Diastereo‐ and Enantioselective 1,4‐Difunctionalization of Borylenynes by Catalytic Conjunctive Cross‐Coupling

Enantioselective conjunctive cross‐coupling of enyne‐derived boronate complexes occurs with 1,4 addition of the electrophile and migrating group across the π system. This reaction pathway furnishes α‐boryl allenes as the reaction product. In the presence of a chiral catalyst, both the central and axial chirality of the product can be controlled during product formation.     

Catalytic Enantioselective Synthesis of anti-Vicinal Silylboronates by Conjunctive Cross-Coupling

Chiral 1,2-bimetallic reagents are useful motifs in synthetic chemistry. Although syn-1,2-bimetallic compounds can be prepared by alkene dimetallation, anti-1,2-bimetallics are still rare. The stereospecific 1,2-metallate shift that occurs during conjunctive cross-coupling is shown to enable a practical and modular approach to the catalytic synthesis of enantioenriched anti-1,2-borosilanes. In addition to reaction development, the synthetic utility of anti-1,2-borosilanes was investigated, including applications to the synthesis of anti-1,2-diols and anti-1,2-amino alcohols     

Enantioselective Construction of Tertiary Boronic Esters by Conjunctive Cross‐Coupling

Catalytic enantioselective conjunctive cross‐coupling has been developed to construct tertiary alkylboronic esters. These reactions occur with good yield and enantioselectivity for a range of substrates. Mechanistic experiments reveal aspects of the catalytic cycle that allow hindered substrates to react without significant complicating side reactions.     

Enantioconvergent Fukuyama Cross‐Coupling of Racemic Benzylic Organozinc Reagents

The first enantioconvergent palladium‐catalyzed Fukuyama cross‐coupling of racemic benzylic organozinc reagents with thioesters has been developed. The reaction furnishes enantioenriched acyclic α‐disubstituted ketone products in good yields and high enantioselectivities. A broad substrate scope is achieved under mild reaction conditions to prevent racemization of the potentially labile tertiary stereocenters.     

Synthesis and Functionalization of Allenes by Direct Pd‐Catalyzed Organolithium Cross‐Coupling

A palladium‐catalyzed cross‐coupling between in situ generated allenyl/propargyl‐lithium species and aryl bromides to yield highly functionalized allenes is reported. The direct and selective formation of allenic products preventing the corresponding isomeric propargylic product is accomplished by the choice of SPhos or XPhos based Pd catalysts. The methodology avoids the prior transmetalation to other transition metals or reverse approaches that required prefunctionalization of substrates with leaving groups, resulting in a fast and efficient approach for the synthesis of tri‐ and tetrasubstituted allenes. Experimental and theoretical studies on the mechanism show catalyst control of selectivity in this allene formation.     

Diastereo- and Enantioselective 1,4-Difunctionalization of Borylenynes by Catalytic Conjunctive Cross-Coupling

Enantioselective conjunctive cross-coupling of enyne-derived boronate complexes occurs with 1,4 addition of the electrophile and migrating group across the π system. This reaction pathway furnishes α-boryl allenes as the reaction product. In the presence of a chiral catalyst, both the central and axial chirality of the product can be controlled during product formation.     

A Polystyrene‐Cross‐Linking Tricyclohexylphosphine: Synthesis,Characterization and Applications to Pd‐Catalyzed Cross‐Coupling Reactions of Aryl Chlorides

A polystyrene‐cross‐linking tricyclohexylphosphine (PS‐TCP) was synthesized through radical emulsion polymerization of 4‐tert‐butylstyrene as a monomer and tris(trans‐4‐styrylcyclohexyl)phosphine as a threefold cross‐linker. The PS‐TCP showed enhanced ligand performance compared to the corresponding polystyrene‐triphenylphosphine hybrid PS‐TPP and tricyclohexylphosphine in Pd‐catalyzed Suzuki–Miyaura and Buchwald–Hartwig reactions of aryl chlorides.     

Continuous‐Flow Synthesis of Biaryls by Negishi Cross‐Coupling of Fluoro‐ and Trifluoromethyl‐Substituted (Hetero)arenes

A continuous‐flow method for the regioselective arylation of fluoroarenes and fluoropyridines has been developed. The telescoped procedure reported here consists of a three‐step metalation, zincation, and Negishi cross‐coupling sequence, providing efficient access to a variety of functionalized 2‐fluorobiaryl products. Precise temperature control of the metalation step, made possible by continuous‐flow technology, allowed for the efficient preparation of the arylated products in high yields and short residence times. Additionally, several examples of the regioselective arylation of benzotrifluoride derivatives are also provided.     

Enantioselective Radical Addition/Cross‐Coupling of Organozinc Reagents,Alkyl Iodides,and Alkenyl Boron Reagents

A hybrid transition‐metal/radical process is described that results in the addition of organozinc reagents and alkyl halides across alkenyl boron reagents in an enantioselective catalytic fashion. The reaction can be accomplished both intermolecularly and intramolecularly, providing useful product yields and high enantioselectivities in both manifolds.     

Synthesis of Aryldifluoroamides by Copper‐Catalyzed Cross‐Coupling

A copper‐catalyzed coupling of aryl, heteroaryl, and vinyl iodides with α‐silyldifluoroamides is reported. The reaction forms α,α‐difluoro‐α‐aryl amides from electron‐rich, electron‐poor, and sterically hindered aryl iodides in high yield and tolerates a variety of functional groups. The aryldifluoroamide products can be transformed further to provide access to a diverse array of difluoroalkylarenes, including compounds of potential biological interest.     

