Palladium-catalyzed enantioselective β-hydride elimination for the construction of remote stereocenters.

The β-H elimination is a crucial elementary step in transition-metal catalysis, but controlling the stereochemistry of this process has been underdeveloped. The limited works reported so far have only focused on creating axial chirality in allenes, and no report has been able to build central chirality using asymmetric β-H elimination. In this study, we report a Trost ligand-enabled enantioselective desymmetric β-H elimination reaction from π-allyl-Pd.

Building Three-Dimensional Complexity by Intramolecular 2-Aminoallyl Cation-Diene (4+3) Cycloaddition.

Reliable methods for rapidly constructing C(sp)-rich three-dimensional polycycles are in high demand for organic synthesis and medicinal chemistry. Although there are various mature systems for synthesizing five- or six-membered polycycles, a catalytic platform for accessing diverse cycloheptanoid-containing polycyclic scaffolds is lacking. Herein, we describe a method for copper-catalyzed intramolecular 2-aminoallyl cation-diene (4+3) cycloaddition reactions.

Design, Preparation, and Implementation of Axially Chiral Benzotetramisoles as Lewis Base Catalysts for Asymmetric Cycloadditions.

Developing novel catalysts with potent activity is of great importance in organocatalysis. In this study, we designed and prepared a new class of benzotetramisole Lewis base catalysts (AxBTM) that have both central and axial chirality. This unique feature of these catalysts results in a three-dimensional microenvironment with multi-layers of chirality.

Synergistic Palladium/Copper-Catalyzed 1,4-Difunctionalization of 1,3-Dienes for Stereodivergent Construction of 1,5-Nonadjacent Stereocenters.

The construction of two distal stereocenters through a single catalytic process is of great interest in organic synthesis. While there are some successful reports regarding stereodivergent preparation of 1,3- or 1,4-stereocenters, the more challenged 1,5-nonadjacent stereocenters have never been achieved in a stereodivergent fashion. Herein we describe a synergistic palladium/copper catalysis for 1,4-difunctionalization reactions of 1,3-dienes, providing access to 1,5-nonadjacent quaternary stereocenters.

Synergistic Catalysis Involving Palladium for Stereodivergent Csp3-Csp3 Coupling Reactions.

ConspectusTransition-metal-catalyzed coupling reactions of dienes (such as 1,3-dienes, alkoxyallenes, and aminoallenes) with carbon nucleophiles have proven to be a highly effective method for creating Csp3-Csp3 bonds. These reactions have perfect atom economy and typically occur under mild reaction conditions. By using chiral metal complexes as catalysts, it is possible to create enantioenriched molecules bearing allylic stereocenters with high enantioselectivities.

Palladium-Catalyzed Enantioselective Hydrohydrazonation of 1,3-Dienes.

We presented a method for synthesizing allylic chiral hydrazones from 1,4-disubstituted 1,3-dienes and hydrazones through a ()-DTBM-Segphos-Pd(0)-catalyzed hydrohydrazonation reaction. This transformation has a wide range of substrates and good functional group tolerance. The desired products were obtained in medium to high yield and good regio- and enantioselectivity.

Copper-Catalyzed Enantioselective C1,N-Dipolar (3+2) Cycloadditions of 2-Aminoallyl Cations with Indoles.

2-Aminoallyl cations are versatile 1,3-dipoles that could potentially be used for diverse (3+n) cycloaddition reactions. Despite some preliminary studies, the asymmetric catalytic transformation of these species is still underdeveloped. We herein report a binuclear copper-catalyzed generation of 2-aminoallyl cations from ethynyl methylene cyclic carbamates and their enantioselective (3+2) cycloaddition reaction with indoles to construct chiral pyrroloindolines.

Stereodivergent Construction of Csp -Csp Bonds Bearing Vicinal Stereocenters by Synergistic Palladium and Phase-Transfer Catalysis.

Synergistic catalysis has emerged as one of the most powerful tools for stereodivergent formation of Csp -Csp bonds bearing vicinal stereocenters. Despite the many successes that have been achieved in this field, stereodivergent Csp -Csp coupling reactions involving stabilized nucleophiles remain challenging because of the competing single-catalysis pathway. Herein, we report a synergistic palladium/phase-transfer catalyst system that enables diastereodivergent Csp -Csp coupling reactions of 1,3-dienes with stabilized nucleophile oxindoles.

Carboxylic Acid-Directed Manganese(I)-Catalyzed Regioselective Hydroarylation of Unactivated Alkenes.

