Formal Aromatic C−H Insertion for Stereoselective Isoquinolinone Synthesis and Studies on Mechanistic Insights into the C−C Bond Formation

Abstract

Formal aromatic C-H insertion of rhodium(II) carbenoid was intensively investigated to develop a new methodology and probe its mechanism. Contrasting with the previously proposed direct C-H insertion, the mechanism was revealed to be electrophilic aromatic substitution, which was supported by substituent effects on the aromatic ring and a secondary deuterium kinetic isotope effect. Various isoquinolinones were synthesized intramolecularly via six-membered ring formation with high regio- and diastereoselectivity, while averting the common Buchner-type reaction. Intermolecularly, dirhodium catalyzed formal aromatic C-H insertion on electron-rich aromatics was also achieved.

Intramolecular Aromatic Carbenoid Insertion of Biaryldiazoacetates for the Regioselective Synthesis of Fluorenes

“…[5] As an alternative approach to synthesize the fluorene skeleton, an intramolecular aromatic carbenoid insertion can be regarded as a facile route to form a 5,6-bicyclic ring system. [6,7] In fact, this strategy was elegantly utilized in the preparation of (hetero)aromatic bicyclic ring systems, although the reaction efficiency fluctuates depending on the substrate type and reaction conditions. With regard to this aspect, the synthesis of fluorenes was previously achieved with a benzylic carbene intermediate in 1958 by Denney and Klemchuk, [8] in which 2-phenylphenyldiazomethane was used as a precursor for the photolytic ring-forming reaction.…”

Carbenes and Nitrenes

“…Formation of isoquinolinone by rhodium-catalysed aromatic C-H insertion has been shown to be highly dependent on the Y substituents of the starting diazo compounds (66). 107 Indeed isoquinoline has been exclusively observed for Y = SO 2 Ph or P(O)(OEt) 2 supporting (together with a secondary deuterium kinetic isotope effect) an electrophilic aromatic substitution mechanism.…”

Ruthenium‐Catalyzed Coupling of Oxabenzonorbornadienes with Alkynes Bearing a Propargylic Oxygen Atom: Access to Stereodefined Benzonorcaradienes

“…[23] The diastereoselectivity of the coupling depends on the presence of the substituents at bridgehead positions of oxabenzonorbornadienes. To the best of our knowledge, this unusual coupling reaction, related to the Büchner reaction [24,25] of naphthalene, is unprecedented. Further investigations are underway to elucidate the effect of the substituents at bridgehead positions on the diastereoselectivity of the coupling.…”