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

A Pd(II)/N,N'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available ß-substituted 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.

Annulative Aminosulfonylation of Unactivated Alkenes for Accessing Pyrazolines via Multicomponent SO2 Insertion.

A direct arylsulfonylation of ß,γ-unsaturated hydrazones method, in which sulfonated pyrazolines are accessed by a three-component reaction of ß,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.

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

A catalytic site-selective ring deconstruction of cyclobuteno[a]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.

PhI(OAc)2-mediated aminoacyloxylation of ß,γ-unsaturated hydrazones using Togni reagent II as an acyloxyl precursor.

A metal-free protocol for the direct construction of C(sp2)-N and C-O bonds via a PhI(OAc)2-mediated dehydrogenative aminoacyloxylation of ß,γ-unsaturated hydrazones with Togni reagent II is reported. Initiated by the carboxyl-containing species generated in situ from Togni reagent II, this method offers a new solution for regioselective functionalization at a remote site on ß,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.

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

A palladium-catalyzed asymmetric annulative allylic alkylation reaction of 2-[(1H-indol-2-yl)methyl]malonates with (E)-but-2-ene-1,4-diyl dicarbonates is described, leading to the regio- and enantioselective synthesis of dihydropyrido[1,2-a]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.

Diastereoselective Generation of C2-Azlactonized 2H-Chromenes via Brønsted Acid-Catalyzed Oxo-Cyclization of Propargyl Alcohols.

A new Brønsted acid-catalyzed oxo-cyclization of propargyl alcohols with azlactones to synthesize C2-azlactonized 2H-chromenes has been established that uses 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BiNPO4H) 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 C2-functionalized 2H-chromene scaffold.

Tunable Electrocatalytic Annulations of o-Arylalkynylanilines: Green and Switchable Syntheses of Skeletally Diverse Indoles.

Tunable electrocatalytic annulation reactions of o-arylalkynylanilines have been established, leading to green and divergent syntheses of skeletally diverse indoles by adjusting the electrolytes and the solvents. The presence of ammonium halides as the electrolytes enabled the halogenation of o-arylalkynylanilines to give C3-halogenated indoles whereas naphtho[1',2':4,5]furo[3,2-b]indoles could be obtained by changing the electrolyte from ammonium halides to KI. Interestingly, by combining acetone as the solvent and both NH4I and NH4Cl as the electrolytes, the reaction worked through an intramolecular annulation and [5 + 1] cyclization cascade to form naphtho[1',2':5,6][1,3]oxazino[3,4-a]indoles.

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. This process driven by copper catalyst makes readily available cyclic oxime esters as bifunctional reagents to demonstrate convergent synthesis.

Palladium/N,N'-Disulfonyl Bisimidazoline-Catalyzed Enantioselective Addition of Arylboronic Acids to Cyclic N-Sulfonyl Ketimines.

The combination of Pd(TFA)2 and an N,N'-disulfonyl bisimidazoline ligand shows high catalytic activity and excellent asymmetric induction in the addition of arylboronic acids to cyclic N-sulfonyl ketimines including benzo[d]isothiazole-1,1-dioxides, benzo[e][1,2,3]oxathiazine-2,2-dioxides, and 1,2,5-thiadiazole-1,1-dioxides, by which three types of chiral quaternary carbon-containing sultams with substantial substitution diversity were synthesized with high yields and excellent enantioselectivities (up to >99% ee). The current catalysis demonstrated a remarkable tolerance to oxygen and thus provided an operationally simple approach for constructing enantioenriched cyclic quaternary stereocenters.

Ligand-Free Pd-Catalyzed Synthesis of 3-Allylbenzofurans by Merging Decarboxylative Allylation and Nucleophilic Cyclization.

A new single Pd-catalyzed decarboxylative allylation-nucleophilic cyclization relay is reported by using α-alkynyl arylols and vinylethylene carbonates (or vinyl carbamates), and a wide range of 3-allyl benzofurans with generally good yields were stereoselectively synthesized under mild conditions, among which the complete stereoselectivity of some cases was also observed. Notably, the present catalysts can tolerate air conditions without any ligand, additive, or base, opening new avenues to build up oxa-heterocycle frameworks through catalytic difunctionalization of internal alkynes.