A carboxylic acid-directed regioselective hydroarylation reaction of unactivated alkenes with aryl boronic acids was reported. This transformation was enabled by homogeneous manganese catalyst MnBr(CO) in the presence of KOH and HO in the -xylene reaction medium. Both internal and terminal alkenes worked well in this transformation, and a series of functional groups were tolerated.

Enantioselective Three-Component Photochemical 1,4-Bisalkylation of 1,3-Butadiene with Pd/Cu Catalysis.

Catalysis by excited-state palladium has emerged as an active area of research, but controlling the enantioselectivity remains a challenge. Herein, we report the use of synergistic Pd/Cu catalysis to accomplish the first three-component photochemical 1,4-bisalkylation reactions of 1,3-butadiene. Consequently, α-amino acid esters bearing quaternary stereocenters were expeditiously synthesized from three simple starting materials: an alkyl bromide, butadiene, and an aldimine ester.

Diastereodivergent Aldol-Type Coupling of Alkoxyallenes with Pentafluorophenyl Esters Enabled by Synergistic Palladium/Chiral Lewis Base Catalysis.

As a fundamental and synthetically useful C-C bond formation reaction, the aldol reaction is one of the most versatile transformations in organic synthesis. However, despite extensive research on asymmetric versions of the reaction, a unified method for stereoselective access to the complementary syn and anti diastereomeric products remains to be developed. In this study, we developed a synergistic palladium/chiral Lewis base system that overcomes the inherent diastereoselectivity bias of aldol reactions and, as a result, allowed us to achieve the first diastereodivergent coupling reactions of alkoxyallenes with pentafluorophenol esters.

Synergistic Pd/Cu-catalyzed enantioselective Csp-F bond alkylation of fluoro-1,3-dienes with aldimine esters.

Due to high bond dissociation energies of Csp-F bonds, using fluorinated compounds in Csp-Csp cross-coupling is difficult. Here the authors report a protocol for enantioselective Csp-Csp coupling of dienyl fluorides with aldimine esters, enabled by synergistic copper and palladium catalysis. This reaction represents the first example of asymmetric Csp-Csp cross-coupling involving an inert Csp-F bond and provides expeditious access to chiral α-alkenyl α-amino acids with high enantioselectivity.

A Unified and Desymmetric Approach to Chiral Tertiary Alkyl Halides.

Enantioenriched tertiary alkyl halides are prevalent in bioactive molecules and can serve as versatile synthetic intermediates to construct complex structures. While conventional access to these motifs often hinges on stereoselective carbon-halogen or carbon-carbon bond formation reactions, desymmetric approaches using halogenated and prochiral tetrasubstituted carbons are largely elusive in comparison. Here, we report that a suite of dinuclear zinc catalysts with a prolinol- or pipecolinol-derived tetradentate ligand can reductively desymmetrize a large collection of easily available halomalonic esters to α-halo-β-hydroxyesters.

Synergistic Pd/Amine-Catalyzed Stereodivergent Hydroalkylation of 1,3-Dienes with Aldehydes: Reaction Development, Mechanism, and Stereochemical Origins.

Metal-hydride-catalyzed hydroalkylation of 1,3-dienes with enolizable carbonyl compounds is an atom- and step-economical method for preparing chiral molecules with allylic stereocenters. Although high diastereo- and enantioselectivities have been achieved for many coupling partners, aldehydes have not yet been used for this purpose because they are less stable than other carbonyl compounds under basic conditions and they have the potential to rapidly epimerize at the α-position. Moreover, stereodivergent hydroalkylation reactions of 1,3-dienes to access complementary diastereomers with vicinal stereocenters is challenging.

Gold-Catalyzed Formal Hexadehydro-Diels-Alder/Carboalkoxylation Reaction Cascades.

A dual gold-catalyzed hexadehydro-Diels-Alder/carboalkoxylation cascade reaction is reported. In this transformation, the gold catalyst participated in the hexadehydro-Diels-Alder step, switching the mechanism from a radical type to a cationic one, and then the catalyst activated the resulting aryne to form an ortho-Au phenyl cation species, which underwent a carboalkoxylation rearrangement rather than the expected aryne-ene reaction.

Lewis-Acid-Promoted Ligand-Controlled Regiodivergent Cycloaddition of Pd-Oxyallyl with 1,3-Dienes: Reaction Development and Origins of Selectivities.

For nearly 30 years, considerable research effort has been focused on the development of methods for catalytic (3 + 2) cycloaddition reactions of palladium-oxyallyl species with alkenes. However, because C-O bond formation is kinetically favored, the (3 + 2) cycloadditions achieved to date have involved C-O reductive elimination. We herein report a method of lithium triflate-promoted (3 + 2) cycloaddition reactions of palladium-oxyallyl species with 1,3-dienes that proceed via a pathway terminated with C-C bond formation to give a five-membered carbocycle.

