Synthesis of Intricate Fused N-Heterocycles via Ring-Rearrangement Metathesis

Abstract

Herein, a facile synthesis of intricate fused N-heterocycles is disclosed by employing C-H activation and ring-rearrangement metathesis/enyne ring-rearrangement metathesis as key steps. Interestingly, some of these N-heterocyclic products possess the tricyclic core of epimeloscine, deoxycalyciphylline B, daphlongamine H, isodaphlongamine H, and a bioactive alkaloid, annotinolide A, which shows antiaggregation activity against amyloid-β (Aβ) peptide aggregation. Moreover, various starting materials required in this protocol are easily assembled via C-X bond annulation of 2-bromo-N-protected aniline with norbornadiene or directing group-assisted ruthenium-catalyzed C-H activation of N-methoxybenzamide.

A Planar‐Chiral Rhodium(III) Catalyst with a Sterically Demanding Cyclopentadienyl Ligand and Its Application in the Enantioselective Synthesis of Dihydroisoquinolones

“…The synthesized products 6 h / 6 h′ are of interest as both of them have structures similar to narciclasine alkaloids . Compounds 6 n and 6 o can also be used for the synthesis of alkaloids by ring‐rearrangement metathesis …”

A Planar‐Chiral Rhodium(III) Catalyst with a Sterically Demanding Cyclopentadienyl Ligand and Its Application in the Enantioselective Synthesis of Dihydroisoquinolones

“…[31] Compounds 6n and 6o can also be used for the synthesis of alkaloids by ring-rearrangement metathesis. [32] Theb est alkene components are norbornene-type derivatives,which are readily available from Diels-Alder additions to cyclopentadiene and provide av ariety of options for further functionalization. Unstrained cyclic alkenes,s uch as cyclohexene,r eacted slowly with phenylhydroxamic acid (4) under our catalytic conditions,w hile upon heating, Lossen rearrangement became the dominant process (this typical problem has been observed previously with other rhodium catalysts).…”

“…In the case of meta-substituted aryl and 2-naphtyl hydroxamic acids,m ixtures of regioisomers were formed with 3:1-14:1 selectivity,which is similar or better to those provided by related achiral [(C 5 H 3 t Bu 2 )RhCl 2 ] 2 catalysts. [32] Theb est alkene components are norbornene-type derivatives,which are readily available from Diels-Alder additions to cyclopentadiene and provide av ariety of options for further functionalization. [31] Compounds 6n and 6o can also be used for the synthesis of alkaloids by ring-rearrangement metathesis.…”

Palladium‐Catalyzed Synthesis of Indolines from Aroyloxycarbamates through a Tandem Decarboxylative Amination/Heck/Annulation Reaction

“…As alkene is a reactive function group, the annulated indoline product can be transformed to several other products, such as indole, tricyclic indoline epoxide, and dihydroxylation products and can even be used as substrates in total synthesis . To demonstrate the potential utility of the indoline products, compounds…”

“…4,4 a,9,9 a‐tetrahydro‐1 H ‐1,4‐methanocarbazole ( 3 n ) . Brown solid (22.5 mg, 41%); mp: 62–65 °C; R f =0.3 (hexane:EtOAc=20:1); 1 H NMR (400 MHz, CDCl 3 ) δ 7.05 (d, J =7.3 Hz, 1H), 6.99 (t, J =7.6 Hz, 1H), 6.66 (t, J =7.3 Hz, 1H), 6.52 (d, J =7.8 Hz, 1H), 6.28 (dd, J =5.6, 3.0 Hz, 1H), 6.04 (dd, J =5.6, 3.0 Hz, 1H), 3.93 (d, J =8.1 Hz, 1H), 3.79 (br, 1H), 3.44 (d, J =8.0 Hz, 1H), 2.90 (s, 1H), 2.84 (s, 1H), 1.63 (d, J =9.0 Hz, 1H), 1.48 (d, J =9.0 Hz, 1H); 13 C NMR (101 MHz, CDCl 3 ) δ 154.2, 139.6, 135.4, 129.9, 127.7, 124.2, 118.2, 109.0, 64.1, 50.5, 50.4, 48.4, 42.3.…”