Project description:Organic-solvent-free cross-couplings between benzylic and alkenyl halides have been developed. Various alkenyl halides can be efficiently benzylated by combining the precursor halides in the presence of Zn dust and a Pd catalyst at room temperature, in water as the only medium.
Project description:Herein, a facile and general electroreductive deuteration of unactivated alkyl halides (X = Cl, Br, I) or pseudo-halides (X = OMs) using D2O as the economical deuterium source was reported. In addition to primary and secondary alkyl halides, sterically hindered tertiary chlorides also work very well, affording the target deuterodehalogenated products with excellent efficiency and deuterium incorporation. More than 60 examples are provided, including late-stage dehalogenative deuteration of natural products, pharmaceuticals, and their derivatives, all with excellent deuterium incorporation (up to 99% D), demonstrating the potential utility of the developed method in organic synthesis. Furthermore, the method does not require external catalysts and tolerates high current, showing possible use in industrial applications.
Project description:The pervasive occurrence of saturated stereogenic carbon centers in pharmaceuticals, agrochemicals, functional organic materials, and natural products has stimulated great efforts toward the construction of such saturated carbon centers. We report a reaction mode for the enantioselective construction of alkyl-alkyl bond to access saturated stereogenic carbon centers by asymmetric reductive cross-coupling between different alkyl electrophiles in good yields with great levels of enantioselectivity. This reaction mode uses only alkyl electrophiles for enantioselective Csp3-Csp3 bond-formation, rendering reductive alkyl-alkyl cross-coupling as an alternative to traditional alkyl-alkyl cross-coupling reactions between alkyl nucleophiles and alkyl electrophiles to access saturated stereogenic carbon centers without the use of organometallic reagents. The reaction displays a broad scope for two alkyl electrophiles with good functional group tolerance. Mechanistic studies reveal that the reaction undergoes a single electron transfer that enabled the reductive coupling pathway to form the alkyl-alkyl bond.
Project description:A method for asymmetric alkyl-alkyl Suzuki reactions of unactivated secondary alkyl electrophiles, specifically, cross-couplings of racemic acylated halohydrins with alkylborane reagents, has been developed. A range of protected bromohydrins, as well as a protected chlorohydrin and a homologated bromohydrin, are coupled in good ee by a catalyst derived from commercially available components.
Project description:Polyfluoroarene moieties are of interest in medicinal chemistry, agrochemicals, and material sciences. Herein, we present the first polyfluoroarylation of unactivated alkyl halides via a halogen atom transfer process. This method converts primary, secondary, and tertiary alkyl halides into the respective polyfluoroaryl compounds in good yields in the presence of amide, carbamate, ester, aromatic, and sulfonamide moieties, including derivatives of complex bioactive molecules. Mechanistic work revealed that this transformation proceeds through an alkyl radical generated after the halogen atom transfer.
Project description:A catalytic C-H alkylation using unactivated alkyl halides and a variety of arenes and heteroarenes is described. This ring-forming process is successful with a variety of unactivated primary and secondary alkyl halides, including those with β-hydrogens. In contrast to standard polar or radical cyclizations of aromatic systems, electronic activation of the substrate is not required. The mild, catalytic reaction conditions are highly functional group tolerant and facilitate access to a diverse range of synthetically and medicinally important carbocyclic and heterocyclic systems.
Project description:The development of a nickel-catalyzed C-H alkylation of aromatic substrates with unactivated alkyl halides is described. This carbocyclization facilitates the synthesis of diverse fused ring systems from simple aromatic substrates and is an attractive alternative to traditional polar or radical-mediated ring formations. The present system uses unactivated primary and secondary alkyl bromides and chlorides, while avoiding the use of precious palladium catalysts and more reactive alkyl halides commonly used in related C-H alkylations.
Project description:A method for the cross-coupling of alkyl electrophiles with various potassium aryl- and heteroaryltrifluoroborates has been developed. Nearly stoichiometric amounts of organoboron species could be employed to cross-couple a large variety of challenging heteroaryl nucleophiles. Several functional groups were tolerated on both the electrophilic and the nucleophilic partners. Chemoselective reactivity of C(sp(3))-Br bonds in the presence of C(sp(2))-Br bonds was achieved.
Project description:A highly chemoselective iron-catalyzed three-component dicarbofunctionalization of unactivated olefins with alkyl halides (iodides and bromides) and sp2-hybridized Grignard reagents is reported. The reaction operates under fast turnover frequency and tolerates a diverse range of sp2-hybridized nucleophiles (electron-rich and electron-deficient (hetero)aryl and alkenyl Grignard reagents), alkyl halides (tertiary alkyl iodides/bromides and perfluorinated bromides), and unactivated olefins bearing diverse functional groups including tethered alkenes, ethers, protected alcohols, aldehydes, and amines to yield the desired 1,2-alkylarylated products with high regiocontrol. Further, we demonstrate that this protocol is amenable for the synthesis of new (hetero)carbocycles including tetrahydrofurans and pyrrolidines via a three-component radical cascade cyclization/arylation that forges three new C-C bonds.