Rhodium(III)‐Catalyzed Intramolecular Redox‐Neutral Annulation of Tethered Alkynes: Formal Total Synthesis of (±)‐Goniomitine

Abstract

A Rh(III)-catalyzed intramolecular redox-neutral atom-economic annulation of a tethered alkyne has been developed to efficiently construct 2-amidealkyl indoles with completely reversed regioselectivity by a C-H activation pathway. Furthermore, using the Rh(III)-catalyzed C-H activation/annulation as a key step, a one-pot synthesis of pyrido[1,2-a]indoles has also been developed and applied to a highly efficient formal total synthesis of (±)-goniomitine.

A Fischer Indolization Strategy toward the Total Synthesis of (–)-Goniomitine

“…Flash column chromatography (SiO 2 , 15% EtOAc in hexanes) afforded DHPI 7 (158 mg, 33% yield) as an orange oil: R f = 0.3 (3:2 hexanes:Et 2 O eluent); spectroscopic data were consistent with those reported in the literature. 15 …”

Rh(III)- and Ir(III)-Catalyzed C–C Bond Cross Couplings from C–H Bonds

“…were designed and applied in redox-neutral couplings with alkynes [49][50][51][52][53][54]. In addition, an intramolecular version of this transformation was used as a key step allowing construction of indolizidine-based natural products like (AE)-antofine and (AE)-septicine [55] and (AE)-goniomitine, bearing a pyrido [1,2-a] indole core [56,57] (3).…”

Mechanistic Investigation into RhIII‐Catalyzed Intramolecular Redox‐Neutral Annulation of Aryl Hydrazines with a Tethered Alkyne

“…Recently, Li et al. successfully developed a metal‐catalyzed intramolecular cyclization strategy for an alkyne‐tethered phenylhydrazine to prepare 2‐amidealkyl‐substituted indoles that could be readily transformed into biologically active pyrido[1,2‐ a ]indole scaffolds.…”

“… Rh III ‐catalyzed intramolecular redox‐neutral annulation of alkyne‐tethered phenylhydrazine according to Li and co‐workers …”

“… Plausible pathway proposed by Li and co‐workers for the Rh III ‐catalyzed intramolecular redox‐neutral annulation of alkyne‐tethered phenylhydrazine.…”