A Straightforward and Efficiently Scaleable Synthesis of Novel Racemic 4-Substituted-2,8-diazaspiro[4.5]decan-1-one Derivatives

Abstract

Novel and straightforward syntheses (3-5 steps, high yields) of racemic diazaspiropiperidine derivatives based on the Michael addition of pipecolate-derived enolates to a range of nitroalkenes have been developed. The reaction has been shown to have a general scope and can be conducted on a preparatively useful scale. Isolation and identification of diazaspiropiperidine enantiomers was efficiently achieved using normal phase chiral HPLC.

Key words

cyclizations - lactams - Michael additions - piperidines - spiro compounds

References

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  1-Phenyl-1,3,8-triaza­-spiro[4.5]decan-4-one is commercially available (Fluka, Acros).

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9

Reduction using H₂ (1 atm), Pd/C in EtOH, Fe/AcOH or SnCl₂ in HCl-mediated reduction resulted in the formation of complex mixtures with the major component being the incompletely reduced hydroxylamine derivatives and their subsequent spiro-cyclized products.