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.
Kaden
Silvia
S
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, D-14195 Berlin, Germany.
Reissig
Hans-Ulrich
HU
D002384:Catalysis; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry
C098358:FR 901483; D009943:Organophosphorus Compounds; D013141:Spiro Compounds; C099015:azaspirane