A Palladium Complex as an Asymmetric π-Lewis Base Catalyst for Activating 1,3-Dienes.

Here we report that palladium(0) complexes can coordinate in a η2 fashion to 1,3-dienes and significantly raise the energy of their highest occupied molecular orbital (HOMO) by donating the electrons from the d-orbitals to the empty antibonding molecular orbitals of double bonds (π*) via back-bonding. Thus, the uncoordinated double bond, as a more reactive partner on the basis of the principle of vinylogy, can directly attack imines, furnishing a formal hydrodienylation reaction enantioselectively. A chemoselective cascade vinylogous addition/allylic alkylation difunctionalization process between 1,3-dienes and imines with a nucleophilic group is also compatible, by trapping in situ formed π-allylpalladium species after initial ene addition. This π-Lewis base catalytic mode, featuring simple η2coordination, vinylogous activation, and compatibility with both conjugated neutral polyenes and electron-deficient polyenes, is elucidated by control experiments and density functional theory (DFT) calculations.

Asymmetric (4 + 3) and (4 + 1) Annulations of Isatin-derived Morita-Baylis-Hillman Carbonates to Construct Diverse Chiral Heterocyclic Frameworks.

A chiral tertiary amine-catalyzed asymmetric γ-regioselective (4 + 3) annulation reaction of isatin-derived Morita-Baylis-Hillman carbonates and 1-azadienes was developed, delivering chiral azepane spirooxindoles with excellent stereoselectivity. In addition, by tuning the substituents of Morita-Baylis-Hillman carbonates, the switchable γ-(4 + 3) or α-(4 + 1) annulation reaction with o-quinone methides was observed to furnish benzo[b]oxepines or 2,3-dihydrobenzofurans, respectively, under similar catalytic conditions.

Asymmetric Formal Vinylogous Iminium Ion Activation for Vinyl-Substituted Heteroaryl and Aryl Aldehydes.

The vinyl group tethered to furfurals could be LUMO-lowered by forming formal vinylogous iminium ion intermediates catalyzed by a chiral secondary amine and underwent asymmetric [3 + 2] cycloaddition reactions with N-trifluoroethyl-substituted isatin imines, furnishing a variety of spirooxindoles incorporating a 3,2'-pyrrolidine motif with excellent stereoselectivity. In addition, this strategy has been successfully expanded to a number of vinyl-substituted electron-rich heteroaryl aldehydes and even some specific aryl aldehydes.

Remote Friedel-Crafts Reaction with α-Heteroaryl-Substituted Cyclic Ketones via HOMO Activation of Lewis Bases.

Under the catalysis of Lewis bases, cyclic enones bearing an α-(2-furyl) motif can undergo remote Friedel-Crafts reaction with electrophilic reagents via a HOMO-activation strategy, proceeding in a formal vinylogous Rauhut-Currier or Morita-Baylis-Hillman-type reaction pattern. Moreover, even less reactive α-(2-benzofuranyl)-substituted cyclopeten-2-ones can be similarly HOMO-raised and furnish [4 + 2] products with alkylidenemalononitriles in a cascade Friedel-Crafts/Michael addition process.

Quaternary Phosphonium Salts as Active Brønsted Acid Catalysts for Friedel-Crafts Reactions.

A readily available quaternary phosphonium salt containing a trifluoroacetonyl group and a tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF4-) counterion was demonstrated to be a highly active Brønsted acid catalyst for Friedel-Crafts-type reactions of an array of electron-rich heteroarenes and aniline derivatives with isatin-derived ketimines, even at 0.1 mol % catalyst loadings.

Sequential Assembly of Morita-Baylis-Hillman Carbonates and Activated ortho-Vinylbenzaldehydes To Construct Chiral Methanobenzo[7]annulenone Frameworks.

