Facile Synthesis of Phenanthridinone Alkaloids via Suzuki–Miyaura Cross‐coupling

Abstract

Phenanthridinone alkaloids crinasiadine 1 and N‐alkylcrinasiadines 6, 7, 8, 9, 10 have been synthesized based on palladium‐catalyzed tandem C–C and C–N bond formation starting from 2‐aminophenylboronic acid and 2‐bromobenzoate in short steps. Related alkaloids, 5,6‐dihydrobicolorine 2, trisphaeridine 3, and bicolorine 12 have also been synthesized.

Synthetic Strategies in the Preparation of Phenanthridinones

“…Later, Tanimoto et al established a convenient one-step access to biologically important phenanthridinones 14 using 2-halobenzoate 12 and 2-aminophenylboronic acid 13 in a Suzuki-Miyaura cross-coupling reaction with palladium(II) acetate and 2-dicyclohexylphosphino-2 ,6 -dimethoxybiphenyl (SPhos) as precatalysts (Scheme 6) [78]. Interestingly, Kuwata et al extended this strategy to synthesize the phenanthridinone alkaloids crinasiadine and N-alkylcrinasiadines from 2-aminophenylboronic acid and 2-bromobenzoate [79]. Furthermore, 2-halobenzoates were proved to be an efficient substrate for preparing biologically active phenanthridinones [80][81][82].…”

A Review on Recent Syntheses of Amaryllidaceae Alkaloids and Isocarbostyrils (Time period mid-2016 to 2017)

“…Tanimori and coworkers extended their developed protocol for the synthesis of some new phenanthridone alkaloids via Suzuki-Miyaura cross-coupling in the following way [52]. Reaction between ester 199 and 2aminobenzeneboronic acid catalysed by Pd…”

“…The Ts group was then removed by sodium naphthalide at -78 °C, followed by a Pictet-Spengler cyclisation with formalin to produce the all-important 5,11methanomorphanthridine-3-one 286 (40% for the two steps), which represents the basic scaffold of the montanine alkaloids (Scheme 48). vi) Synthesis of phenanthridinone alkaloids via Suzuki-Miyaura cross-coupling, by Tanimori and co-workers: Tanimori and coworkers extended their developed protocol for the synthesis of some new phenanthridone alkaloids via Suzuki-Miyaura cross-coupling in the following way [52]. Reaction between ester 199 and 2aminobenzeneboronic acid catalysed by Pd(OAc) 2 , (S)-phos and viii) Total syntheses of zephycandidine III and lycosinine A, by Banwell and co-workers: Banwell and co-workers, after failing to form the important aryl-aryl bond between two relevant precursors for their synthesis of the two Amaryllidacea alkaloids zephycandidine III, 298 and lycosinine A 272 via the anticipated Suzuki-Miyaura cross coupling protocol, resorted to the palladiumcatalysed Ullmann cross coupling which proved more successful [54].…”

Nickel-Catalyzed Oxidative Decarboxylative Annulation for the Synthesis of Heterocycle-Containing Phenanthridinones

“…Phenanthridinones are key structures found in a variety of natural products and biologically active compounds 1 including antiviral and anticancer therapeutics 2 , aurora kinase 3 and polymerase (PARP) inhibitors 4 as well as serve as important building blocks toward complex polycyclic targets. 5 The corresponding heterocycle-containing phenanthridinones, however, are less-explored due, in part, to a shortage of efficient synthetic routes to these compounds.…”

“…Typically, construction of these scaffolds 7,8 relies on traditional cross-coupling reactions, 3 such as Suzuki-Miyaura coupling (Scheme 1, eq 1) or Buchwald-Hartwig amination reactions. 9 These methods, however, require prefunctionalized aryl halide and arylboronic ester or acid coupling partners.…”