Generation of 1,3-Dimethylene-Substituted Isobenzofurans via Pd(II)-Catalyzed Selective Oxo-cyclization/SO2 Insertion Cascade of ß-Alkynyl Ketones.

A new palladium(II)-catalyzed cyclization-radical addition cascade enables the direct construction of 1,3-dimethylene-substituted isobenzofuran derivatives containing a vinyl aryl sulfone unit in good yields by treating with ß-alkynyl ketones, aryl diazonium salts, and DABCO·(SO2)2. The oxidant-free multicomponent reaction features good substrate scope and functional group tolerance, which proceeds through a sequence of Heck coupling, oxo-cyclization, and SO2 insertion.

Synthesis of Diastereoenriched 1-Indanones via Double-Base Cooperatively Promoted 1,4-Oxo-Migration/Cyclization of ß-Alkynyl Ketones.

A double-base copromoted 1,4-oxo-migration/cyclization cascade of ß-alkynyl ketones was reported, enabling to form a range of functionalized 1-indanones with moderate to good yields and high diastereoselectivity in the presence of t-BuOK as a Brønsted base and N,N'-dimethylethanediamine (DMEDA) as a Lewis base. Some of these 1-indanones were successfully transformed into 2-haloethyl benzoates with one all-carbon quaternary stereocenter by 1,2-dichloroethane (DCE) or 1,2-dibromoethane (DBE) as both a reactant and a reaction media. This method also features high atomic utilization (100%), high diastereoselectivity, and mild reaction conditions.

Completely Stereoselective Synthesis of Sulfonated 1,3-Dihydroisobenzofurans via Radical Multicomponent Reactions.

Two types of new oxidant-free radical multicomponent reactions of ß-alkynyl ketones, aryldiazonium salts, and DABCO·(SO2)2 (DABSO) were established, leading to the tunable generation of two class of sulfonated 1,3-dihydroisobenzofurans with moderate to good yields and complete stereoselectivity under the mild conditions. The radical-induced scission/recombination of the C(sp3)-C(sp3) bond enabled direct 1,8-halosulfonylation of ß-alkynyl ketones, giving 1,3-dimethylene-substituted (1Z,3Z)-1,3-dihydroisobenzofurans with substituent diversity by p-nitrobenzyl bromide (PNBB) or p-nitrobenzyl chloride (PNBC) as the halo source. Fine-tuning substituents to strong electron-withdrawing ones, such as nitro, cyano, and trifluoromethyl, linked to aryldiazonium tetrafluoroborates allowed a different annulation/1,5-azosulfonylation process to access sulfonated (Z)-1,3-dihydroisobenzofurans with one quaternary carbon-amino functionality.

Substrate-Controlled Generation of 3-Sulfonylated 1-Indenones and 3-Arylated ( Z)-Indenes via Cu-Catalyzed Radical Cyclization Cascades of o-Alkynylbenzonitriles.

Substrate-controlled generation of 3-sulfonylated 1-indenones and 3-arylated ( Z)-indenes through radical cyclization cascades of o-alkynylbenzonitriles with sulfonyl hydrazides was established by combining copper(II) with tert-butyl hydroperoxide (TBHP) as a catalytic oxidative system. With the installation of the aryl group (R1) into the alkynyl unit, sulfonyl radicals triggered addition-cyclization cascades to access 3-sulfonylated 1-indenones with good yields by using a Cu/TBHP system, whereas a series of new functionalized 3-arylated ( Z)-indenes were obtained in good yields when o-alkynylbenzonitriles bearing the alkyl group in the alkynyl unit were subjected with arylsulfonyl hydrazides with an electron-rich nature under the above conditions.

Pd(II)-Catalyzed Carbonyl-Directing Activation of Alkenes: Selective Fluorosulfonylation and Aminosulfonylation of 1,7-Enynes.

