A photoredox-catalyzed C–H functionalization of heteroarenes using a variety of primary, secondary, and tertiary alkyltrifluoroborates is reported. Using Fukuzumi's organophotocatalyst and a mild oxidant, conditions amenable for functionalizing complex heteroaromatics are described, providing a valuable tool for late-stage derivatization. The reported method addresses the three major limitations of previously reported photoredox-mediated Minisci reactions: (1) use of superstoichiometric amounts of a radical precursor, (2) capricious regioselectivity, and (3) incorporation of expensive photocatalysts. Additionally, a number of unprecedented, complex alkyl radicals are used, thereby increasing the chemical space accessible to Minisci chemistry. To showcase the application in late-stage functionalization, quinine and camptothecin analogues were synthesized. Finally, NMR studies were conducted to provide a rationalization for the heteroaryl activation that permits the use of a single equivalent of radical precursor and also leads to enhanced regioselectivity. Thus, by 1H and 13C NMR a distinct heteroaryl species was observed in the presence of acid catalyst and BF3.

/pdf/metal-free-c-h-alkylation-of-heteroarenes-with-52ryz54wbt.pdf

Metal-free C-H Alkylation of Heteroarenes With Alkyltrifluoroborates: A General Protocol for 1°, 2° and 3° Alkylation

An efficient one-pot synthesis of isoquinolines and heterocycle-fused pyridines by three-component reaction of aryl ketones, hydroxylamine, and alkynes is developed. The reaction involves condensation of aryl ketones and hydroxylamine, rhodium(III)-catalyzed C–H bond activation of the in situ generated aryl ketone oximes, and cyclization with internal alkynes. This protocol enables rapid assembly of multisubstituted isoquinolines as well as γ-carbolines, furo[2,3-c]pyridines, thieno[2,3-c]pyridines, and benzofuro[2,3-c]pyridines from readily available substrates.

Synthesis of isoquinolines and heterocycle-fused pyridines via three-component cascade reaction of aryl ketones, hydroxylamine, and alkynes.

An ammonium acetate assisted gold-catalyzed cascade cyclization reaction of 2-alkynylarylketones is described. Under the reported conditions, a gold-catalyzed intramolecular cyclization of 2-alkynylarylketones takes place through two competing reaction mechanisms—a 5-exo-dig or a 6-endo-dig cyclization—leading to two regioisomeric intermediates: isobenzofuranium or isobenzopyrylium. In the presence of ammonium acetate, the two intermediate compounds undergo further rearrangement to 2,3-disubstituted indenones and 1,3-disubstituted isoquinolines, respectively. While both reaction pathways proceed via a cyclization–rearrangement cascade, the gold-mediated 5-exo-dig process is especially notable, as it provides a novel cyclization protocol of 2-alkynylarylketones.

Gold-Catalyzed Ammonium Acetate Assisted Cascade Cyclization of 2-Alkynylarylketones.

Efficient synthesis of isoquinolines in water by a Pd-catalyzed tandem reaction of functionalized alkylnitriles with arylboronic acids

Cerium(III) salts have recently gained increasing attention in the synthetic community, owing to the powerful features that are reviewed in detail in this tutorial. This review reports significant examples of cerium(III) promoted synthesis of heterocyclic structures, initially dealing with the synthesis of five- and six-membered ring nitrogen containing heterocycles, then describing the preparation of their oxygenated analogues and finally discussing the achievement of seven-membered rings and mixed heterocyclic motifs.

Construction of heterocyclic structures by trivalent cerium salts promoted bond forming reactions

A palladium-catalyzed microwave-assisted one-pot reaction for the synthesis of isoquinolines is developed. The reaction is carried out by sequential coupling–imination–annulation reactions of ortho-bromoarylaldehydes and terminal alkynes with ammonium acetate, and a variety of substituted isoquinolines, furopyridines, and thienopyridines is prepared in moderate to excellent yields (up to 86%).

Microwave-assisted one-pot synthesis of isoquinolines, furopyridines, and thienopyridines by palladium-catalyzed sequential coupling-imination-annulation of 2-bromoarylaldehydes with terminal acetylenes and ammonium acetate.

A wide range of isoquinolines and related heterocyclic systems can be prepared starting from aldehyde substrates.

Microwave‐Assisted One‐Pot Synthesis of Isoquinolines, Furopyridines, and Thienopyridines by Palladium‐Catalyzed Sequential Coupling—Imination—Annulation of 2‐Bromoarylaldehydes with Terminal Acetylenes and Ammonium Acetate.

Using escape from conditioned aversive stimuli as an indirect index of strength of classical conditioning, one-trial conditioning was demonstrated. Electroconvulsive shock immediately following the unconditioned stimulus (footshock) yielded amnesia for the conditioned associations, and a single “reminder” footshock given in an environment dissimilar to the training apparatus restored memory in both between- and within-subjects designs. These results are inconsistent with the view that recovery induced by a noncontingent reminder shock from experimental amnesia depends upon classically conditioned associations that survive treatment by amnestic agents.

/pdf/ecs-induced-amnesia-and-recovery-of-memory-for-classically-3lmvkmwb9e.pdf

David Daniel

Papers

Microwave-assisted one-pot synthesis of isoquinolines, furopyridines, and thienopyridines by palladium-catalyzed sequential coupling-imination-annulation of 2-bromoarylaldehydes with terminal acetylenes and ammonium acetate.

Microwave‐Assisted One‐Pot Synthesis of Isoquinolines, Furopyridines, and Thienopyridines by Palladium‐Catalyzed Sequential Coupling—Imination—Annulation of 2‐Bromoarylaldehydes with Terminal Acetylenes and Ammonium Acetate.

ECS-induced amnesia and recovery of memory for classically conditioned fear in the rat