Natural products swainsonine

This method was adapted towards the synthesis of the natural product swainsonine which closely resembles l,2,3,5,6,8a-hexahydroindolizine (1). 

This synthesis of (-)-swainsonine involves 21 steps and proceeds with an overall yield of 6.6% from tran5-l,4-dichloro-2-butene. It is not only the first reported noncarbohydrate route to this natural product, but it allows the stereoselective access to all 16 epimers and/or enantiomers of swainsonine as well. 

It is well known that alkyl azides also behave as 1,3-dipoles in intramolecular thermal cycloaddition reactions. The formation of two carbon-nitrogen bonds leads to triazolines, which are usually not stable. They decompose after the loss of nitrogen to aziridines, diazo compounds, and heterocyclic imines. There are a limited number of examples reported in which the triazoline was isolated [15]. The dipolar cycloaddition methodology has been extremely useful for the synthesis of many natural products with interesting biological activities [16], In recent years, the cycloaddition approach has allowed many successful syntheses of complex molecules which would be difficult to obtain by different routes. For instance, Cha and co-workers developed a general approach to functionalized indolizidine and pyrrolizidine alkaloids such as (-i-)-crotanecine [17] and (-)-slaframine [18]. The key step of the enantioselective synthesis of (-)-swainsonine (41), starting from 36, involves the construction of the bicyclic imine 38 by an intramolecular 1,3-dipolar cycloaddition of an azide derived from tosylate 36, as shown in Scheme 6 [ 19). 

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