A new Pd(II)-catalyzed carbonyl-directing activation of alkenes has been established, enabling radical-induced selective fluorosulfonylation and aminosulfonylation of carbonyl-tethered 1,7-enynes with sulfinic acids and N-fluorobenzenesulfonimide (NFSI) under mild and redox neutral conditions to access densely functionalized ( E)-3,4-dihydronaphthalen-1(2 H)-ones with generally good yields and high stereoselectivity. The selectivity of these bifunctionalizations relies on the electronic nature of substituents on both aryl rings of 1,7-enynes.

I2-Mediated Iodobenzannulation of Yne-Allenones toward 1-Naphthols and Their Synthetic Application.

A new I2-mediated iodobenzannulation of yne-allenones has been established, enabling breaking/rearranging of C≡C bonds to selectively access 4-iodonaphthalen-1-ols with generally good yields. The resulting 4-iodonaphthalen-1-ols could serve as a new and reliable coupling reagent, which further reacted with H2O under the oxygen conditions to generate unexpected 1,2-carbonyls with good yields through Pd-catalyzed deiodinated carbonylation, whereas employment of benzene-1,2-diamine as the nucleophile rendered 3-(quinoxalin-2-yl)naphthalen-1-ols through Pd-catalyzed [4 + 2] heterocyclization. On the basis of the controlled experiments, the mechanism for forming 1,2-carbonyls was proposed, including an oxidative addition, 1,3-palladium migration, reductive elimination, and oxidative dehydrogenation sequence.

Atom-economic synthesis of cyclobuta[a]naphthalen-4-ols via a base-promoted [2 + 2] cycloaddition/1,6-nucleophilic addition cascade.

A first atom-economic [2 + 2] cycloaddition/1,6-conjugate addition cascade of yne-allenones with C-nucleophiles including 1,3-dicarbonyls and α,α-dicyanoolefins under base-promoted conditions has been established, enabling the direct construction of C(sp3)-C(sp3) bonds to generate cyclobuta[a]naphthalen-1-ols with generally good yields. These resulting products have a cyclobutene unit that contains both an aryl and alkyl group.

Silver/Scandium-Cocatalyzed Bicyclization of ß-Alkynyl Ketones Leading to Benzo[c]xanthenes and Naphtho[1,2-b]benzofurans.

The combination of AgTFA and Sc(OTf)3 enables the bimetallic synergistic catalysis of ß-alkynyl ketones and para-quinone methides (p-QMs), allowing direct synthesis of 17 examples of benzo[c]xanthenes with generally good yields through a benzannulation/1,6-addition/cyclization sequence. Exchanging p-QMs for quinone imine ketal resulted in 10 examples of tetracyclic naphtho[1,2-b]benzofurans via a similar benzannulation/1,4-addition/cyclization cascade. During these reaction processes, AgTFA and Sc(OTf)3 could be perfectly compatible, together with the realization of C(sp3)-H functionalization adjacent to carbonyl group on the ß-alkynyl ketone unit.

Synthesis of Diastereoenriched Oxazolo[5,4-b]indoles via Catalyst-Free Multicomponent Bicyclizations.

A new and highly eco-friendly approach to diverse and functionalized oxazolo[5,4-b]indoles with good yield and high diastereoselectivity (up to >99:1) has been disclosed from simple and readily available arylglyoxals with cyclic enaminones and amino acids. These microwave-assisted transformations in environmentally compatible ethanol resulted in continuous multiple bond-forming events including C-C, C-N, and C-O bonds, enabling catalyst-free multicomponent bicyclizations to rapidly build up functional N,O-heterocycles.

Radical Deaminative ipso-Cyclization of 4-Methoxyanilines with 1,7-Enynes for Accessing Spirocyclohexadienone-Containing Cyclopenta[c]quinolin-4-ones.

A new C-center radical-triggered bicyclization cascade of N-tethered 1,7-enynes for forming 28 examples of biologically interesting spirocyclohexadienone-containing cyclopenta[c]quinolin-4-ones with two all-carbon quaternary stereocenters has been established under mild conditions. The in situ generated diazonium salts from 4-methoxyanilines and t-BuONO are served as 4-methoxyphenyl precursors without additional oxidant, enabling 6-exo-dig cyclization/5-exo-trig ipso-cyclization to construct three new C-C bonds through metal-free dearomatization. The reaction also features broad substrate scope, annulation efficiency, and high functional group tolerance.