Rh(iii)-catalyzed C–H activation/cyclization of oximes with alkenes for regioselective synthesis of isoquinolines

Abstract

A Rh(iii)-catalyzed C-H activation/cyclization of oximes and alkenes for facile and regioselective access to isoquinolines has been developed. This protocol features mild reaction conditions and easily accessible starting materials, and has been applied to the concise synthesis of moxaverine. A kinetic isotope effect study was conducted and a plausible mechanism was proposed.

Arylacetic Acids in Organic Synthesis

“…Among them, we mainly discussed about reactions triggered by six kinds of pathways: (1) acid as the directing group; (2) decarboxylation; (3) deprotonation; (4) nucleophilic methylenes; (5) nucleophilic acids; (6) electrophilic acids. Especially, nucleophilic methylenes, Friedel‐Crafts reaction, nucleophilic acids and electrophilic acids have been used in total synthesis of (−)‐pauciflorol F, moxaverine, (−)‐6‐O‐desmethylantofine and (+)‐6‐O‐desmethylantofine, derivate of salvianolic acid B, communesin F and perophoramidine, (+)‐O‐methylthalibrine, sparstolonin B, lennoxamine, chilenine, fumaridine, 8‐Oxypseudoplamatine, 2‐O‐methyloxyfagaronine, (S)‐equol, xiamenmycin A and (±)‐glabridin . However, challenges still existed: (1) C−N and C−X (X=F, Cl, Br, I) bond may be constructed simultaneously during one procedure by the aid of decarboxylation and formation of radicals; (2) Decarboxylative cross coupling or tandem applications with boron reagent, diazonium salt, 1,3‐dicarbonyls were anticipated; (3) The ketones from reactions of arylacetic acids with aryl acids may function as useful intermediates in tandem reactions and show their significances in construction of diverse heterocycles.…”

Redoxneutrale Mangan(I)‐katalysierte C‐H‐Aktivierung: regioselektive Anellierung mithilfe einer spurlosen dirigierenden Gruppe

“…Um die Verträglichkeit dieser Methode mit verbreiteten funktionellen Gruppen sowie Heterocyclen zu demonstrieren, wurde ein Robustness-Screen angewendet (Details siehe SI). [14] Diese Verbindungen konnten mithilfe Zusammenfassend wurde eine allgemeine und skalierbare Strategie entwickelt, um regioselektiv N-Heterocyclen unter Verwendung von Alkinkupplungspartnern mit einer spurlosen dirigierenden Gruppe und einem einfachen Katalysator auf Manganbasis zu synthetisieren. Die Reaktion beginnt mit der basenunterstützten Cyclomanganierung von Imin 1a unter Bildung eines fünfgliedrigen Manganacyclus I.Anschließend wird durch die Koordination des Carbonylsauerstoffatoms des Carbonats 2a an Intermediat I der Manganacyclus II gebildet, dem eine regioselektive Alkininsertion und anschließende selektive b-Sauerstoff-Eliminierung folgen.…”

“…[11] Darüber hinaus sind Isochinolin und seine Derivate übliche Motive in Wirk-und Naturstoffen wie der Antitumorverbindung PK11209, dem peripheren Benzodiazepinrezeptorliganden PK11195 und dem Naturstoff Moxaverin, der zur Behandlung funktioneller gastrointestinaler Stçrungen verwendet wurde. [14] Diese Verbindungen konnten mithilfe…”

Redox‐Neutral Manganese(I)‐Catalyzed C−H Activation: Traceless Directing Group Enabled Regioselective Annulation

“…[8] Furthermore,akinetic isotope effect (k H /k D = 1.62) was observed from two parallel reactions of 1aor [D]-1awith 2a (for details,see the Supporting Information). [14] Pleasingly,these compounds could be concisely prepared by using our Scheme 4. [12] On the basis of the aforementioned results and previous reports, [8,9] ap lausible mechanism was proposed (Scheme 6).…”

“…[11] Isoquinoline and its derivatives are also common motifs in pharmaceuticals and natural products,s uch as antitumor compound PK11209, the peripheral benzodiazepine receptor ligand PK11195, and the drug moxaverine,which was used to treat functional gastrointestinal disorders. [14] Pleasingly,these compounds could be concisely prepared by using our…”