Electrocyclization‐Mediated Approach to 2‐Methyltriclisine, an Unnatural Analog of the Azafluoranthene Alkaloid Triclisine

Abstract

The synthesis of 2‐methyltriclisine, an unnatural analog of the azafluoranthene alkaloid triclisine, is reported. The synthesis was achieved in 10 steps and 21 % overall yield from 2‐bromo‐3,4‐dimethoxybenzaldehyde, through the intermediacy of 3,4‐dimethoxyfluoren‐9‐one. Construction of the heterocyclic ring entailed the para‐Claisen rearrangement of an allyl‐4‐fluorenyl ether, followed by isomerization of the resulting 2‐allylfluoren‐9‐one and a microwave‐assisted electrocyclization of the aza 6π‐electron system formed by oximation of its carbonyl function. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Palladium‐Catalyzed Direct Oxidative CH Cross‐Coupling of Azoarenes with Alcohols

“…We also ran the ortho ‐regioselective CH oxidative cross‐coupling of azoarene 1a with (2‐bromophenyl)methanol 2p under our reaction conditions, and got the acylated intermediate 3 ‐ 2p in 60% yield (Scheme ). Then a subsequent Pd‐catalyzed intramolecular cyclocoupling reaction20 of 3 ‐ 2p could further furnish the corresponding azofluorenone 4 , which has potential use as a promising industrial dye or non‐linear optical device 15d,f…”

Concise Synthesis of the ABC-Ring System of the Azafluoranthene, Tropoisoquinoline and Proaporphine Alkaloids: An Olefin Hydroacylation/Pomeranz–Fritsch Cyclization Approach

“…18 The azafluoranthenes, tropoisoquinolines and proaporphines share a tricyclic cyclopenta[ij]isoquinoline framework. We have previously disclosed an electrocyclizationmediated approach to 2-methyltriclisine, an unnatural analogue of the azafluoranthene alkaloid triclisine, 19 as well as modified Pomeranz-Fritsch cyclization-mediated syntheses of the ABC ring system of the related stephaoxocane alkaloids, 20a and other alternatives affording analogues of the latter. 20b-e In pursuit of our efforts towards the preparation of analogues of isoquinoline-type natural products, herein we wish to report a hydroacylation/Pomeranz-Fritsch cyclization approach for the synthesis of the ABC ring system characteristic of the azafluoranthene, tropoisoquinoline, and proaporphine alkaloids.…”

Divergent Total Syntheses to Azafluor­anthene and Dehydroaporphine Alkaloids

“…[8] Their wide range of biological activities has stimulated chemists to develop some methodologies to synthesize aporphine alkaloids, and various successful synthetic routes have been reported. [9] A number of different synthesis strategies have been devised for azafluoranthenes, which include microwave-assisted direct arylation of phenyltetrahydroisoquinolines, [10] electrocyclization-mediated approach, [11] combined aza-Wittig/electrocyclic ring closure/ intramolecular oxidative biaryl coupling, [12] ortho-and remote metalation/cross coupling, [13] utilization of the inverse-electron-demand Diels-Alder reactions of 3-methoxycarbonyl-2-pyrones, [14] Pschorr-based cyclization, [15] and photocyclization. [16] As part of our efforts to develop a new approach for the aporphine alkaloids, we developed a facile strategy that could be applicable for the synthesis of both azafluoranthene and aporphine alkaloids, and the details are reported herein.…”