Application of a Raney-Cobalt-Mediated Tandem Reductive Cyclization Protocol to Total Syntheses of the Aspidosperma Alkaloids (±)-Limaspermidine and (±)-1-Acetylaspidoalbidine

Abstract

The racemic modification of the Aspidosperma alkaloid limaspermidine (1) has been prepared in ten steps including one involving a Raney-cobalt-mediated tandem reductive cyclization of nitrile 8 to give the tetracyclic system 9b. Compound (±)-1 has been converted over two steps into (±)-1-acetylaspidoalbidine [(±)-13].

Total Synthesis of (±)‐1‐Acetylaspidoalbidine and (±)‐1‐Methylaspidospermidine

“…However, it was this last step that had delayed the completion of the total synthesis for about one year. As pointed out by Banwell, [9] the conversion reported by Ban [5b, 12] et al encountered difficulties in our synthesis. Many other reaction conditions that seemed to work well for the oxidation of other architectures containing a tertiary amine [13] did not work.…”

“…Recently, Banwell reported a concise total synthesis [9] of acetylaspidoalbidine that is strategically more convergent than the previous ones.…”

Synthesis of Spirocyclic Indolenines

“…Inspired by this approach, Kwon and co‐workers implemented this strategy in their synthesis of (+)‐ibophyllidine, utilising a similar telescoped spirocyclisation‐aza‐Baylis–Hillman reaction sequence to afford the pentacyclic skeleton 144 (a precursor to (+)‐ibophyllidine) in excellent yield . Banwell and co‐workers also used a AgOTf promoted alkylation of 145 in their total synthesis of (±)‐limaspermidine and (±)‐1‐acetylaspidoalbidine precursor 146 . Shao, Peng and co‐workers have also applied this strategy in natural product synthesis, to form similar pentacyclic frameworks 148 and 150 in good yields .…”

“…and (AE)-1-acetylaspidoalbidine precursor 146. [95] Shao, Peng and co-workers have also applied this strategy in natural product synthesis, to form similar pentacyclic frameworks 148 and 150 in good yields. [96,97] Finally Weinreb and co-workersr eported the cyclopropanation spirocyclisation of 151,w hich upon treatment with either AgOTf or AgBF 4 ,a fforded the spirocyclic indolenine 152 in excellent yield.…”

A Chemoenzymatic Route to the (+)-Form of the Amaryllidaceae Alkaloid Narseronine

“…Various manipulations of this last compound including the Raney-cobalt mediated reduction of the associated nitrile residue [9,11] afforded, over eight steps and in 16 % overall yield, the a-arylated cyclohexenone 8 carrying a protected secondary amine residue tethered through the g-carbon. Finally, treatment of compound 8 with (Ph 3 P) 4 Pd in the presence of dimedone resulted in cleavage of the Alloc group, thus allowing the resulting secondary amine 9 (which was not isolated) to undergo an intramolecular hetero-Michael addition reaction/ trans-acylation sequence and so affording (À)-narseronine [(À)-1] (82 %), the structure of which was secured by singlecrystal X-ray analysis.…”