Palladium‐Catalyzed Oxygenative Cross‐Coupling of Ynamides and Benzyl Bromides by Carbene Migratory Insertion

A palladium‐catalyzed oxygenative cross‐coupling of ynamides and benzyl bromides has been developed. After subsequent hydrogenation, α,α‐disubstituted amide derivatives were obtained in good yields. Migratory insertion of α‐oxo palladium carbene species, generated by intermolecular oxidation, is proposed as the key step in this reaction. The study demonstrates the potential of ynamides to serve as carbene precursors in palladium‐catalyzed C?C bond‐forming cross‐coupling reactions.     

Iridium‐Catalyzed Enantioselective Allyl–Allylsilane Cross‐Coupling

An enantioselective allyl–allylsilane cross‐coupling involving racemic branched allylic alcohols and allylsilanes is reported. An iridium‐(P,olefin) phosphoramidite complex enables the transformation with high regio‐ and stereoselectivity under operationally simple conditions. The utility of the coupling is demonstrated in a concise catalytic, enantioselective synthesis of a pyrethroid insecticide protrifenbute.     

Palladium‐Catalyzed Cross‐Coupling of Alkenyl Carboxylates

Carboxylate esters have many desirable features as electrophiles for catalytic cross‐coupling: they are easy to access, robust during multistep synthesis, and mass‐efficient in coupling reactions. Alkenyl carboxylates, a class of readily prepared non‐aromatic electrophiles, remain difficult to functionalize through cross‐coupling. We demonstrate that Pd catalysis is effective for coupling electron‐deficient alkenyl carboxylates with arylboronic acids in the absence of base or oxidants. Furthermore, these reactions can proceed by two distinct mechanisms for C?O bond activation. A Pd^0/II catalytic cycle is viable when using a Pd⁰ precatalyst, with turnover‐limiting C?O oxidative addition; however, an alternative pathway that involves alkene carbopalladation and β‐carboxyl elimination is proposed for Pd^II precatalysts. This work provides a clear path toward engaging myriad oxygen‐based electrophiles in Pd‐catalyzed cross‐coupling.     

Synthesis of Biaryl‐Bridged Cyclic Peptides via Catalytic Oxidative Cross‐Coupling Reactions

Biaryl‐bridged cyclic peptides comprise an intriguing class of structurally diverse natural products with significant biological activity. Especially noteworthy are the antibiotics arylomycin and its synthetic analogue G0775, which exhibits potent activity against Gram‐negative bacteria. Herein, we present a simple, flexible, and reliable strategy based on activating‐group‐assisted catalytic oxidative coupling for assembling biaryl‐bridged cyclic peptides from natural amino acids. The synthetic approach was utilized for preparing a number of natural and unnatural biaryl‐bridged cyclic peptides, including arylomycin/G0775 and RP 66453 cyclic cores.     

Enantioselective Construction of α‐Chiral Silanes by Nickel‐Catalyzed C(sp3)−C(sp3) Cross‐Coupling

An enantioselective C(sp³)?C(sp³) cross‐coupling of racemic α‐silylated alkyl iodides and alkylzinc reagents is reported. The reaction is catalyzed by NiCl₂/(S,S)‐Bn‐Pybox and yields α‐chiral silanes with high enantiocontrol. The catalyst system does not promote the cross‐coupling of the corresponding carbon analogue, corroborating the stabilizing effect of the silyl group on the alkyl radical intermediate (α‐silicon effect). Both coupling partners can be, but do not need to be, functionalized, and hence, even α‐chiral silanes with no functional group in direct proximity of the asymmetrically substituted carbon atom become accessible. This distinguishes the new method from established approaches for the synthesis of α‐chiral silanes.     

Nickel‐Catalyzed Enantioselective Conjunctive Cross‐Coupling of 9‐BBN Borates

Catalytic enantioselective conjunctive cross‐coupling between 9‐BBN borate complexes and aryl electrophiles can be accomplished with Ni salts in the presence of a chiral diamine ligand. The reactions furnish chiral 9‐BBN derivatives in an enantioselective fashion and these are converted to chiral alcohols and amines, or engaged in other stereospecific C−C bond forming reactions.     

Reductive Cross‐Coupling of Conjugated Arylalkenes and Aryl Bromides with Hydrosilanes by Cooperative Palladium/Copper Catalysis

A method for the reductive cross‐coupling of conjugated arylalkenes and aryl bromides with hydrosilanes by cooperative palladium/copper catalysis was developed, thus resulting in the highly regioselective formation of various 1,1‐diarylalkanes, including a biologically active molecule. Under the applied reaction conditions, high levels of functional‐group tolerance were observed, and the reductive cross‐coupling of internal alkynes with aryl bromides afforded trisubstituted alkenes.     

One‐Pot Tandem Photoredox and Cross‐Coupling Catalysis with a Single Palladium Carbodicarbene Complex

The combination of conventional transition‐metal‐catalyzed coupling (2 e^? process) and photoredox catalysis (1 e^? process) has emerged as a powerful approach to catalyze difficult cross‐coupling reactions under mild reaction conditions. Reported is a palladium carbodicarbene (CDC) complex that mediates both a Suzuki–Miyaura coupling and photoredox catalysis for C?N bond formation upon visible‐light irradiation. These two catalytic pathways can be combined to promote both conventional transition‐metal‐catalyzed coupling and photoredox catalysis to mediate C?H arylation under ambient conditions with a single catalyst in an efficient one‐pot process.     

Tandem Chemoselective Suzuki–Miyaura Cross‐Coupling Enabled by Nucleophile Speciation Control

Control of boronic acid speciation is presented as a strategy to achieve nucleophile chemoselectivity in the Suzuki–Miyaura reaction. Combined with simultaneous control of oxidative addition and transmetalation, this enables chemoselective formation of two C? C bonds in a single operation, providing a method for the rapid preparation of highly functionalized carbogenic frameworks.