Enantioselective Inverse Electron Demand (3 + 2) Cycloaddition of Palladium-Oxyallyl Enabled by a Hydrogen-Bond-Donating Ligand.

Cycloaddition reactions between oxyallyl cations and alkenes are important transformations for the construction of ring systems. Although (4 + 3) cycloaddition reactions of oxyallyl cations are well-developed, (3 + 2) cycloadditions remain rare, and an asymmetric version has not yet been developed. Moreover, because oxyallyl cations are highly electrophilic, only electron-rich olefins can be used as cycloaddition partners.

Diastereodivergent Synthesis of β-Amino Alcohols by Dual-Metal-Catalyzed Coupling of Alkoxyallenes with Aldimine Esters.

Both syn- and anti-β-amino alcohols are common structural motifs in natural products, drug molecules, chiral ligands and catalysts. However, the currently available methods for synthesizing these motifs are limited to generate only one diastereoisomer. Therefore, development of a unified method for stereoselective access to complementary diastereomers would be highly desirable.

Palladium-Catalyzed Regio- and Enantioselective Hydrosulfonylation of 1,3-Dienes with Sulfinic Acids: Scope, Mechanism, and Origin of Selectivity.

Chiral sulfones are important structural motifs in organic synthesis because of their widespread use in pharmaceutical chemistry. In particular, chiral allylic sulfones have drawn particular interest because of their synthetic utility. However, enantioselective synthesis of 1,3-disubstituted unsymmetrical chiral allylic sulfones remains a challenge.

Stereodivergent Coupling of 1,3-Dienes with Aldimine Esters Enabled by Synergistic Pd and Cu Catalysis.

Herein we describe the use of synergistic Pd and Cu catalysis for stereodivergent coupling reactions between 1,3-dienes and aldimine esters. By using different enantiomers of the two metal catalysts, all four stereoisomers of the coupling products, which have two vicinal stereocenters, could be accessed with high diastereo- and enantioselectivity. This atom-economical cross-coupling reaction has a wide substrate scope and good functional group tolerance.

Rhenium-Catalyzed Intramolecular Carboalkoxylation and Carboamination of Alkynes for the Synthesis of C3-Substituted Benzofurans and Indoles.

A rhenium-catalyzed carboalkoxylation and carboamination of alkyne is reported. This reaction provides an efficient route to synthesize de novo C3-substituted benzofurans and indoles under mild conditions in moderate to good yields. Mechanistic studies revealed that the rhenium played the role of a π acid catalyst to activate the alkynes, followed by a charge-accelerated [3,3]-sigmatropic rearrangement.

Enantioselective and Regioselective Hydroetherification of Alkynes by Gold-Catalyzed Desymmetrization of Prochiral Phenols with P-Stereogenic Centers.

The gold(I)-catalyzed enantioselective hydroetherification of alkynes was achieved via desymmetrization of prochiral bisphenols bearing P-stereogenic centers. ( S)-DTBM-Segphos(AuCl)/AgNTf proved to be a highly efficient catalyst system for this transformation, affording P-chiral cyclic phosphine oxides in good yields with high enantioselectivities (with up to 99% ee). The same catalyst system allowed for the enantioselective desymmetrization of dialkynes.

Dual Gold-Catalyzed Formal Tetradehydro-Diels-Alder Reactions for the Synthesis of Carbazoles and Indolines.

This work reports a dual gold-catalyzed tetradehydro-Diels-Alder reaction for the synthesis of nitrogen-containing aromatic heterocycles. Under the catalytic system (IPrAuNTf /DIPEA), indolines and carbazoles as well as other N-containing aromatic heterocycles were prepared in high yields with good functional group tolerance. Unlike the traditional thermal tetradehydro-Diels-Alder reactions, diluted reaction concentration and radical prohibitors are not required for this protocol.

De Novo Synthesis of Phenols and Naphthols through Oxidative Cycloaromatization of Dienynes.

In this work, a rhodium-catalyzed oxidative cycloaromatization of dienynes, which provides a highly straightforward and efficient way to access polysubstituted naphthols and phenols under mild conditions, is described. Challenged electron-withdrawing groups are well tolerated in this protocol, and late-stage phenyl ring formation is demonstrated.

Recent advances in enantioselective gold catalysis.

Interest in homogeneous gold catalysis has undergone a marked increase. As strong yet air- and moisture-tolerant π-acids, cationic gold(i) complexes have been shown to catalyze diverse transformations of alkenes, alkynes and allenes, opening new opportunities for chemical synthesis. The development of efficient asymmetric variants is required in order to take full advantage of the preparative potential of these transformations.