Efficient Approach to the Azaspirane Core of FR 901483

[reaction: see text] An efficient approach to the azaspirane core of FR 901483 is described employing lithiated methoxyallene as a crucial C3 building block and a suitably protected enantiopure ketimine as the second component. The resulting dihydropyrrole derivative was smoothly converted into a spiro keto aldehyde which under acidic conditions provided a novel azanorbornane derivative 15. Under basic reaction conditions, the desired 5-azatricyclo[6.3.1.0(1,5)]dodecane skeleton 16 was generated. The ratio of diastereomers strongly depends on the reaction conditions employed with l-proline in DMSO providing the highest selectivity in favor of one azaspirane product.