Iron‐Carbonyl‐Catalyzed Redox‐Neutral [4+2] Annulation of N−H Imines and Internal Alkynes by C−H Bond Activation

Abstract

Stoichiometric C-H bond activation of arenes mediated by iron carbonyls was reported by Pauson as early as in 1965, yet the catalytic C-H transformations have not been developed. Herein, an iron-catalyzed annulation of N-H imines and internal alkynes to furnish cis-3,4-dihydroisoquinolines is described, and represents the first iron-carbonyl-catalyzed C-H activation reaction of arenes. Remarkablely, this is also the first redox-neutral [4+2] annulation of imines and alkynes proceeding by C-H activation. The reaction also features only cis stereoselectivity and excellent atom economy as neither base, nor external ligand, nor additive is required. Experimental and theoretical studies reveal an oxidative addition mechanism for C-H bond activation to afford a dinuclear ferracycle and a synergetic diiron-promoted H-transfer to the alkyne as the turnover-determining step.

Iron‐Catalyzed C−C Bond Formation via Chelation‐Assisted C−H Activation

“…Inspired by the seminal study on the Fe(0)‐mediated imine cyclometalation (Scheme ), Wang and coworkers discovered an Fe(0)‐catalyzed redox‐neutral annulation reaction between an aromatic N−H imine and a diaryl alkyne to produce 3,4‐dihydroisoquinoline derivative (Scheme ) . The reaction was achieved using Fe 3 (CO) 12 as a catalyst in Et 2 O at an elevated temperature of 120 °C, diastereoselectively affording the cis ‐isomer of dihydroisoquinoline derivative.…”

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

“…Daher ist anzunehmen, dass eine Allenspezies ein wichtiges Zwischenprodukt in dieser Tr ansformation sein kçnnte und dass die N-H-Imingruppe eine entscheidende Rolle fürd ie selektive intramolekulare Cyclisierung spielt. [13] Darüber hinaus wurden Syntheseanwendungen dieser Methode demonstriert. Dies bedeutet, dass die intramolekulare Cyclisierung vermutlich ein nukleophiler Additionsprozess ist.…”

“…Schließlich ergibt eine selektive intramolekulare Cyclisierung von IV das gewünschte Isochinolin 3a. [13] Darüber hinaus wurden Syntheseanwendungen dieser Methode demonstriert. Isochinolone sind unentbehrliche und ubiquitäre Strukturmotive in bioaktiven Verbindungen und Naturstoffen.…”

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

“…First, no oxidative annulation product was detected when N-phenyl-2-pyridinamine (4a)w as employed, and the skipped diene 5a was isolated instead in moderate yield (Scheme 5a). [13] Thes ynthetic application of our developed method was also demonstrated. This result revealed that an allene species might be akey intermediate,and that the N À Himine directing group plays ac rucial role for the selective intramolecular cyclization.A dditionally,n oc hirality transfer was observed when chiral carbonate (S)-2e(98 % ee)was applied, even when the reaction was conducted at al ower reaction temperature (80 8 8C; Scheme 5b).…”

“…Finally,ahighly selective intramolecular cyclization of IV would give the desired isoquinoline 3a. [13] Thes ynthetic application of our developed method was also demonstrated. Isoquinolones are indispensable and ubiquitous structural motifs in bioactive compounds and natural products.…”