A modular total synthesis of (±)-trigonoliimine C

Abstract

A convergent total synthesis of trigonoliimine C has been executed by employing three catalytic transformations in sequence. The key reactions that have been developed in this context include the [Au]-catalyzed addition of protected tryptamine to isatogens and the reduction of N-OH to NH with hydrazine monohydrate.

Counterion Control oft‐BuO‐Mediated Single Electron Transfer to Nitrostilbenes to ConstructN‐Hydroxyindoles or Oxindoles

“…A solvent screen revealed that N-hydroxyindole formation occurred smoothly in ethereal solvents,b ut was attenuated in tert-butanol (entries 7-10). [11] To our surprise,t he identity of the counterion was critical to the reaction outcome:while no reaction was observed when lithium-or magnesium tertbutoxide was employed, 3-phenyl-3-hydroxy-2-oxindole 6a was obtained as the only product using potassium tertbutoxide irrespective of exposure to light (entries [11][12][13]. Thef ormation of 6a,w hose structure confirmed by X-ray crystallography, [12] involves not only oxygen transfer to the ortho-alkenyl substituent but also a[ 1,2]-phenyl shift.…”

“…Thef ormation of 6a,w hose structure confirmed by X-ray crystallography, [12] involves not only oxygen transfer to the ortho-alkenyl substituent but also a[ 1,2]-phenyl shift. While oxygen transfer from nitroarenes to pendant acetylenes has been reported to afford N-heterocycles, [13] this oxidationmigration tandem reaction of ortho-alkenyl substituents is unprecedented.…”

“…First, the success of the oxygen-transfer-migration reaction was less dependent on the electronic nature of the nitrostilbene with chloro-, bromo-and even trifluoromethyl groups tolerated (entries 2-10). Further,t he opposite electronic trend was observed for b-aryl groups:more electron-deficient groups led to higher oxindole yields (entries [11][12][13][14][15]. Naphthalene 2q demonstrated that oxindole formation tolerated an increased steric environment around the nitro-group to afford 6q albeit in diminished yield relative to 6a (entry 16).…”

Synthesis of the Azepinobisindole Alkaloid Iheyamine A Enabled by a Cross-Mannich Reaction

“…collected off Iheya Island, Okinawa . The iheyamines possess an intriguing azepinobisindole framework also present in the recently isolated natural product (−)-trigonoliimine C ( 3 ) (Figure ). Despite being isolated in 1999, Bremner’s attempted biomimetic synthesis of an iheyamine A model system remains the only report detailing synthetic efforts toward these alkaloids .…”

Asymmetric Synthesis of C2-Quaternary Indolin-3-ones Enabled by N-Heterocyclic Carbene Catalysis

“…Indolin-3-one with a quaternary stereocenter at the 2-position is frequently found as the privileged structure of numerous biologically active natural products and synthetic compounds (Figure ). Besides, C2-quaternary indolin-3-ones were usually used as important intermediates for natural product synthesis . Thus, the development of asymmetric synthetic approaches to access such valuable molecules has always been of interest among the scientific community .…”