Indolizidine system

It is clear from the foregoing that ring closure to five-membered rings fused to the isoxazolidine, regardless whether part of a pyrrolizidine or of an indolizidine system, led mainly to the cis-anti isomers (see 243 a, b and 246 a, b)... 

Reactions where the reduction of a functionalized nitrogen, or the deprotection of an amine group, start a domino process with the sequential formation of the two rings of the indolizidine system, find many examples in the literature. A recent one is provided by the synthesis of (—)-indolizidine 223AB <20040L1493> (Scheme 10). 

Oxidation of (—)-tylocrebrine (3) and (—)-septicine by X-bromosuccinimide leads to aromatization of the six-membered ring of the indolizidine system. Thus (—)-tylocrebrine (3) is converted into the iminium salt (4), which is reduced by sodium borohydride to give ( )-tylocrebrine in high yield.3... 

The indolizidine systems of the thermodynamically more stable isomers have a chair form for ring C with C-9-H axial and trans to the lone pair orbital on the nitrogen and at each C-8 center C-8-H is axial and the bulky system linked through the carbonyl group is equatorial. 

The alternative route to (+)-swainsonine by Chen and Tsai used a very similar strategy, but instead formed the indolizidine system by making the C-8/C-8a bond (Scheme 87). In this case the amine 647 and commercially available 2,3-isopropyhdene-D-ribono-1,4-lactone (648) were condensed to form an amide, the terminal diol unit of which was cleaved with lead tetraacetate to give the 5-hydroxypyrroHdinone (—)-649 after acid-promoted cyclization. The thionocarbonate derivative (—)-650 was then treated with iodobenzene bis(trifluoroacetate) to deprotect the acylsi-lane. Intermediate (—)-651 then underwent radical-induced cyclization with tributyltin hydride to give the 8-hydroxyindolizidin-3-one 652 in... 

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