastereoselectivity.