Azetidines are receiving much attention as building blocks in medicinal chemistry. Whilst many examples are based on 3-substituted azetidine scaffolds which are inherently achiral, access to larger regions of chemical space would be possible if efficient access to chiral 2-substituted azetidines could be achieved. Currently, there are only a very limited number of methods for the asymmetric synthesis of such materials. Here we report use of Enders’ SAMP/RAMP methodology to develop a general one-pot asymmetric synthesis of 2-substituted azetidin-3-ones in high yield and enantioselectivity.<br/><br/>In a separate strand of work, we report the synthesis of spirocyclic 1,2-diazetidines containing a second nitrogen atom. Copper catalysed ring closure of 2-bromo-2-propenyl hydrazines readily provides methylene 1,2-diazetidines. Further reactions with carbenes provides access to a range of diazaspiro[2.3]hexanes in up to 97% yield.

Stereocontrolled synthesis of 2-substituted azetidines and spirocyclic 1,2-diazetidines

254th National Meeting (2017)

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