The α-regioselective asymmetric [3 + 2] annulation reaction of Morita-Baylis-Hillman carbonates from isatins and activated ortho-vinylbenzaldehyses was developed by the catalysis of a chiral tertiary amine. The sequential N-heterocyclic carbene-mediated intramolecular Stetter reaction was conducted to finally furnish the bridged 5,8-methanobenzo[7]annulen-9-one architectures incorporating a spirooxindole motif with excellent stereoselectivity.

Phosphine-catalysed asymmetric dearomative formal [4+2] cycloadditions of 3-benzofuranyl vinyl ketones.

In contrast to the catalytic asymmetric dearomative reactions of indole substrates, those of the analogous benzofuran derivatives have been less explored. Here we report that the stereoselective domino Rauhut-Currier/Michael addition process of 3-benzofuranyl vinyl ketones and 3-olefinic (7-aza)oxindoles can be realised via catalysis by a chiral bifunctional phosphine, furnishing the previously unreported direct asymmetric dearomative reaction of benzofuran substrates tethered to a carbonyl group in a formal [4+2] cycloaddition manner. An array of hydrodibenzofuran derivatives with dense substitutions is generally constructed with excellent diastereoselectivity and enantioselectivity (up to >19 : 1 dr, >99% ee).

Asymmetric Reactions involving Lewis Base Catalyst Tethered Dearomatized Intermediates.

Numerous protocols have been developed for the functionalization of aromatic substances. Among them, the strategy by which aromatic substrates are activated in situ to generate dearomatized intermediates is highly efficient but challenging, especially in the field of asymmetric catalysis. In this Concept article, the application of some well-established chiral Lewis base catalysis, including primary/secondary amines and N-heterocyclic carbenes, that can covalently form catalyst-tethered dearomatized ortho/para-quinodimethane species with diverse heteroaryl and aryl carbonyl substrates is summarized in a number of asymmetric cycloaddition and addition reactions with diverse reagents generally having electrophilic properties. As a result, a variety of enantioenriched aromatic products with higher molecular complexity are constructed effectively through a rearomatization process.

Asymmetric Dearomative Formal [4 + 2] Cycloadditions of N,4-Dialkylpyridinium Salts and Enones To Construct Azaspiro[5.5]undecane Frameworks.

The asymmetric dearomative formal [4 + 2] cycloaddition reaction of activated N,4-dialkylpyridinium salts and acyclic α,ß-unsaturated ketones was developed by the cascade iminium ion-enamine catalysis of a cinchona-derived amine. A spectrum of valuable azaspiro[5.5]undecane architectures was efficiently constructed with high to excellent diastereoselectivity and enantioselectivity.

Interrupted Morita-Baylis-Hillman-Type Reaction of α-Substituted Activated Olefins.

It was demonstrated that 3-olefinic oxindoles could generate zwitterionic enolate species with tertiary phosphines and undergo C-C bond formation with various electrophiles in an interrupted Morita-Baylis-Hillman-type reaction manner, followed by a dephosphoration process. Although the in situ formation of phosphorus-ylide intermediates was observed, no Wittig reaction was detected, even in the presence of excess formaldehyde. Moreover, excellent enantioselectivity for the construction of quaternary stereogenic centers was induced with chiral phosphines. Deuterium experiments and density functional theory calculations were conducted to elucidate the reaction mechanism.

Asymmetric Benzylic Functionalizations of 3-Vinyl Benzofurans via Cascade Formal Trienamine-Vinylogous Iminium Ion Activation.

An efficient approach to construct chiral 1,1-disubstituted ethane derivatives is presented. This strategy relies on the formation of the key dearomatizative vinylogous iminium ion species through protonation of the formal trienamine intermediates between 2-(3-vinylbenzofuran-2-yl)ethan-1-ones and a chiral primary amine. An array of nucleophiles, including 4-hydroxycoumarins, indoles, etc., have been effectively assembled at the benzylic site, delivering the expected 1,1-disubstituted ethane products in moderate to excellent enantioselectivity.