ABSTRACT
Background Tashiromine (1) is a naturally occurring indolizidine, isolated from an Asian deciduous shrub Maackia tashiroi. [1] As one of the structurally simpler indolizidine alkaloids, [2] tashiromine has been a popular target for synthetic chemists, and to date has succumbed to total synthesis on thirteen occasions. [3-15] A wide variety of reactions have been employed to assemble the core indolizidine structure, including radical cyclisations;[3] nucleophilic addition to imines;[5,14,15] electrophilic alkylation of pyrroles;[7,13] alkylation of enamines,[6] β-amino esters [8] and pyrrolidinyllithiums;[12] stereoselective reduction of enamines [4,9] and pyridinium salts; [11] and titanium-mediated reductive imide-olen cyclisation. [10] Our own approach [14] utilises an intramolecular addition of an allylsilane to an N-acyliminium ion to deliver the [4.3.0]-azabicyclic (indolizidine) skeleton 2 (Scheme 1), wherein the pendant vinyl group acts as a handle to install the hydroxymethyl sidechain found in tashiromine. e synthesis of azabicyclic assemblies by intramolecular allylsilane/N-acyliminium cyclisations was rst studied by Hiemstra and Speckamp,[16] who prepared their functionalised allylsilane cyclisation precursors (such as 3) by alkylation of cyclic imides with reagent 4 (X = OMs). is, in turn, was prepared in four steps by alkylation of an acetylide anion with commercially available iodomethyltrimethylsilane, followed by partial reduction of the alkyne. Alternative synthetic approaches to 4 (X = OMs, I) involve olenation of aldehydes using the Seyferth-Fleming phosphorane [17] or nickel-catalysed 1,2-metallate rearrangement of lithiated dihydropyran. [18] Our approach was informed by the prior work by our own group [19-24] and others [25-38] on the use of olen metathesis to generate functionalised allylsilanes.
