Search for: All records

Abstract Carbosulfenylation of olefins represents an important class of reactions for the synthesis of structurally diverse organosulfur compounds. Previous studies typically yield 1,2‐regioselectivity. In the context of diversity‐oriented synthesis, accessing the regioreversed products is desirable, significantly broadening the scope of these reactions. In this study, we report a nickel‐catalyzed 2,1‐carbosulfenylation of trifluoromethyl‐ andgem‐difluoroalkenes, using free thiols and benzyl bromides as sulfur and carbon sources, respectively. The unusual regioselectivity observed is enabled by a “radical sorting” mechanism. The Ni catalyst activates benzyl bromide to generate a benzylic radical that undergoes hydrogen atom transfer (HAT) with the thiol to form a sulfur‐centered radical. The sulfur radical subsequently adds to the fluoroalkenes, resulting in an α‐fluoroalkyl C‐radical. This radical undergoes S_H2 with a Ni–CH₂Ar to form a C(sp³)─C(sp³) bond and quaternary center, ultimately producing valuable fluoroalkyl thioethers. Isotopic labeling experiments corroborate a hydrogen atom transfer (HAT) event within the working mechanism. 

Abstract Alkynyl amides play crucial roles in organic synthesis in the production of bioactive compounds and valuable heterocycles. Despite numerous studies on their synthesis, challenges persist due to the necessity of harsh or hazardous conditions and the use of costly or unstable reagents. Herein, we present a one‐pot method for the synthesis of all three bonds of the alkyne under transition‐metal‐free conditions. An important feature of this chemistry is the use of readily available feedstock chemicals, such as methyl esters and acetamides. This approach offers efficient access to a wide range of aryl and alkyl alkynyl amides and demonstrates excellent tolerance towards various functional groups in a sustainable and cost‐effective manner. 

Abstract Rh(I)‐catalyzed C8‐selective C−H alkenylation and arylation of 1,2,3,4‐tetrahydroquinolines with alkenyl and aryl carboxylic acids under microwave assistance have been realized. Using [Rh(CO)₂(acac)] as the catalyst and Piv₂O as the acid activator, 1,2,3,4‐tetrahydroquinolines undergo C8‐selective decarbonylative C−H alkenylation with a wide range of alkenyl and aryl carboxylic acids, affording the C8‐alkenylated or arylated 1,2,3,4‐tetrahydroquinolines. This method enables the synthesis of C8‐alkenylated 1,2,3,4‐tetrahydroquinolines that would otherwise be difficult to access by means of conventional C−H alkenylation protocols. Moreover, this catalytic system also works well in C8‐selective decarbonylative C−H arylation of 1,2,3,4‐tetrahydroquinolines with aryl carboxylic acids. The catalytic activity strongly depends on the choice of theN‐directing group, with the readily installable and removableN‐(2‐pyrimidyl) group being optimal. The catalytic pathway is elucidated by mechanistic experiments. 

Abstract A base‐promoted net‐[3+2] cycloaddition of nitriles and 1‐arylpropynes for the synthesis of pyrroles is described. The developed method provides convenient access to various 2,5‐disubstituted or 2,4,5‐trisubstituted pyrroles in 40% to 96% yields (32 examples). Among methods for the synthesis of pyrroles, the protocol presented here stands out for its convenience and atom‐economy. 

Abstract A mild photoredox catalyzed construction of sulfides, disulfides, selenides, sulfoxides and sulfones from unstrained ketone precursors is introduced. Combination of this deacylative process with S_N2 or coupling reactions provides novel and convenient modular strategies toward unsymmetrical or symmetric disulfides. Reactivity studies favor a bromine radical that initiates a HAT (Hydrogen Atom Transfer) from the aminal intermediate resulting in expulsion of a C‐centered radical that is intercepted to make C−S and C−Se bonds. Gram scale reactions, broad substrate scope and tolerance towards various functional groups render this method appealing for future applications in the synthesis of organosulfur and selenium complexes. 

Abstract Aziridines are highly valued synthetic targets in organic and medicinal chemistry. The organocatalytic synthesis of such structures with broad substrate scope and good diastereoselectivity, however, is rare. Herein, we report a broadly applicable and diastereoselective synthetic method for the synthesis oftrans‐aziridines from imines and benzylic or alkyl halides utilizing sulfenate anions (PhSO^–) as the catalyst. Substrates bearing heterocyclic aromatic groups, alkyl, and electron‐rich and electron‐poor aryl groups were shown to be compatible with this method (33 examples), giving good yields and high diastereoselectivities (trans:cis>20 : 1). Further functionalization of aziridines containing cyclopropyl or cyclobutyl groups was achieved through ring‐opening reactions, with a cyclobutyl‐substituted norephedrine derivative obtained through a four‐step synthesis. We offer a mechanistic proposal involving reversible addition of the deprotonated benzyl sulfoxide to the imine to explain the hightrans‐diastereoselectivity. 

Abstract A novel, selective and high‐yielding palladium‐catalyzed carbonylative arylation of a variety of weakly acidic (pK_a25–35 in DMSO) benzylic and heterobenzylic C(sp³)−H bonds with aryl bromides has been achieved. This system is applicable to a range of pro‐nucleophiles for access to sterically and electronically diverse α‐aryl or α,α‐diaryl ketones, which are ubiquitous substructures in biologically active compounds. The Josiphos SL‐J001‐1‐based palladium catalyst was identified as the most efficient and selective, enabling carbonylative arylation with aryl bromides under 1 atm CO to provide the ketone products without the formation of direct coupling byproducts. Additionally, (Josiphos)Pd(CO)₂was identified as the catalyst resting state. A kinetic study suggests that the oxidative addition of aryl bromides is the turnover‐limiting step. Key catalytic intermediates were also isolated. 

Abstract α‐Amino nitriles are versatile structural motifs in a variety of biologically active compounds and pharmaceuticals and they serve as valuable building blocks in synthesis. The preparation of α‐ and β‐functionalized α‐amino nitriles from readily available scaffolds, however, remains challenging. Herein is reported a novel dual catalytic photoredox/copper‐catalyzed chemo‐ and regioselective radical carbocyanation of 2‐azadienes to access functionalized α‐amino nitriles by using redox‐active esters (RAEs) and trimethylsilyl cyanide. This cascade process employs a broad scope of RAEs and provides the corresponding α‐amino nitrile building blocks in 50–95 % yields (51 examples, regioselectivity >95 : 5). The products were transformed into prized α‐amino nitriles and α‐amino acids. Mechanistic studies suggest a radical cascade coupling process. 

The synthesis of enantioenriched aziridines is important for drug development due to their prevalence in bioactive molecules. Previous methods often use expensive catalysts, activated substrates, or show poor stereoselectivity. Herein,...